survival

Clinical Efficacy of Daratumumab in Monotherapy of Relapsed/Refractory Multiple Myeloma

AUTOIMMUNE THROMBOCYTOPENIA , ,

SS Bessmeltsev1, EV Karyagina2, EYu Ilyushkina2, ZhL Stolypina2, RR Miftakhova1, II Kostroma1, TL Shelkovskaya2

1 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

2 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

For correspondence: Prof. Stanislav Semenovich Bessmeltsev, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-67-80, +7(911)228-18-01; e-mail: bsshem@hotmail.com, bessmeltsev@yandex.ru

For citation: Bessmeltsev SS, Karyagina EV, Ilyushkina EYu, et al. Clinical Efficacy of Daratumumab in Monotherapy of Relapsed/Refractory Multiple Myeloma. Clinical oncohematology. 2020;13(1):25–32. (In Russ).

DOI: 10.21320/2500-2139-2020-13-1-25-32

ABSTRACT

Background. Daratumumab is IgG1-κ humanized anti-CD38 monoclonal antibody. It has a direct impact on tumor and immunomodulatory effect.

Aim. To assess the efficacy of daratumumab monotherapy in patients with progressive, and relapsed/refractory multiple myeloma (MM), as well as to find out the degree of toxicity and safety of this drug.

Materials & Methods. The trial included 10 MM patients (3 men and 7 women) aged 51–74 years (median 57 years). Stage 3 (according to Durie-Salmon system) was determined in all patients, in 2 of them stage 3B with creatinine clearance < 30 mL/min was reported. According to ISS (International Staging System) criteria, stage 2 and stage 3 were identified in 6 and 4 patients, respectively. All the patients had been previously treated with bortezomib and lenalidomide with further double refractoriness in 4 out of 10 patients. Bendamustine and carfilzomib were administered to one patient each, both in combined regimens. The number of previous therapy lines was 3–6 (median 5).

Results. Overall response was 50 % including 2 (20 %) patients with very good partial remission. In 1 (10 %) patient complete remission was achieved. During the follow-up of 6–32 months (median 15 months) median overall survival was not achieved. Median progression-free survival was 17.8 months. Daratumumab is characterized by favorable safety profile. In 20 % of patients infusion-induced reactions with severity grades 1–2 were observed. Among other adverse events the following should be pointed out: weakness (30 %), nausea (10 %), headache (10 %), anorexia (10 %), thrombocytopenia (20 %), and neutropenia (30 %). No serious complications were reported.

Conclusion. Daratumumab treatment is a safe and effective method of anticancer drug therapy in relapsed/refractory MM.

Keywords: daratumumab, multiple myeloma, complete remission, overall response, survival, double refractoriness.

Received: August 22, 2019

Accepted: December 10, 2019

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REFERENCES

  1. Бессмельцев С.С., Абдулкадыров К.М. Множественная миелома: руководство для врачей. М.: СИМК, 2016. 512 с.

    [Bessmeltsev SS, Abdulkadyrov KM. Mnozhestvennaya mieloma: rukovodstvo dlya vrachei. (Multiple myeloma: manual for physicians.) Moscow: SIMK Publ.; 2016. 512 p. (In Russ)]

  2. Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsed after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. 2012;26(1):149–57. doi: 10.1038/leu.2011.196.

  3. Usmani S, Ahmadi T, Ng Y, et al. Analysis of Real-World Data on Overall Survival in Multiple Myeloma Patients With ≥ 3 Prior Lines of Therapy Including a Proteasome Inhibitor (PI) and an Immunomodulatory Drug (IMiD), or Double Refractory to a PI and an IMiD.  2016;21(11):1–7. doi: 10.1634/theoncologist.2016-0104.

  4. Terpos E, Kanellias N, Christoulas D, et al. Pomalidomide: a novel drug to treat relapsed and refractory multiple myeloma. OncoTargets Ther. 2013;6:531–8. doi: 10.2147/OTT.S34498.

  5. Семочкин С.В., Салогуб Г.Н., Бессмельцев С.С., Капланов К.Д. Практические аспекты применения карфилзомиба при множественной миеломе. Клиническая онкогематология. 2019;12(1):21–31. doi: 10.21320/2500-2139-2019-12-1-21-31.

    [Semochkin SV, Salogub GN, Bessmeltsev SS, Kaplanov KD. Practical Aspects of the Use of Carfilzomib in Multiple Myeloma. Clinical oncohematology. 2019;12(1):21–31. doi: 10.21320/2500-2139-2019-12-1-21-31. (In Russ)]

  6. Moreau P, Masszi T, Grzasko N, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374(17):1621–34. doi: 10.1056/nejmoa1516282.

  7. San Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomized, open-label, phase 3 trial. Lancet Oncol. 2013;14(11):1055–66. doi: 10.1016/s1470-2045(13)70380-2.

  8. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142–52. doi: 10.1056/nejmoa1411321.

  9. Бессмельцев С.С. Анти-CD38 моноклональные антитела в лечении рецидивов/рефрактерных форм множественной миеломы. Вестник гематологии. 2018;XIV(3):5–18.

    [Bessmeltsev SS. CD38 antibodies in patients with relapsed/refractory multiple myeloma. Vestnik gematologii. 2018; XIV(3):5–18. (In Russ)]

  10. Deckert J, Wetzel MC, Bartle LM, et al. SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38 hematologic malignancies. Clin Cancer Res.  2014;20(17):4574–83. doi: 10.1158/1078-0432.CCR-14-0695.

  11. de Weers M, Tai YT, van der Veer MS, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol.  2011;186(3):1840–8. doi: 10.4049/jimmunol.1003032.

  12. van de Donk WCJ, Richardson P, Malavasi F. CD38 antibodies in multiple myeloma: back to the future. 2018;131(1):13–29. doi: 10.1182/blood-2017-06-740944.

  13. Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373(13):1207–19. doi: 10.1056/nejmoa1506348.

  14. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment refractory multiple myeloma (SIRIUS): an open-label, randomized, phase 2 trial.   2016;387(10027):1551–60. doi: 10.1016/s0140-6736(15)01120-4.

  15. Usmani SZ, Weiss BM, Plesner T, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma.   2016;128(1):37–44. doi: 10.1182/blood-2016-03-705210.

  16. Durie BGM, San Miguel J, Harousseau J-L, et al. International uniform response criteria for multiple myeloma. 2006;20(9):1467–73. doi: 10.1038/sj.leu.2404284.

  17. Головкина Л.Л., Минеева Н.В., Менделеева Л.П. и др. Модификация преаналитического этапа непрямой пробы Кумбса у больных множественной миеломой при лечении даратумумабом. Гематология и трансфузиология. 2018;63(1):44–54. doi: 10.25837/HAT.2018.45..1..004.

    [Golovkina LL, Mineeva NV, Mendeleeva LP, et al. A Modification of the pre-analytical phase of the indirect Coombs test for multiple myeloma patients treated with daratumumab. Russian journal of hematology and transfusiology. 2018;63(1):44–54. doi: 10.25837/HAT.2018.45..1..004. (In Russ)]

  18. Минеева Н.В., Кробинец И.И., Бодрова Н.Н. и др. Алгоритм индивидуального подбора гемокомпонентов и проведения исследования антигенов эритроцитов и антиэритроцитарных антител в сложно диагностируемых случаях. Методическое пособие. СПб.: ВиТ-принт, 2018. 24 с.

    [Mineeva NV, Krobinets II, Bodrova NN, et al. Algoritm individualnogo podbora gemokomponentov i provedeniya issledovaniya antigenov eritrotsitov i antieritrotsitarnykh antitel v slozhno diagnostiruemykh sluchayakh. Metodicheskoe posobie. (Algorithm of individual hemocomponent management and analysis of erythrocyte antigens and anti-erythrocyte antibodies used in difficult for diagnosis cases. Methodological handbook.) Saint Petersburg: ViT-print Publ.; 2018. 24 p. (In Russ)]

Primary Bone Lymphomas: 18F-FDG PET and PET-CT as Methods of Diagnosis and Efficacy Estimation of Antitumor Treatment

AUTOIMMUNE THROMBOCYTOPENIA , , ,

AK Smol’yaninova1, ER Moskalets2, GA Yatsyk1, IE Kostina1, AS Bogolyubskaya3, NG Gabeeva1, EG Gemdzhian1, SA Tatarnikova1, DS Badmadzhapova1, EE Zvonkov1

1 National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 European Medical Center, 35 Shchepkina str., Moscow, Russian Federation, 129090

3 NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

For correspondence: Anna Konstantinovna Smol’yaninova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(926)912-31-16; e-mail: annmo8@mail.ru

For citation: Smol’yaninova AK, Moskalets ER, Yatsyk GA, et al. Primary Bone Lymphomas: 18F-FDG PET and PET-CT as Methods of Diagnosis and Efficacy Estimation of Antitumor Treatment. Clinical oncohematology. 2020;13(1):33–49 (In Russ).

DOI: 10.21320/2500-2139-2020-13-1-33-49

ABSTRACT

Background. Primary bone lymphoma (PBL) is a rare malignant tumor. Initial examination aimed at detecting all primary lesions is an indispensable prerequisite for the choice of optimal antitumor treatment. Standard methods of diagnosis (X-ray, CT, and MRI) are not always adequate to measure the real tumor mass. Another well-known characteristic feature of PBL is a challenge in evaluating the effect of its treatment because of residual changes in the bones of most patients. However, the data on using 18F-FDG PET, another method of metabolic imaging, in PBL are rather rare in accessible literature.

Aim. To study the specific use of PET with 18F-FDG at initial examination and efficacy estimation of PBL treatment.

Materials & Methods. The trial included 21 PBL patients who received PET with 18F-FDG at initial examination and a month after the end of treatment. The results of 18F-FDG PET imaging were compared with the data obtained by means of structural diagnostic methods (CT and MRI) and the analysis of biopsy samples with pathologic lesions.

Results. Intensive uptake of 18F-FDG (SUVmax 8.6–40.1, mean SUVmax 23.5), according to PET data, was reported in all patients in those tumor lesions which were identified by the structural diagnostic methods and confirmed by biopsies. Besides, each of 21 cases showed pathologic infiltration of adjacent soft tissues with high metabolic activity. In PET-CT with 18F-FDG 13 further tumor localizations were revealed in 8 (38 %) patients. On completing the therapy, according to CT and MRI data, residual changes were observed in all (n = 21, 100 %) patients. The residual metabolic activity in the involved bones was identified in 13 (62 %) patients (SUVmax 2.91–8.7, mean SUVmax 4.2). In 4 of them the residual lesions were subjected to biopsy. None of 4 cases was reported to show tumors. Only in 1 out of 13 patients with residual metabolic changes a tumor relapse was detected. Overall 10-year survival in the groups of patients with and without FDG+ residual changes was 91 % and 100 %, respectively, with insignificant differences (p = 0.39).

Conclusion. PET-CT with 18F-FDG is a highly sensitive technique for evaluating the primary lesion volumes in PBL patients. In 100 % of bone and soft tissue lesions an intensive uptake of 18F-FDG was observed. At the same time our study showed persistent metabolic activity on completing antitumor treatment in more than a half of patients, and in most of them it was not caused by tumor. Therefore, in our view, ongoing residual metabolic activity in PBL cannot always be regarded as an indication for continued treatment or consolidation radiotherapy.

Keywords: primary bone lymphoma, survival, positron emission tomography, diagnosis, efficacy estimation of antitumor treatment.

Received: August 2, 2019

Accepted: December 5, 2019

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REFERENCES

  1. Matikas A, Briasoulis A, Tzannou I, et al. Primary bone lymphoma: a retrospective analysis of 22 patients treated in a single tertiary center. Acta Haematol. 2013;130(4):291–6. doi: 10.1159/000351051.

  2. Bacci G, Jaffe N, Emiliani E, et al. Therapy for primary non-Hodgkin’s lymphoma of bone and a comparison of results with Ewing’s sarcoma. Ten year’s experience at the Istituto Ortopedico Rizzoli. Cancer. 1986;57(8):1468–72. doi: 10.1002/1097-0142(19860415)57:8<1468::aid-cncr2820570806>3.0.co;2-0.

  3. Fidias P, Spiro I, Scobczak ML, et al. Long-term results of combined modality therapy in primary bone lymphomas. Int J Radiat Oncol Biol Phys. 1999;45(5):1213–38. doi: 10.1016/s0360-3016(99)00305-3.

  4. Messina C, Ferreri AJ, Govi S, et al. Clinical features, management and prognosis of multifocal primary bone lymphoma: a retrospective study of the international Extranodal Lymphoma Study Group (the IELSG 14 study). Br J Haematol. 2014;164(6):834–40. doi: 10.1111/bjh.12714.

  5. Морозова А.К., Звонков Е.Е., Мамонов В.Е. и др. Первичные лимфатические опухоли костей и мягких тканей: сравнительная оценка результатов лечения. Терапевтический архив. 2012;84(7):42–9.

    [Morozova AK, Zvonkov EE, Mamonov VE, et al. Primary lymphomas of bones and soft tissues: comparative assessment of treatment results. Terapevticheskii arkhiv. 2012;84(7):42–9. (In Russ)]

  6. Gabeeva NG, Zvonkov EE, Morozova AK, et al. Long-term follow-up of primary bone diffuse large B-cell lymphoma treated with m NHL-BFM-90. Blood. 2016;128(22):3025.

  7. Смольянинова А.К., Габеева Н.Г., Мамонов В.Е. и др. Первичная лимфома костей: 10-летние результаты проспективного исследования в одной клинике. Гематология и трансфузиология. 2018;63(S1):181.

    [Smol’yaninova AK, Gabeeva NG, Mamonov VE, et al. Primary bone lymphoma: 10-year results of a prospective single-center trial. Gematologiya i transfuziologiya. 2018;63(S1):181. (In Russ)]

  8. Lewis VO, Primus G, Anastasi J, et al. Oncologic outcomes of primary lymphomas of bone in adults. Clin Orthop Rel Res. 2003;415:90–7. doi: 10.1097/01.blo.0000093901.12372.ad.

  9. Ostrowski ML, Unni KK, Banks PM, et al. Malignant Lymphoma of Bone. Cancer. 1986;58(12):2646–55. doi: 10.1002/1097-0142(19861215)58:12<2646::aid-cncr2820581217>3.0.co;2-u.

  10. Смольянинова А.К., Габеева Н.Г., Мамонов В.Е. и др. Первичные лимфомы костей: долгосрочные результаты проспективного одноцентрового исследования. Клиническая онкогематология. 2019;12(3):247–62. doi: 10.21320/2500-2139-2019-12-3-247-262.

    [Smol’yaninova AK, Gabeeva NG, Mamonov VE, et al. Primary Bone Lymphomas: Long-Term Results of a Prospective Single-Center Trial. Clinical oncohematology. 2019;12(3):247–62. doi: 10.21320/2500-2139-2019-12-3-247-262. (In Russ)]

  11. Ueda T, Aozasa K, Ohsawa M, et al. Malignant lymphomas of bone in Japan. Cancer. 1989;64(11):2387–92. doi: 10.1002/1097-0142(19891201)64:11<2387::aid-cncr2820641132>3.0.co;2-1

  12. Meignan M, Barrington S, Itti E, et al. Report on the 4th international workshop on positron emission tomography in lymphoma held in Menton, France, 3–5 October 2012. Leuk Lymphoma. 2013;55(1):31–7. doi: 10.3109/10428194.2013.802784.

  13. Егорова Е.К., Габеева Н.Г., Мамонов В.Е. и др. Первичные лимфатические опухоли костей: описание двух случаев и обзор литературы. Онкогематология. 2008;3(4):5–10.

    [Egorova EK, Gabeeva NG, Mamonov VE, et al. Primary lymphatic tumors of bones: two case reports and a review of l Onkogematologiya. 2008;3(4):5–10. (In Russ)]

  14. Christie DR, Dear K, Le T, et al. Limited chemotherapy and shrinking field radiotherapy for osteolymphoma (primary bone lymphoma): results from the trans-Tasman Radiation Oncology Group 99.04 and Australasian Leukaemia and Lymphoma Group LY02 prospective trial. Int J Radiat Oncol Biol Phys. 2011;80(4):1164–70. doi: 10.1016/j.ijrobp.2010.03.036.

  15. Iwaya Y, Tekenaka K, Akamatsu T. Primary Gastric Diffuse Large B-cell Lymphoma with Orbital Involvement: Diagnostic Usefulness of 18-fluorodeoxyglucose Positron Emission Tomography. Intern Med. 2011;50(18):1953–6. doi: 10.2169/internalmedicine.50.5524.

  16. Demircay E, Hornicek J, Mankin HJ, at al. Malignant Lymphoma of Bone: A Review of 119 Patients. Clin Orthop Relat Res. 2013;471(8):2684–90. doi: 10.1007/s11999-013-2991-x.

  17. Fletcher CDM, Unni KK, Mertens F. (eds) Pathology and genetics of tumours of soft tissue and bone. World Health Organization Classification of Tumours. 3rd Edition. Lyon: IARC Press; 2002.

  18. Fletcher CDM. The evolving classification of soft tissue tumours: an update based on the new WHO classification. Histopathology. 2006;48(1):3–12. doi: 10.1111/j.1365-2559.2005.02284.x.

  19. Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F. World health organization classification of tumours of soft tissue and bone. 4th edition. Lyon: IARC Press; 2013. 468 p.

  20. Krishnan А, Shirkhoda А, Tehranzadeh Т, et al. Primary Bone Lymphoma: Radiographic–MR Imaging Correlation. RadioGraph. 2003;23(6):1371–87. doi: 10.1148/rg.236025056.

  21. Mulligani ME, Kransdorf MJ. Sequestra in Primary Lymphoma of Bone: Prevalence and Radiologic Features. Am J Roentgenol. 1993;160(6):1245–8. doi: 10.2214/ajr.160.6.8498226.

  22. Canete AN, Bloem HL, Kroon HM. Primary bone tumors of the spine. Radiologia. 2016;58(Suppl 1):68–80. doi: 10.1016/j.rx.2016.01.001.

  23. Mikhaeel NG. Primary bone lymphoma. Clin Oncol. 2012;24(5):366–70. doi: 10.1016/j.clon.2012.02.006.

  24. Hicks DC, Gokan T, O’Keefe RJ, et al. Primary lymphoma of bone: correlation of magnetic resonance imaging features with cytokine production by tumor cells. Cancer. 1995;75(4):973–80. doi: 10.1002/1097-0142(19950215)75:4<973::aid-cncr2820750412>3.0.co;2-8.

  25. Messina C, Christie D, Zucca E, et al. Primary and secondary bone lymphomas. Cancer Treat Rev. 2015;41(3):235–46. doi: 10.1016/j.ctrv.2015.02.001.

  26. Remier RR, Bruce AC, Yong RC, et al. Lymphoma Presenting in Bone. Results of Histopathology, Staging, and Therapy. Ann Inter Med. 1977;87(1):50–5. doi: 10.7326/0003-4819-87-1-50.

  27. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–67. doi: 10.1200/JCO.2013.54.8800.

  28. Jawad MU, Schneiderbauer MM, Min ES, et al. Primary Lymphoma of Bone in Adult Patients. Cancer. 2010;116(4):871–9. doi: 10.1002/cncr.24828.

  29. Schaefer NG, Strobel K, Taverna C, et al. Bone involvement in patients with lymphoma: the role of FDG-PET/CT. Eur J Nucl Med Mol Imag. 2007;34(1):60–7. doi: 10.1007/s00259-006-0238-8.

  30. Ramadan KM, Shenkier T, Sehn LH, et al. 131 patients with primary bone lymphoma: a population-based study of successively treated cohorts from the British Columbia Cancer Agency. Ann Oncol. 2007;18(1):129–35. doi: 10.1093/annonc/mdl329.

  31. Park YH, Kim S, Choi SJ, et al. Clinical impact of whole-body FDG-PET for evaluation of response and therapeutic decision-making of primary lymphoma of bone. Ann Oncol. 2005;16(8):1401–2. doi: 10.1093/annonc/mdi234.

  32. Park YH, Choi SJ, Ryoo BY, et al. PET imaging with F-18 fluorodeoxyglucose for primary lymphoma of bone. Clin Nucl Med. 2005;30(2):131–4. doi: 10.1097/00003072-200502000-00020.

  33. Singh Т, Satheesh С, Lakshmaiah С, et al. Primary bone lymphoma: A report of two cases and review of the literature. J Cancer Res Ther. 2010;6(3):296–8. doi: 10.4103/0973-1482.73366.

  34. Wang LJ, Wu HB, Wang M, et al. Utility of F-18 FDG PET/CT on the evaluation of primary bone lymphoma. Eur J Radiol. 2015;84(11):2275–9. doi: 10.1016/j.ejrad.2015.09.011.

  35. Baar J, Burkes RL, Gospodarowicz M. Primary non-Hodgkin’s lymphoma of bone. Semin Oncol. 1999;26(3):270–5.

  36. Liu Y. The role of 18F-FDG PET/CT in staging and restaging primary bone lymphoma. Nucl Med Commun. 2017;38(4):319–24. doi: 10.1097/MNM.0000000000000652.

  37. Kim SY, Shin DY, Lee SS. Clinical characteristics and outcomes of primary bone lymphoma in Korea. Korean J Hematol. 2012;47(3):213–8. doi: 10.5045/kjh.2012.47.3.213.

  38. Milks KS, McLean TW, Anthony EY. Imaging of primary pediatric lymphoma of bone. Pediatr Radiol. 2016;46(8):1150–7. doi: 10.1007/s00247-016-3597-8.

  39. Zinzani PL, Carrillo G, Ascani S, et al. Primary bone lymphoma: experience with 52 patients. Haematologica. 2003;88(3):280–5.

  40. Baar J, Burkes R, Bell R. Primary Non-Hodgkin’s Lymphoma of Bone. A clinicopathologic study. Cancer. 1994;73(4):1194–9. doi: 10.1002/1097-0142(19940215)73:4<1194::aid-cncr2820730412>3.0.co;2-r.

  41. Choi J, Raghavan M. Diagnostic imaging and Image-Guided Therapy of Skeletal Metastases. Cancer Control. 2012;19(2):102–12. doi: 10.1177/107327481201900204.

  42. Hwang S. Imaging of lymphoma of musculoskeletal system. Magn Reson Imag Clin N Am. 2010;18(1):75–93. doi: 10.1016/j.mric.2009.09.006.

  43. Rapoport AP, Constine LS, Packman CH, et al. Treatment of Multifocal Lymphoma of Bone With Intensified Promace-Cytabom Chemotherapy and Involved Field Radiotherapy. Am J Hematol. 1998;58(1):1–7. doi: 10.1002/(SICI)1096-8652(199805)58:1<1::AID-AJH1>3.0.CO;2-X.

  44. Seymour JF. Extra-nodal lymphoma in rare localisations: bone, breast and testes. Hematol Oncol. 2013;31(Suppl 1):60–3. doi: 10.1002/hon.2081.

  45. Ng AP, Wirth A, Seymour JF, et al. Early therapeutic response assessment by (18)FDG-positron emission tomography during chemotherapy in patients with diffuse large B-cell lymphoma: Isolated residual positivity involving bone is not usually a predictor of subsequent treatment failure. Leuk Lymphoma. 2007;48(3):596–600. doi: 10.1080/10428190601099965.

  46. Rigacci L, Kovalchuk S, Berti V, et al. The use of Deauville 5-point score could reduce the risk of false-positive fluorodeoxyglucose-positron emission tomography in the posttherapy evaluation of patients with primary bone lymphomas. World J Nucl Med. 2018;17(3):157–65. doi: 10.4103/wjnm.WJNM_42_17.

  47. Juweid ME, Wiseman GA, Vose JM, et al. Response assessment of aggressive non-Hodgkin’s lymphoma by integrated International Workshop Criteria and fluorine-18-fluorodeoxyglucose positron emission tomography. J Clin Oncol. 2005;23(21):4652–61. doi: 10.1200/JCO.2005.01.891.

  48. Cheson BD, Pfistner B, Juweid ME, et al. International Harmonization Project for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86. doi: 10.1200/JCO.2006.09.2403.

  49. Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007;25(5):571–8. doi: 10.1200/JCO.2006.08.2305.

  50. Albano D, Agnello F, Patti C, et al. Whole-body magnetic resonance imaging and FDG-PET/CT for lymphoma staging: Assessment of patient experience. Egypt J Radiol Nucl Med. 2017;48(4):1043–7. doi: 1016/j.ejrnm.2017.06.002.

  51. Wang D, Huo Y, Chen S et al. Whole-body MRI versus 18F-FDG PET/CT for pretherapeutic assessment and staging of lymphoma: a meta-analysis. OncoTarg Ther. 2018;11:3597–608. doi: 10.2147/OTT.S148189.

  52. Galia M, Albano D, Tarella C, et al. Whole body magnetic resonance in indolent lymphomas under watchful waiting: the time is now. Eur Radiol. 2017;28(3):1187–93. doi: 10.1007/s00330-017-5071-x.

  53. Toledano-Massiah S, Luciani A, Itti E, et al. Whole-Body Diffusion-weighted Imaging in Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma. RadioGraph. 2015;35(3):747–64. doi: 10.1148/rg.2015140145.

  54. Koh D, Collins DJ. Diffusion-Weighted MRI in the Body: Applications and Challenges in Oncology. Am J Roentgenol. 2007;188(6):1622–35. doi: 10.2214/AJR.06.1403.

Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues

LYMPHOID TUMORS , , , , , ,

KD Kaplanov1,2, NP Volkov1, TYu Klitochenko1, IV Matveeva1, AL Shipaeva1, MN Shirokova1, NV Davydova3, EG Gemdzhian4, DS Abramov5, DM Konovalov5, GL Snigur2, NA Red’kina1

1 Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

2 Volgograd Medical Scientific Center, 1G Rokossovskogo str., Volgograd, Russian Federation, 400081

3 Consultation and Diagnosis Polyclinic No. 2, 114A Angarskaya str., Volgograd, Russian Federation, 400081

4 National Medical Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

5 Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117997

For correspondence: Kamil’ Daniyalovich Kaplanov, MD, PhD, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; e-mail: kamilos@mail.ru

For citation: Kaplanov KD, Volkov NP, Klitochenko TYu, et al. Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues. Clinical oncohematology. 2019;12(2):154–64.

DOI: 10.21320/2500-2139-2019-12-2-154-164

ABSTRACT

Background & Aims. At least one third of patients with diffuse large B-cell lymphoma (DLBCL) are resistant to first-line therapy. R-CHOP chemo-immunotherapy does not yield acceptable results in high-risk patients. Effectiveness of options based either on increasing the dose intensity or on including auto-HSCT into the first-line therapy was not supported by the results of controlled studies. With this background the present study focuses on options, issues and failures of first-line on the basis of long-term follow-up of DLBCL patient population in the Volgograd Region.

Materials & Methods. From 2004 to 2017 the population-based registry of the Hematology Department in the Volgograd Regional Clinical Oncology Dispensary included all 492 primary DLBCL patients: 235 (48 %) men and 257 (52 %) women aged 18 to 88 years. Mean and median age was 59 and 61 years, respectively. CHOP therapy was administered to 206 (42 %) patients, and 223 (45 %) patients received R-CHOP. Other regimens including NHL-BFM-90 and R-DA-EPOCH were used only in 63 (13 %) patients. Second- and third-line therapies were administered to 145 (30 %) and 54 (11 %) patients, respectively. Value of the International Prognostic Index (IPI) and immunomorphologic characteristics was determined by multivariate Cox regression analysis. Pharmacoeconomic aspect of first-line therapy failures was analyzed using Markov model.

Results. Improvement of DLBCL therapy effects with the use of R-CHOP chemo-immunotherapy is particularly obvious in the groups with favorable and intermediate prognosis with 5-year overall survival (OS) of 90 % and 69 %, respectively. R-CHOP results are not considered to be satisfactory in the high-risk group: 5-year OS was 38 %. Pharmacoeconomic analysis proves the advantage of chemo-immunotherapy strategy in comparison with the period before rituximab era in terms of the life years gained (LYG) and the incremental cost-effectiveness ratio (ICER). With respect to immunotherapy effects the most significant immunomorphologic parameter is bcl-2 tumor cell expression. In the group of patients with bcl-2 > 50 % 5-year OS was 61 % with median of 88 months, event-free survival (EFS) was 52 % with median of 62 months. In the group without bcl-2 expression above the threshold 5-year OS and EFS were 88 % and 75 %, respectively, medians were not achieved. With c-myc and bcl-2 coexpression EFS and OS appeared to be even worse: 5-year EFS was 29 % with median of 6 months, and 5-year OS was 31 % with median of 15 months.

Conclusion. The analysis of actual practice demonstrates the need for new options of first-line therapy for DLBCL high-risk patients and also for introducing new discriminating prognostic factors which include the IPI-independent ones.

Keywords: diffuse large B-cell lymphoma, R-CHOP, chemoimmunotherapy, survival, pharmacoeconomics, Markov model, life years gained (LYG), incremental cost-effectiveness ratio (ICER).

Received: July 16, 2018

Accepted: January 10, 2019

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REFERENCES

  1. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol. 1998;16(8):2780–95. doi: 10.1200/JCO.1998.16.8.2780.

  2. Smith A, Howell D, Patmore R, et al. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer. 2011;105(11):1684–92. doi: 10.1038/bjc.2011.450.

  3. Cunningham D, Hawkes EA, Jack A, et al. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013;381(9880):1817–26. doi: 10.1016/S0140-6736(13)60313-X.

  4. Ziepert, M, Hasenclever D, Kuhnt E, et al. Standard international prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(14):2373–80. doi: 10.1200/JCO.2009.26.2493.

  5. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90. doi: 10.1182/blood-2016-01-643569.

  6. Sehn LH, Gascoyne RD. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 2015;125(1):22–32. doi: 10.1182/blood-2014-05-577189.

  7. Tilly H, Gomes da Silva M, Vitolo U, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v116–25. doi: 10.1093/annonc/mdv304.

  8. Prochazka KT, Melchardt T, Posch F, et al. NCCN-IPI score-independent prognostic potential of pretreatment uric acid levels for clinical outcome of diffuse large B-cell lymphoma patients. Br J Cancer. 2016;115(10):1264–72. doi: 10.1038/bjc.2016.325.

  9. Montalban C, Diaz-Lopez A, Dlouhy I, et al. Validation of the NCCN-IPI for diffuse large B-cell lymphoma (DLBCL): the addition of beta2-microglobulin yields a more accurate GELTAMO-IPI. Br J Haematol. 2017;176(6):918–28. doi: 10.1111/bjh.14489.

  10. Wight J, Chong G, Grigg A, et al. Prognostication of diffuse large B-cell lymphoma in the molecular era: moving beyond the IPI. Blood. 2018;32(5):400–15. doi: 10.1016/j.blre.2018.03.005.

  11. Khor S, Beca J, Krahm M, et al. Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: A population-based analysis. BMC Cancer. 2014;14(1):586. doi: 10.1186/1471-2407-14-586.

  12. Van Keep M, Gairy K, Seshagiri D, et al. Cost-effectiveness analysis of bortezomib in combination with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (VR-CAP) in patients with previously untreated mantle cell lymphoma. BMC Cancer. 2016;16(1):598. doi: 10.1186/s12885-016-2633-2.

  13. Капланов К.Д., Шипаева А.Л., Васильева В.А. и др. Международный прогностический индекс при распространенных стадиях лимфомы Ходжкина в условиях современной терапии. Клиническая онкогематология. 2013;6(3):294–302.

    [Kaplanov KD, Shipaeva AL, Vasil’eva VA, et al. International prognostic score in advanced Hodgkin’s lymphoma. Klinicheskaya onkogematologiya. 2013;6(3):294–302. (In Russ)]

  14. Капланов К.Д., Шипаева А.Л., Васильева В.А. и др. Эффективность программ химиотерапии первой линии при различных стадиях лимфомы Ходжкина. Клиническая онкогематология. 2012;5(1):22–9.

    [Kaplanov KD, Shipaeva AL, Vasil’eva VA, et al. Efficacy of first line chemotherapy programs for different stages of Hodgkin’s lymphomas. Klinicheskaya onkogematologiya. 2012;5(1):22–9. (In Russ)]

  15. Капланов К.Д., Волков Н.П., Клиточенко Т.Ю. и др. Первая линия терапии лимфомы из клеток зоны мантии: анализ эффективности и клинико-экономическая оценка. Клиническая онкогематология. 2018;11(2):150–9. doi: 10.21320/2500-2139-2018-11-2-150-159.

    [Kaplanov KD, Volkov NP, Klitochenko TYu, et al. First-Line Treatment of Mantle-Cell Lymphoma: Analysis of Effectiveness and Cost-Effectiveness. Clinical oncohematology. 2018;11(2):150–9. doi: 10.21320/2500-2139-2018-11-2-150-159. (In Russ)]

  16. Abner EL, Charnigo RJ, Kryscio RJ, et al. Markov chains and semi-Markov models in time-to-event analysis. J Biom Biostat. 2013;S1:e001. doi: 10.4172/2155-6180.S1-e001.

  17. Wyndham W, Jung sin-Ho, Brandelyn P, et al. Phase III Randomized Study of R-CHOP Versus DA-EPOCH-R and Molecular Analysis of Untreated Diffuse Large B-Cell Lymphoma: CALGB/Alliance 50303. Blood. 2016;128:469.

  18. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329(14):987–94. doi: 10.1056/NEJM199309303291402.

  19. Wang HI, Smith A, Aas E, et al. Treatment cost and life expectancy of diffuse large B-cell lymphoma (DLBCL): a discrete event simulation model on a UK population-based observational cohort. Eur J Health Econ. 2017;18(2):255–67. doi: 10.1007/s10198-016-0775-4.

  20. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010; 28(27):4184–90. doi: 10.1200/JCO.2010.28.1618.

  21. Gisselbrecht C, Schmitz N, Mounier N, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012;30(36):4462–9. doi: 10.1200/JCO.2012.41.9416.

  22. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800–8. doi: 10.1182/blood-2017-11-817775.

  23. Sehn LH, Berry B, Chhanabhai M, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007;109(5):1857–61. doi: 10.1182/blood-2006-08-038257.

  24. Gang AO, Pedersen M, d’Amore F, et al. A clinically based prognostic index for diffuse large B-cell lymphoma with a cut-off at 70 years of age significantly improves prognostic stratification: population-based analysis from the Danish Lymphoma Registry. Leuk Lymphoma. 2015;56(9):2556–62. doi: 10.3109/10428194.2015.1010078.

  25. Zhou Z, Sehn LH, Rademaker AW, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood 2014;123(6):837–42. doi: 10.1182/blood-2014-06-583476.

  26. Royston P, Altman DG, Sauerbrei W. Dichotomizing continuous predictors in multiple regression: a bad idea. Stat Med. 2006;25(1):127–41. doi: 10.1002/sim.2331.

  27. Harrell FE. Regression modeling strategies. New York: Springer-Verlag; 2001. doi: 10.1007/978-1-4757-3462-1.

  28. Biccler J, Eloranta S, de Nully Brown P, et al. Simplicity at the cost of predictive accuracy in diffuse large B-cell lymphoma: a critical assessment of the R-IPI, IPI, and NCCN-IPI. Cancer Med. 2018;7(1):114–22. doi: 10.1002/cam4.1271.

  29. Johnson NA, Slack GW, Savage KJ, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30(28):3452–9. doi: 10.1200/JCO.2011.41.0985.

  30. Schneider KMС, Banks PM, Collie AM, et al. Dual expression of MYC and BCL2 proteins predicts worse outcomes in diffuse large B-cell lymphoma. Leuk Lymphoma. 2016;57(7):1640–8. doi: 10.3109/10428194.2015.1101099.

  31. Barrans SL, Evans PA, O’Connor SJ, et al. The t(14;18) is associated with germinal center-derived diffuse large B-cell lymphoma and is a strong predictor of outcome. Clin Cancer Res. 2003;9(6):2133–9.

  32. Tsuyama N, Sakata S, Baba S, et al. BCL2 expression in DLBCL: reappraisal of immunohistochemistry with new criteria for therapeutic biomarker evaluation. Blood. 2017;130(4):489–500. doi: 10.1182/blood-2016-12-759621.

  33. Burton C, Barrans S, Ahmed S, et al. Cross-Platform validation of gene expression profiling (GEP) based cell of origin classification in a clinical laboratory setting. Hematol Oncol. 2017;35(S2):107. doi: 10.1002/hon.2437_96.

Clinical Efficacy of Chelation Therapy in Patients with Low-Risk Myelodysplastic Syndrome

REVIEWS , , , ,

SV Gritsaev, II Kostroma, AA Zhernyakova

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Sergei Vasil’evich Gritsaev, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-54-68; e-mail: gritsaevsv@mail.ru

For citation: Gritsaev SV, Kostroma II, Zhernyakova AA. Clinical Efficacy of Chelation Therapy in Patients with Low-Risk Myelodysplastic Syndrome. Clinical oncohematology. 2019;12(2):120–4.

DOI: 10.21320/2500-2139-2019-12-2-120-124

ABSTRACT

The present literature review provides evidence that in patients with low-risk myelodysplastic syndrome and transfusion dependence blood parameters and survival rates can be improved by administration of iron chelators. Dose adequacy and therapy duration underlie clinical efficacy of chelators. Toxicity can be reduced by administrating a new formula of deferasirox that does not need to be dissolved in liquid before consuming.

Keywords: myelodysplastic syndrome, low risk, transfusion dependence, iron chelators, survival.

Received: August 20, 2018

Accepted: February 2, 2019

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REFERENCES

  1. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88.

  2. Bennett JM. Consensus statement on iron overload in myelodysplastic syndromes. Am J Hematol. 2008;83(11):858–61. doi: 10.1002/ajh.21269.

  3. Malcovati L, Porta MG, Pascutto C, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005;23(30):7594–603. doi: 1200/JCO.2005.01.7038.

  4. Steensma DP, Bennett JM. The myelodysplastic syndromes: Diagnosis and treatment. Mayo Clin Proc. 2006;81(1):104–30. doi: 10.4065/81.1.104.

  5. Mitchell M, Gore SD, Zeidan AM. Iron chelation therapy in myelodysplastic syndromes: where do we stand? Expert Rev Hematol. 2013;6(4):397–410. doi: 10.1586/17474086.2013.814456.

  6. Gattermann N, Jarisch A, Schlag R, et al. Deferasirox treatment of iron-overloaded chelation-naive and prechelated patients with myelodysplastic syndromes in medical practice: results from the observational studies eXtend and eXjange. Eur J Haematol. 2012;88(3):260–8. doi: 10.1111/j.1600-0609.2011.01726.x.

  7. List AF, Baer MR, Steensma DP, et al. Deferasirox reduces serum ferritin and labile plasma iron in RBC transfusion-dependent patients with myelodysplastic syndrome. J Clin Oncol. 2012;30(17):2134–9. doi: 10.1200/JCO.2010.34.1222.

  8. Greenberg PL, Koller CA, Cabantchik ZI, et al. Prospective assessment of effects on iron-overload parameters of deferasirox therapy in patients with myelodysplastic syndromes. Leuk Res. 2010;34(12):1560–5. doi: 10.1016/j.leukres.2010.06.013.

  9. Remacha AF, Arrizabalaga B, Del Canizo C, et al. Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements. Ann Hematol. 2010;89(2):147–54. doi: 10.1007/s00277-009-0794-7.

  10. Rose C, Brechignac S, Vassilief D, et al. Does iron chelation therapy improve survival in regularly transfused lower risk MDS patients? A multicenter study by the GFM (Groupe Francophone des Myelodysplasies). Leuk Res. 2010;34(7):864–70. doi: 10.1016/j.leukres.2009.12.004.

  11. Malcovati L. Impact of transfusion dependency and secondary iron overload on the survival of patients with myelodysplastic syndromes. Leuk Res. 2007;31(Suppl 3):S2–6. doi: 10.1016/S0145-2126(07)70459-9.

  12. Kohgo Y, Ikuta K, Ohtake T, et al. Body iron metabolism and pathophysiology of iron overload. Int J Hematol. 2008;88(1):7–15. doi: 10.1007/s12185-008-0120-5.

  13. Andrews NC. Closing the iron gate. N Engl J Med. 2012;366(4):376–7. doi: 10.1056/NEJMcibr1112780.

  14. Gardenghi S, Marongiu MF, Ramos P, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. 2007;109(11):5027–35. doi: 10.1182/blood-2006-09-048868.

  15. Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999;341(26):1986–95. doi: 10.1056/NEJM199912233412607.

  16. Takatoku M, Uchiyama T, Okamoto S, et al. Retrospective nationwide survey of Japanese patients with transfusion-dependent MDS and aplastic anemia highlights the negative impact of iron overload on morbidity/mortality. Eur J Haematol. 2007;78(6):487–94. doi: 10.1111/j.1600-0609.2007.00842.x.

  17. Gattermann N. Iron overload in myelodysplastic syndromes. Int J Hematol. 2018;107(1):55–63. doi: 10.1007/s12185-017-2367-1.

  18. Lyons R, Marek B, Paleyc C, et al. Relation between chelation and clinical outcomes in lower-risk patients with myelodysplastic syndromes: Registry analysis at 5 years. Leuk Res. 2017;56:88–95. doi: 10.1016/j.leukres.2017.01.033.

  19. Leitch H, Parmar A, Wells R, et al. Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient-related factors and measuring from time of first red blood cell transfusion dependence: an MDS-CAN analysis. Br J Haematol. 2017;179(1):83–97. doi: 10.1111/bjh.14825.

  20. Mainous A, Tanner R, Hulihan M, et al. The impact of chelation therapy on survival in transfusional iron overload: a meta-analysis of myelodysplastic syndrome. Br J Haematol. 2014;167(5):720–3. doi: 10.1111/bjh.13053.

  21. Abraham I, Yami M, Yun S et al. Survival outcomes in iron chelated and non-chelated patients with lower-risk myelodysplastic syndromes: Review and pooled analysis of observational studies. Leuk Res. 2017;57:104–8. doi: 10.1016/j.leukres.2017.03.007.

  22. Gattermann N, Finelli C, Della Porta M, et al. Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes. Haematologica. 2012;97(9):1364–71. doi: 10.3324/haematol.2011.048546.

  23. Pullarkat V. Objectives of iron chelation therapy in myelodysplastic syndromes: more than meets the eye? Blood. 2009;114(26):5251–5. doi: 10.1182/blood-2009-07-234062.

  24. Zeidan AM, Hendrick F, Friedmann E, et al. Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes. J Comp Eff Res. 2015;4(4):327–40. doi: 10.2217/cer.15.20.

  25. Improta S, Villa MR, Volpe A, et al. Transfusion-dependent low-risk myelodysplastic patients receiving deferasirox: Long-term follow-up. Oncol Lett. 2013;6(6):1774–8. doi: 10.3892/ol.2013.1617.

  26. Breccia M, Voso M, Spiriti M, et al. An increase in hemoglobin, platelets and white blood cells levels by iron chelation as single treatment in multitransfused patients with myelodysplastic syndromes: clinical evidences and possible biological mechanisms. Ann Hematol. 2015;94(5):771–7. doi: 10.1007/s00277-015-2341-z.

  27. Delforge M, Selleslag D, Beguin Y, et al. Adequate iron chelation therapy for at least six months improves survival in transfusion-dependent patients with lower risk myelodysplastic syndromes. Leuk Res. 2014;38(5):557–63. doi: 10.1016/j.leukres.2014.02.003.

  28. Cermak J, Jonasova A, Vondrakova J, et al. A comparative study of deferasirox and deferiprone in the treatment of iron overload in patients with myelodysplastic syndromes. Leuk Res. 2013;37(12):1612–5. doi: 10.1016/j.leukres.2013.07.021.

  29. Nolte F, Angelucci E, Breccia M, et al. Updated recommendations on the management of gastrointestinal disturbances during iron chelation therapy with deferasirox in transfusion dependent patients with myelodysplastic syndrome – emphasis on optimized dosing schedules and new formulations. Leuk Res. 2015;39(10):1028–33. doi: 10.1016/j.leukres.2015.06.008.

  30. Taher AT, Origa R, Perrotta S, et al. New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study. Am J Hematol. 2017;92(5):420–8. doi: 10.1002/ajh.24668.

  31. Джадену® (инструкция по медицинскому применению). Швейцария: Novartis pharma, AG. Доступно по: https://www.vidal.ru/drugs/dzhadenu. Ссылка активна на 30.11.2018. [Dzhadenu® (package insert). Switzerland: Novartis pharma, AG. Available from: https://www.vidal.ru/drugs/dzhadenu. (accessed 30.11.2018) (In Russ)]

Epidemiology of Multiple Myeloma in Novosibirsk (Siberian Federal District)

LYMPHOID TUMORS , , , , ,

NV Skvortsova1, TI Pospelova1, IB Kovynev1, GS Soldatova2, IN Nechunaeva3

1 Novosibirsk State Medical University, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091

2 Novosibirsk National Research State University, 2 Pirogova str., Novosibirsk, Russian Federation, 630090

3 Municipal Clinical Hospital No. 2 of Novosibirsk Region, Center of Hematology, 21 Polzunov str., Novosibirsk, Russian Federation, 630051

For correspondence: Nataliya Valer’evna Skvortsova, MD, PhD, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091; Tel.: +7(905)955-59-91; e-mail: nata_sk78@mail.ru.

For citation: Skvortsova NV, Pospelova TI, Kovynev IB, et al. Epidemiology of Multiple Myeloma in Novosibirsk (Siberian Federal District). Clinical oncohematology. 2019;12(1):86–94.

DOI: 10.21320/2500-2139-2019-12-1-86-94

ABSTRACT

Aim. To analyze major epidemiological parameters of multiple myeloma, i.e. registered incidence, prevalence, mortality, and survival in Novosibirsk, megalopolis in Siberian Federal District.

Materials & Methods. The study covered medical records of 335 patients with newly diagnosed multiple myeloma (MM) treated from January 1, 2006 to December 31, 2016 at the Center of Hematology in Novosibirsk. Median age was 67 years (range 30–89), the trial enrolled 218 (65 %) women and 117 (35 %) men.

Results. Over the last decade the mean registered MM incidence in Novosibirsk increased by 1.6 times, and MM prevalence increased by 4.9 times. These parameters correspond to 2.4 and 13.8 per 100,000 population per year, respectively, with the linear trend of growth which demonstrates not only the increased number of patients with newly diagnosed MM, but the increased longevity of them. MM incidence and prevalence parameters are significantly higher in women than in men, which most probably can be accounted for by specific administrative factors in the Novosibirsk region. Yearly mortality of MM patients decreased from 28.3 % to 8.2 % with a negative linear trend over the entire analyzed period, which is most likely to be associated with availability of new drugs and transplantation procedures.

Conclusion. The obtained epidemiological data will enable to plan the provision of timely and effective care for MM patients and to elaborate a system of judicious allocation of costly equipment and drugs.

Keywords: multiple myeloma, epidemiology, registered incidence, prevalence, mortality, survival.

Received: September 24, 2018

Accepted: December 27, 2018

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REFERENCES

  1. Менделеева Л.П., Вотякова О.М., Покровская О.С. и др. Национальные клинические рекомендации по диагностике и лечению множественной миеломы. Гематология и трансфузиология. 2016;61(1, прил. 2):1–24. doi: 10.18821/0234-5730-2016-61-1(Прил.2).

    [Mendeleeva LP, Votyakova OM, Pokrovskaya OS, et al. National clinical guidelines on diagnosis and treatment of multiple myeloma. Gematologiya i transfuziologiya. 2016;61(1, Suppl 2):1–24. doi: 10.18821/0234-5730-2016-61-1(Прил.2). (In Russ)]

  2. Kyle RA, Rajkumar SV. Epidemiology of the plasma-cell disorders. Best Pract Res Clin Haematol. 2007;20(4):637–64. doi: 10.1016/j.beha.2007.08.001.

  3. Waxman AJ, Mink PJ, Devesa SS, et al. Racial disparities in incidence and outcome in multiple myeloma: a population-based study. Blood. 2010;116(25):5501–6. doi: 10.1182/blood-2010-07-298760.

  4. de Queiroz Crusoe E, Marinho da Silva AM, Agareno J, et al. Multiple myeloma: a rare case in an 8-year-old child. Clin Lymph Myel Leuk. 2015;15(1):e31–3. doi: 10.1016/j.clml.2014.08.004.

  5. Аль-Ради Л.С., Белоусова И.Э., Барях Е.А. и др. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Современная онкология. 2013;Экстравыпуск:6–102.

    [Al’-Radi LS, Belousova IE, Baryakh EA, et al. Russian clinical guidelines on diagnosis and treatment of lymphoproliferative disorders. Sovremennaya onkologiya. 2013;Special Issue:6–102. (In Russ)]

  6. Ковынев И.Б., Поспелова Т.И., Агеева Т.А. и др. Частота и структура неходжкинских злокачественных лимфом в Новосибирске, НСО и городах Сибирского федерального округа. Бюллетень Сибирского отделения РАМН. 2006;26(4):175–81.

    [Kovynev IB, Pospelova TI, Ageeva TA, et al. Incidence and structure of non-Hodgkin’s malignant lymphomas in Novosibirsk, Novosibirsk Region, and cities of Siberian Federal District. Byulleten’ Sibirskogo otdeleniya RAMN. 2006;26(4):175–81. (In Russ)]

  7. Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignance. Semin Oncol. 2016;43(6):676–81. doi: 10.1053/j.seminoncol.2016.11.004.

  8. Becker N. Epidemiology of multiple myeloma. Rec Res Cancer Res. 2011;183:25–35. doi: 10.1007/978-3-540-85772-3_2.

  9. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin. 2007;57(1):43–66. doi: 10.3322/canjclin.57.1.43.

  10. Ruzafa JC, Merinopoulou E, Baggaley RF, et al. Patient population with multiple myeloma and transitions across different lines of therapy in the USA: an epidemiologic model. Pharmacoepidemiol Drug Saf. 2016;25(8):871–9. doi: 10.1002/pds.3927.

  11. Rosenberg PS, Barker KA, Anderson WF. Future distribution of multiple myeloma in the United States by sex, age, and race/ethnicity. Blood. 2015;125(2):410–2. doi: 10.1182/blood-2014-10-609461.

  12. Yamabe K, Inoue S, Hiroshima C. Epidemiology and burden of multiple myeloma in Japan: a systematic review. Value Health. 2015;18(7):A449. doi: 10.1016/j.jval.2015.09.1129.

  13. Hong J, Lee JH. Recent advances in multiple myeloma: a Korean perspective. Korean J Intern Med. 2016;31(5):820–34. doi: 10.3904/kjim.2015.408.

  14. Chen XC, Chen XZ. Epidemiological differences in haematological malignancies between Europe and China. Lancet Oncol. 2014;15(11):е471–2. doi: 10.1016/S1470-2045(14)70441-3.

  15. Chen JH, Chung CH, Wang YC, et al. Prevalence and mortality-related factors of multiple myeloma in Taiwan. PLoS One. 2016;11(12):e0167227. doi: 10.1371/journal.pone.0167227.

  16. Лучинин А.С., Семочкин С.В., Минаев Н.В. и др. Эпидемиология множественной миеломы по данным анализа популяционного регистра Кировской области. Онкогематология. 2017;12(3):50–6. doi: 10.17650/1818-8346-2017-12-3-50-56.

    [Luchinin AS, Semochkin SV, Minaeva NV, et al. Epidemiology of Multiple Myeloma According to the Кirov Region Population Registers. Oncohematology. 2017;12(3):50–6. doi: 10.17650/1818-8346-2017-12-3-50-56. (In Russ)]

  17. Kristinsson SY, Landgren O, Dickman PW, et al. Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol. 2007;25(15):1993–9. doi: 10.1200/jco.2006.09.0100.

  18. Brenner H, Gondos A, Pulte D. Recent major improvements in long-term survival of younger patients with multiple myeloma. Blood. 2008;111(5):2521–6. doi: 10.1182/blood-2007-08-104984.

  19. Schaapveld M, Visser O, Siesling S, et al. Improved survival among younger but not among older patients with multiple myeloma in the Netherlands, a population-based study since 1989. Eur J Cancer. 2010;46(1):160–9. doi: 10.1016/j.ejca.2009.07.006.

  20. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111(5):2516–20. doi: 10.1182/blood-2007-10-116129.

  21. Altekruse SF, Kosary CL, Krapcho M, et al. SEER Cancer Statistics Review. Bethesda, MD: National Cancer Institute; 1975–2007. Available from: http://seer.cancer.gov/csr/1975_2007/ (accessed 6.11.2018).

  22. Каприн А.Д., Старинский В.В., Петрова Г.В. Злокачественные новообразования в России в 2015 г. (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена, 2017. 250 с.

    [Kaprin AD, Starinskii VV, Petrova GV. Zlokachestvennye novoobrazovaniya v Rossii v 2015 g. (zabolevaemost’ i smertnost’). (Malignant neoplasms in Russia in 2015: incidence and mortality.) Moscow: PA Herzen MNIOI Publ.; 2017. 250 p. (In Russ)]

  23. Володичева Е.М., Воробьева Т.В., Пивник А.В. Анализ заболеваемости множественной миеломой в Тульской области. Проблемы гематологии и переливания крови. 2000;4:31–4.

    [Volodicheva EM, Vorob’eva TV, Pivnik AV. Analysis of multiple myeloma incidence in the Tula region. Problemy gematologii i perelivaniya krovi. 2000;4:31–4. (In Russ)]

  24. Капорская Т.С., Киселев И.В., Силин А.П. Анализ заболеваемости множественной миеломой в Иркутской области. Сибирский медицинский журнал. 2006;66(8):65–7.

    [Kaporskaya TS, Kiselev IV, Silin AP. Analysis of multiple myeloma incidence in the Irkutsk region. Sibirskii meditsinskii zhurnal. 2006;66(8):65–7. (In Russ)]

  25. Гильфанова Л.Р., Крисанкова К.А. Новосибирская агломерация: проблемы и перспективы развития. Новая наука: теоретический и практический взгляд. 2017;1(4):116–9.

    [Gil’fanova LR, Krisankova KA. Novosibirsk agglomeration: challenges and prospects for the development. Novaya nauka: teoreticheskii i prakticheskii vzglyad. 2017;1(4):116–9. (In Russ)]

  26. Региональная база статистических данных «Новосибирская область» [электронный документ]. Доступно по: http://www.novosibstat.gks.ru. Ссылка активна на 6.11.2018.

    [Regional statistical database “Novosibirsk region” [Internet]. Available from: http://www.novosibstat.gks.ru. (accessed 6.11.2018) (In Russ)]

  27. Durie BGM, Harousseau J-L, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467–73. doi: 10.1038/sj.leu.2404284.

  28. Pulte D, Jansen L, Castro FA, et al. Trends in survival of multiple myeloma patients in Germany and the United States in the first decade of the 21st century. Br J Haematol. 2015;171(2):189–96. doi: 10.1111/bjh.13537.

  29. Лосева М.И., Поспелова Т.И., Гавалова Р.Ф. и др. Полиорганная патология у больных гемобластозами в отдаленном периоде лечения. Терапевтический архив. 1999;71(7):39–42.

    [Loseva MI, Pospelova TI, Gavalova RF, et al. Multiple organ failure in patients with tumors of hematopoietic tissue during long-term follow-up. Terapevticheskii arkhiv. 1999;71(7):39–42. (In Russ)]

Clinical and Hematological Predictors of Response to First-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma

LYMPHOID TUMORS , , ,

SV Samarina1, EL Nazarova1, NV Minaeva1, EN Zotina1, IV Paramonov1, SV Gritsaev2

1 Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

2 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Svetlana Valer’evna Samarina, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; e-mail: samarinasv2010@mail.ru

For citation: Samarina SV, Nazarova EL, Minaeva NV, et al. Clinical and Hematological Predictors of Response to First-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2019;12(1):68–72.

DOI: 10.21320/2500-2139-2019-12-1-68-72

ABSTRACT

Aim. To assess the prognostic value of clinical and hematological parameters used by hematologists for risk stratification in diffuse large B-cell lymphoma (DLBCL), and to justify the need for discovering new prognostic factors.

Methods. The trial included 101 patients (48 men and 53 women) with newly diagnosed DLBCL at the age of 18–80 years (median age 58 years). The patients received R-CHOP as first-line therapy. Depending on their response all patients were stratified into 4 groups: with complete response (CR; n = 58), partial response (PR; n = 15), resistance to first-line therapy (n = 19), and early relapses (ER; n = 9). Median follow-up was 22 months (range 2–120 months).

Results. In terms of age influence on the efficacy of R-СНОР as first-line therapy no significant differences were established in regard to response in patients younger and older than 65 years. Statistically significant differences were observed while analyzing two parameters of International Prognostic Index (IPI; disease stage and extranodal lesions) and B-symptoms in the CR and therapy-resistant groups. With respect to the same parameters no significant differences were found in the CR and ER groups. Median 2-year disease-free survival was not achieved in patients with CR. In patients with PR it was 12 months. Median 2-year overall survival in patients with CR, PR, and ER was not achieved, and in patients with therapy-resistant DLBCL it was 10 months.

Conclusion. Results of the trial confirm prognostic value of factors applied for risk stratification in DLBCL. However, variability of clinical course of the disease, especially with a low IPI score, suggests the need for new prognostic parameters associated with the course of DLBCL.

Keywords: diffuse large B-cell lymphoma, prognosis, induction therapy, survival.

Received: June 5, 2018

Accepted: December 3, 2018

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REFERENCES

  1. Teras LR, DeSantis CE, Cerhan JR, et al. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA: Cancer J Clin. 2016;66(6):443–59. doi: 10.3322/caac.21357.

  2. Tilly H, Vitolo U, Walewski J, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii78–82. doi: 10.1093/annonc/mds273.

  3. Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematology. 2011;2011(1):498–505. doi: 10.1182/asheducation-2011.1.498.

  4. Coiffier B, Sarkozy C. Diffuse large B-cell lymphoma: R-CHOP failure-what to do? Hematology. 2016;2016(1):366–78. doi: 10.1182/asheducation-2016.1.366.

  5. Sant M, Minicozzi P, Mounier M, et al. Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study. Lancet Oncol. 2014;15(9):931–42. doi: 10.1016/S1470-2045(14)70282-7.

  6. Menard G, Dulong J, Nguyen TT, et al. Lenalidomide treatment restores in vivo T сell activity in relapsed/refractory FL and DLBCL. Blood. 2017;130(Suppl 1):729.

  7. Westin JR, Oki Y, Nastoupil L, et al. Lenalidomide and obinutuzumab with CHOP for newly diagnosed diffuse large B-cell lymphoma: final phase I/II results. Blood. 2017;130(Suppl 1):189.

  8. Петухов А.В., Маркова В.А., Моторин Д.В. и др. Получение CAR T-лимфоцитов, специфичных к CD19, и оценка их функциональной активности in vitro. Клиническая онкогематология. 2018;11(1):1–9. doi: 10.21320/2500-2139-2018-11-1-1-9.

    [Petukhov AV, Markova VA, Motorin DV, et al. Manufacturing of CD19 Specific CAR T-Cells and Evaluation of their Functional Activity in Vitro. Clinical oncohematology. 2018;11(1):1–9. doi: 10.21320/2500-2139-2018-11-1-1-9. (In Russ)]

  9. Sehn LH, Berry B, Chhanabhai M, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007;109(5):1857–61. doi: 10.1182/blood-2006-08-038257.

  10. International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329(14):987–94. doi: 10.1056/nejm199309303291402.

  11. Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17(4):1244. doi: 10.1200/jco.1999.17.4.1244.

  12. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86. doi: 10.1200/jco.2006.09.2403.

  13. Kurtz D, Scherer F, Jin M, et al. Development of a dynamic model for personalized risk assessment in large B-cell lymphoma. Blood. 2017;130(Suppl 1):826.

  14. Hamadani M, Hari PN, Zhang Y, et al. Early failure of frontline rituximab-containing chemoimmunotherapy in diffuse large B cell lymphoma does not predict futility of autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014;20(11):1729–36.

  15. Crump M, Kuruvilla J, Couban S, et al. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014;32(31):3490–6. doi: 10.1200/jco.2013.53.9593.

  16. Van Den Neste E, Schmitz N, Mounier N, et al. Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study. Bone Marrow Transplant. 2016;51(1):51–7. doi: 10.1038/bmt.2015.213.

  17. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800–8. doi: 10.1182/blood-2017-03-769620.

  18. Fang X, Xiu B, Yang Z, et al. The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma. Medicine (Baltimore). 2017;96(15):e6398. doi: 10.1097/MD.0000000000006398.

  19. Ключагина Ю.И., Соколова З.А., Барышникова М.А. Роль рецептора PD1 и его лигандов PDL1 и PDL2 в иммунотерапии опухолей. Онкопедиатрия. 2017;4(1):49–55. doi: 10.15690/onco.v4i1.1684.

    [Klyuchagina YuI, Sokolova ZA, Baryshnikova MA. Role of PD-1 Receptor and Its Ligands PD-L1 and PD-L2 in Cancer Immunotherapy. Onkopediatria. 2017;4(1):49–55. doi: 10.15690/onco.v4i1.1684. (In Russ)]

  20. Hayano A, Komohara Y, Takashima Y, et al. Programmed cell death ligand 1 expression in primary central nervous system lymphomas: a clinicopathological study. Anticancer Res. 2017;37(10):5655–66. doi: 10.21873/anticanres.12001.

  21. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–11. doi: 10.1038/35000501.

  22. Alizadeh AA, Gentles AJ, Alencar AJ, et al. Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. Blood. 2011;118(5):1350–8. doi: 10.1182/blood-2011-03-345272.

  23. Amin AD, Peters TL, Li L, et al. Diffuse large B-cell lymphoma: can genomics improve treatment options for a curable cancer? Mol Case Stud. 2017;3(3):a001719. doi: 10.1101/mcs.a001719.

Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region

LYMPHOID TUMORS , , , ,

VI Bakhtina1,2, IV Demko2, AN Narkevich2, DS Gushchin3

1 Regional Clinical Hospital, 3а Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

2 Professor VF Voyno-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

3 Norilsk Inter-District Hospital No. 1, Solnechnyi pr-d, 7a Norilsk, Russian Federation, 663300

For correspondence: Varvara Ivanovna Bakhtina, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022; Tel: +7(923)357-57-77; е-mail: doctor.gem@mail.ru

For citation: Bakhtina VI, Demko IV, Narkevich AN, Gushchin DS. Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region. Clinical oncohematology. 2016;9(4):413–419 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-413-419

ABSTRACT

Background & Aims. B-cellular chronic lymphocytic leukemia (CLL) is a disease with heterogeneous clinical manifestations and biological characteristics. The age of 70 % of patients is more than 65 years by the date of the diagnosis; most of them have several comorbidities. The aim of the study is to identify factors affecting the survival, as well as to determine causes of mortality in CLL patients (according to data from hematological hospitals of Krasnoyarsk Region).

Methods. In order to identify the most significant factors affecting the course and the outcome of CLL, a retrospective analysis of data on patients who died in hematological hospitals was carried out. 45 cases with the lethal outcome were registered within six years. All patients were under hematologist’s supervision after diagnosing the disease, and they were followed throughout the treatment period up to the lethal outcome.

Results. Тhe overall and progression-free survival depended, first of all, on the type of the first line therapy and its efficacy. The progression of the underlying disease and infectious complications became the main reason of the lethal outcome in CLL patients.

Conclusion. Most patients received ineffective treatment as first line therapy. The analysis of the comorbidities showed that a more effective chemotherapy could be performed with achievement of longer complete remissions.

Keywords: chronic lymphocytic leukemia, oncohematological diseases, comorbidities, survival, treatment.

Received: May 16, 2016

Accepted: June 17, 2016

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REFERENCES

  1. Gribben JG. How I treat CLL up front. Blood. 2010;115(2):187– doi: 10.1182/blood-2009-08-207126.
  2. Lee JS, Dixon DO, Kantarjian H, et al. Prognosis of chronic lymphocytic leukemia: a multivariate regression analysis of 325 untreated patients. Blood. 1987;69(3):929–36.
  3. Molica S. Infections in chronic lymphocytic leukemia: risks factors and impact on survival and treatment. Leuk Lymphoma. 1994;13(3–4):203–14. doi: 10.3109/10428199409056283.
  4. Albertsen PC, Moore DF, Shih W, et al. Impact of comorbidity on survival among men with localized prostate cancer. J Clin Oncol. 2011;29(10):1335–41. doi: 10.1200/jco.2010.31.2330.
  5. Etienne A, Esterni B, Charbonnier A, et al. Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia. Cancer. 2007;109(7):1376– doi: 10.1002/cncr.22537.
  6. Kos FT, Yazici O, Civelek B, et al. Evaluation of the effect of comorbidity on survival in pancreatic cancer by using “Charlson Comorbidity Index” and “Cumulative Illness Rating Scale”. Wien Klin Wochenschr. 2014;126(1–2):36– doi: 10.1007/s00508-013-0453-9.
  7. Della Porta MG, Malcovati L. Clinical relevance of extra-hematologic comorbidity in the management of patients with myelodysplastic syndrome. Haematologica. 2009;94(5):602– doi: 10.3324/haematol.2009.005702.
  8. Wang S, Wong ML, Hamilton N, et al. Impact of age and comorbidity on non-small-cell lung cancer treatment in older veterans. J Clin Oncol. 2012;30(13):1447–55. doi: 11200/jco.2011.39.5269.
  9. Strati P, Chaffe K, Achenbach S, et al. Comorbidity and cause of death in patients with chronic lymphocytic leukemia (CLL). Cancer Res. 2015;75(15): Abstract 5267. doi: 10.1158/1538-7445.am2015-5267.
  10. Goede V, Paula Cramer P, Busch R, et al. Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials. 2014;99(6):1095–100. doi: 10.3324/haematol.2013.096792.
  11. Thurmes P, Call T, Slager S, et al. Comorbid conditions and survival in unselected, newly diagnosed patients with chronic lymphocyticleukemia. Leuk Lymphoma. 2008;49(1):49–56. doi: 10.1080/10428190701724785.
  12. Linn BS, Linn MW, Gurel L. Cumulative illness rating scale. J Am Geriatr Soc. 1968;16(5):622–6. doi: 10.1111/j.1532-5415.1968.tbx.
  13. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. 2010;376(9747):1164–74. doi: 10.1016/S0140-6736.
  14. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83. doi: 10.1016/0021-9681(87)90171-8.
  15. Anaissie EJ, Kontoyiannis DP, O’Brien S, et al. Infections in patients with chronic lymphocytic leukemia treated with fludarabine. Ann Intern Med. 1998;129(7):559– doi: 10.7326/0003-4819-129-7-199810010-00010.
  16. Badoux XC, Keating MJ, Wang X, et al. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL. 2011;117(11):3016–24. doi: 10.1182/blood-2010-08-304683.
  17. Catovsky D, Richards S, Matutes E, et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007;370(9583):230–9. doi: 10.1016/s0140-6736(07)61125-8.
  18. Bouvet E, Borel C, Oberic L, et al. Impact of dose intensity on outcome of fludarabine, cyclophosphamide, and rituximab regimen given in the first-line therapy for chronic lymphocytic leukemia. 2013;98(1):65–70. doi: 10.3324/haematol.2012.070755.
  19. Miller MD, Paradis CF, Houck PR, et al. Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res. 1992;41(3):237–48. doi: 10.1016/0165-1781(92)90005-n.
  20. Parmlee PA, Thuras PD, Katz IR, et al. Validation of Cumulative Index Rating Scale in a geriatric residential population. J Am Geriatr Soc. 1995;43(2):130–7. doi: 10.1111/j.1532-5415.1995.tb06377.x.
  21. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis. 1987;40(5):373–83. doi: 1016/0021-9681(87)90171-8.

Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region

LYMPHOID TUMORS , , , ,

VI Bakhtina1,2, IV Demko2, AN Narkevich2, DS Gushchin3

1 Regional Clinical Hospital, 3а Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

2 Professor VF Voyno-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

3 Norilsk Inter-District Hospital No. 1, Solnechnyi pr-d, 7a Norilsk, Russian Federation, 663300

For correspondence: Varvara Ivanovna Bakhtina, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022; Tel: +7(923)357-57-77; е-mail: doctor.gem@mail.ru

For citation: Bakhtina VI, Demko IV, Narkevich AN, Gushchin DS. Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region. Clinical oncohematology. 2016;9(4):413–419 (In Russ).

DOI: http://dx.doi.org/10.21320/2500-2139-2016-9-4-413-419

ABSTRACT

Background & Aims. B-cellular chronic lymphocytic leukemia (CLL) is a disease with heterogeneous clinical manifestations and biological characteristics. The age of 70 % of patients is more than 65 years by the date of the diagnosis; most of them have several comorbidities. The aim of the study is to identify factors affecting the survival, as well as to determine causes of mortality in CLL patients (according to data from hematological hospitals of Krasnoyarsk Region).

Methods. In order to identify the most significant factors affecting the course and the outcome of CLL, a retrospective analysis of data on patients who died in hematological hospitals was carried out. 45 cases with the lethal outcome were registered within six years. All patients were under hematologist’s supervision after diagnosing the disease, and they were followed throughout the treatment period up to the lethal outcome.

Results. Тhe overall and progression-free survival depended, first of all, on the type of the first line therapy and its efficacy. The progression of the underlying disease and infectious complications became the main reason of the lethal outcome in CLL patients.

Conclusion. Most patients received ineffective treatment as first line therapy. The analysis of the comorbidities showed that a more effective chemotherapy could be performed with achievement of longer complete remissions.

Keywords: chronic lymphocytic leukemia, oncohematological diseases, comorbidities, survival, treatment.

Received: May 16, 2016

Accepted: June 17, 2016

Read in PDF (RUS) pdficon

REFERENCES

  1. Gribben JG. How I treat CLL up front. Blood. 2010;115(2):187– doi: 10.1182/blood-2009-08-207126.
  2. Lee JS, Dixon DO, Kantarjian H, et al. Prognosis of chronic lymphocytic leukemia: a multivariate regression analysis of 325 untreated patients. Blood. 1987;69(3):929–36.
  3. Molica S. Infections in chronic lymphocytic leukemia: risks factors and impact on survival and treatment. Leuk Lymphoma. 1994;13(3–4):203–14. doi: 10.3109/10428199409056283.
  4. Albertsen PC, Moore DF, Shih W, et al. Impact of comorbidity on survival among men with localized prostate cancer. J Clin Oncol. 2011;29(10):1335–41. doi: 10.1200/jco.2010.31.2330.
  5. Etienne A, Esterni B, Charbonnier A, et al. Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia. Cancer. 2007;109(7):1376– doi: 10.1002/cncr.22537.
  6. Kos FT, Yazici O, Civelek B, et al. Evaluation of the effect of comorbidity on survival in pancreatic cancer by using “Charlson Comorbidity Index” and “Cumulative Illness Rating Scale”. Wien Klin Wochenschr. 2014;126(1–2):36– doi: 10.1007/s00508-013-0453-9.
  7. Della Porta MG, Malcovati L. Clinical relevance of extra-hematologic comorbidity in the management of patients with myelodysplastic syndrome. Haematologica. 2009;94(5):602– doi: 10.3324/haematol.2009.005702.
  8. Wang S, Wong ML, Hamilton N, et al. Impact of age and comorbidity on non-small-cell lung cancer treatment in older veterans. J Clin Oncol. 2012;30(13):1447–55. doi: 11200/jco.2011.39.5269.
  9. Strati P, Chaffe K, Achenbach S, et al. Comorbidity and cause of death in patients with chronic lymphocytic leukemia (CLL). Cancer Res. 2015;75(15): Abstract 5267. doi: 10.1158/1538-7445.am2015-5267.
  10. Goede V, Paula Cramer P, Busch R, et al. Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials. 2014;99(6):1095–100. doi: 10.3324/haematol.2013.096792.
  11. Thurmes P, Call T, Slager S, et al. Comorbid conditions and survival in unselected, newly diagnosed patients with chronic lymphocyticleukemia. Leuk Lymphoma. 2008;49(1):49–56. doi: 10.1080/10428190701724785.
  12. Linn BS, Linn MW, Gurel L. Cumulative illness rating scale. J Am Geriatr Soc. 1968;16(5):622–6. doi: 10.1111/j.1532-5415.1968.tbx.
  13. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. 2010;376(9747):1164–74. doi: 10.1016/S0140-6736.
  14. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83. doi: 10.1016/0021-9681(87)90171-8.
  15. Anaissie EJ, Kontoyiannis DP, O’Brien S, et al. Infections in patients with chronic lymphocytic leukemia treated with fludarabine. Ann Intern Med. 1998;129(7):559– doi: 10.7326/0003-4819-129-7-199810010-00010.
  16. Badoux XC, Keating MJ, Wang X, et al. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL. 2011;117(11):3016–24. doi: 10.1182/blood-2010-08-304683.
  17. Catovsky D, Richards S, Matutes E, et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007;370(9583):230–9. doi: 10.1016/s0140-6736(07)61125-8.
  18. Bouvet E, Borel C, Oberic L, et al. Impact of dose intensity on outcome of fludarabine, cyclophosphamide, and rituximab regimen given in the first-line therapy for chronic lymphocytic leukemia. 2013;98(1):65–70. doi: 10.3324/haematol.2012.070755.
  19. Miller MD, Paradis CF, Houck PR, et al. Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res. 1992;41(3):237–48. doi: 10.1016/0165-1781(92)90005-n.
  20. Parmlee PA, Thuras PD, Katz IR, et al. Validation of Cumulative Index Rating Scale in a geriatric residential population. J Am Geriatr Soc. 1995;43(2):130–7. doi: 10.1111/j.1532-5415.1995.tb06377.x.
  21. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis. 1987;40(5):373–83. doi: 1016/0021-9681(87)90171-8.