efficacy

Ibrutinib as First-Line Therapy in High-Risk Chronic Lymphocytic Leukemia: Case Reports

AUTOIMMUNE THROMBOCYTOPENIA , ,

NV Kurkina, EA Repina

NP Ogarev National Research Mordovia State University, 68 Bolshevistskaya str., Saransk, Russian Federation, 430005

For correspondence: Nadezhda Viktorovna Kurkina, MD, PhD, 26А Ul’yanova str., Saransk, Russian Federation, 430032; Tel.: +7(927)172-48-63; e-mail: nadya.kurckina@yandex.ru

For citation: Kurkina NV, Repina EA. Ibrutinib as First-Line Therapy in High-Risk Chronic Lymphocytic Leukemia: Case Reports. Clinical oncohematology. 2021;14(4):488–95. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-488-495

ABSTRACT

In the selection of the optimal specific therapy in chronic lymphocytic leukemia (CLL), a crucial role is played by the determination of risk groups. The CLL International Prognostic Index takes account of unfavorable del(17p), del(11q) cytogenetic abnormalities, and/or TP53 gene mutations as well as the mutation status of immunoglobulin heavy chain variable region genes (IGHV). The absence of IGHV gene mutations is often associated with such prognostically unfavorable genetic markers as del(17p), del(11q), trisomy 12, and TP53 mutation. The combinations of this kind affect the prognosis and overall survival rate. Besides, in high-risk CLL the efficacy of therapy is rather low and the development of refractoriness is possible. In such patients the use of Bruton tyrosine kinase inhibitor as first-line therapy considerably increases the probability of long-term remission. The present paper provides the analysis of clinical and hematological efficacy and tolerance of ibrutinib as first-line therapy in high-risk CLL. Ibrutinib shows high efficacy and low toxicity. The use of ibrutinib as first-line therapy effectively reduces the probability of CLL progression, which is especially critical in high-risk patients, i.e., with 17p deletion and TP53 gene mutation.

Keywords: chronic lymphocytic leukemia, high-risk group, 17p deletion, TP53 gene mutation, ibrutinib, efficacy, toxicity.

Received: March 15, 2021

Accepted: August 30, 2021

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Wierda WG, Byrd JC, Abramson JS, et al. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 4.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18(2):185–217. doi: 10.6004/jnccn.2020.0006.
  2. Hallek MJ, Cheson BD, Catovsky D, Caligaris-Cappio F. IwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745–60. doi: 1182/blood-2017-09-806398.
  3. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В. Поддубной, В.Г. Савченко. М.: Буки Веди, 2018. С. 179–200.
    [Poddubnaya IV, Savchenko VG, eds. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevanii. (Russian clinical guidelines on diagnosis and treatment of lymphoproliferative disorders.) Moscow: Buki Vedi Publ.; 2018. 179–200. (In Russ)]
  4. Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: Updated results of the CLL8 trial. Blood. 2016;127(2):208–15. doi: 1182/blood-2015-06-651125.
  5. Thompson PA, Tam CS, O’Brien SM, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV–mutated chronic lymphocytic leukemia. 2016;127(3):303–9. doi: 10.1182/blood-2015-09-667675.
  6. 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. Lancet. 2010;376(9747):1164–74. doi: 10.1016/S0140-6736(10)61381-5.
  7. International CLL-IPI working group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016;17(6):779–90. doi: 10.1016/S1470-2045(16)30029-8.
  8. Pflug N, Bahlo J, Shanafelt T, Eichhorst B. Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia. Blood. 2014;12(4):49–62. doi: 1182/blood-2014-02-556399.
  9. Zenz T, Eichhorst B, Busch R, et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol. 2010;28(29):4473–9. doi: 10.1200/JCO.2009.27.8762.
  10. Rossi D, Khiabanian H, Spina V, et al. Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia. 2014;123(14):2139–47. doi: 10.1182/blood-2013-11-539726.
  11. Никитин Е.А., Судариков А.Б. Хронический лимфолейкоз высокого риска: история, определение, диагностика и лечение. Клиническая онкогематология. 2013;6(1):59–67.
    [Nikitin EA, Sudarikov AB. High­risk chronic lymphocytic leukemia: history, definition, diagnosis, and management. Klinicheskaya onkogematologiya. 2013;6(1):59–67. (In Russ)]
  12. Strati P, Shanafelt TD. Monoclonal B-cell lymphocytosis and early-stage chronic lymphocytic leukemia: Diagnosis, natural history, and risk stratification. Blood. 2015;126(4):454–62. doi: 10.1182/blood-2015-02-585059.
  13. Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425–37. doi: 10.1056/NEJMoa1509388.
  14. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL. N Engl J Med. 2018;379(26):2517–28. doi: 10.1056/NEJMoa1812836.

Efficacy, Safety, and Tolerance of Gemtuzumab Ozogamicin Combined with FLAG/FLAG-Ida or Azacitidine in Relapsed/Refractory Acute Myeloblastic Leukemia

AUTOIMMUNE THROMBOCYTOPENIA , , , , ,

IG Budaeva, DV Zaitsev, AA Shatilova, EN Tochenaya, AV Petrov, RI Vabishchevich, DV Motorin, RSh Badaev, DB Zammoeva, VV Ivanov, SV Efremova, KV Bogdanov, YuV Mirolyubova, TS Nikulina, YuA Alekseeva, AYu Zaritskey, LL Girshova

VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

For correspondence: Irina Garmaevna Budaeva, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; Tel.: +7(931)351-07-06; e-mail: irina2005179@mail.ru

For citation: Budaeva IG, Zaitsev DV, Shatilova AA, et al. Efficacy, Safety, and Tolerance of Gemtuzumab Ozogamicin Combined with FLAG/FLAG-Ida or Azacitidine in Relapsed/Refractory Acute Myeloblastic Leukemia. Clinical oncohematology. 2021;14(3):299–307. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-299-307

ABSTRACT

Aim. To assess the efficacy, safety, and tolerance of gemtuzumab ozogamicin (GO) combined with FLAG/FLAG-Ida chemotherapy or azacitidine in patients with relapsed/refractory acute myeloblastic leukemia (AML) in clinical practice.

Materials & Methods. The study included 32 patients (16 men and 16 women). The median age was 44 years (range 23–83 years). Among them there were 15 (46.8 %) patients with refractory and 17 (53.2 %) patients with relapsed AML. GO combined with FLAG/FLAG-Ida was administered to 15 (46.8 %) patients, whereas 17 (53.2 %) patients were treated with GO and azacitidine combination. Therapy safety was assessed according to CTCAE v. 5.0.

Results. Overall response rate including complete remission (CR), CR MRD–, CR with incomplete hematologic recovery, and morphologic leukemia-free status was 59.4 % (19/32). Refractoriness was observed in 31.25 % (10/32) of patients. Early mortality was 9.4 % (3/32). Overall response was 64.7 % (11/17) in the azacitidine and 53.3 % (8/15) in the FLAG/FLAG-Ida groups. In 4 (80 %) out of 5 patients with prior to FLAG treatment refractoriness, the response was achieved after GO + azacitidine therapy. In 58.9 % (10/17) of patients who received GO + azacitidine therapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be performed. The incidence of GO infusion complications in the tested groups did not significantly differ (p = 0.72) and was 46.7 % (7/15) (40 % with grade 1/2 and 6.7 % with grade 3) in the GO + FLAG/FLAG-Ida group and 35.3 % (6/17) (29.4 % with grade 1/2 and 5.9 % with grade 4) in the GO + azacitidine group. In the GO + FLAG/FLAG-Ida group 5 (33.3 %) patients experienced serious adverse events (SAE) of sepsis. In the GO + azacitidine group SAEs were reported in 6 (35.3 %) patients: 4 (66.6 %) with sepsis, 1 (16.7 %) with acute cardiovascular failure, and 1 (16.7 %) with acute respiratory failure. The median (range) duration was 23 (10–39) days for neutropenia grade 4, 24 (11–38) days for neutropenia grade 3, 21 (11–41) days for thrombocytopenia grade 4, 26 (16–45) days for thrombocytopenia grade 3, and 25 (22–45) days for thrombocytopenia grade 1/2. Thrombocytopenia duration was longer in patients with GO + FLAG/FLAG-Ida therapy, however, no significant differences were identified. No cases of veno-occlusive liver disease were reported. Median overall survival (OS) for both groups (n = 32) was 31.4 months, median disease-free survival (n = 21) was 13.3 months. In the group of patients with effective treatment, the median OS was not reached. In non-responders, it was 18 months (p = 0.0442).

Conclusion. GO combined with FLAG/FLAG-Ida chemotherapy or azacitidine proved effective in relapsed/refractory AML patients. Remission did not appear to be associated with ELN risk, gender, age, CD33 expression, number of prior therapy lines, or number of relapses. GO + azacitidine combination showed efficacy, safety, and good tolerance in patients with prior high-dose chemotherapy refractoriness as well as low ECOG performance status. That allowed for the subsequent allo-HSCT administration to these patients. There was no significant difference between the groups of patients in the incidence of hematologic, non-hematologic toxicity, and time to hematologic recovery. Thrombocytopenia duration was longer in patients with GO + FLAG/FLAG-Ida therapy which is consistent with literature data. GO-based effective treatment in relapsed/refractory AML considerably improves OS: during 36 months of follow-up the median was not reached.

Keywords: acute myeloblastic leukemia, relapse, refractoriness, gemtuzumab ozogamicin, FLAG/FLAG-Ida regimens, azacitidine, efficacy, safety, toxicity.

Received: February 5, 2021

Accepted: May 15, 2021

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Wang ES, Aplenc R, Chirnomas D, et al. Safety of gemtuzumab ozogamicin as monotherapy or combination therapy in an expanded-access protocol for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2020;61(12):1965–2973. doi: 10.1080/10428194.2020.1742897.
  2. Dombret H, Gardin C. An update of current treatments for adult acute myeloid leukemia. Blood. 2016;127(1):53–61. doi: 10.1182/blood-2015-08-604520.
  3. Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016;6(7):e441. doi: 10.1038/bcj.2016.50.
  4. Sievers EL, Larson RA, Stadtmauer EA, et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001;19(13):3244–54. doi: 10.1200/JCO.2001.19.13.3244.
  5. Zein N, Poncin M, Nilakantan R, et al. Calicheamicin gamma 1I and DNA: molecular recognition process responsible for site-specificity. Science. 1989;244(4905):697–9. doi: 10.1126/science.2717946.
  6. Linenberger ML. CD33-directed therapy with gemtuzumab ozogamicin in acute myeloid leukemia: progress in understanding cytotoxicity and potential mechanisms of drug resistance. Leukemia. 2005;19(2):176–82. doi: 10.1038/sj.leu.2403598.
  7. Sievers EL, Appelbaum FR, Spielberger RT, et al. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: A phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood. 1999;93(11):3678–84. doi: 10.1182/blood.v93.11.3678.411k24_3678_3684.
  8. Bross PF, Beitz J, Chen G, et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res. 2001;7(6):1490–6.
  9. Deangelo DJ, Liu D, Stone R, et al. Preliminary report of a phase 2 study of gemtuzumab ozogamicin in combination with cytarabine and daunorubicin in patients < 60 years of age with de novo acute myeloid leukemia. Proceed Am Soc Clin Oncol. 2003: Abstract 2325.
  10. Petersdorf SH, Kopecky KJ, et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013;121(24):4854–60. doi: 10.1182/blood-2013-01-466706.
  11. Caron PC, Jurcic JG, Scott AM, et al. A phase 1B trial of humanized monoclonal antibody M195 (anti-CD33) in myeloid leukemia: specific targeting without immunogenicity. Blood. 1994;83(7):1760–8. doi: 10.1182/blood.v83.7.1760.bloodjournal8371760.
  12. Castaigne S, Pautas C, Terre C, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012;379(9825):1508–16. doi: 10.1016/S0140-6736(12)60485-1.
  13. Lambert J, Pautas С. Terre Ch, et al. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019;104(1):113–9. doi: 10.3324/haematol.2018.188888.
  14. Amadori S, Suciu S, Selleslag D, et al. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016;34(9):972–9. doi: 10.1200/jco.2015.64.0060.
  15. Taksin AL, Legrand O, Raffoux E, et al. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia. 2007;21(1):66–71. doi: 10.1038/sj.leu.2404434.
  16. Debureaux P-E, Labopin М, Mamez A-C, et al. Fractionated gemtuzumab ozogamicin in association with high dose chemotherapy: a bridge to allogeneic stem cell transplantation in refractory and relapsed acute myeloid leukemia. Bone Marrow Transplant. 2019;55(2):452–60. doi: 10.1038/s41409-019-0690-2.
  17. Chevallier P, Delaunay J, Turlure P, et al. Long-term disease-free survival after gemtuzumab, intermediate-dose cytarabine, and mitoxantrone in patients with CD33(+) primary resistant or relapsed acute myeloid leukemia. J Clin Oncol. 2008;26(32):5192–7. doi: 10.1200/jco.2007.15.9764.
  18. Medeiros BC, Tanaka TN, Balaian L, et al. A Phase I/II Trial of the Combination Azacitidine and Gemtuzumab Ozogamicin for Treatment of Relapsed Acute Myeloid Leukemia. Clin Lymphoma Myel Leuk. 2018;18(5):346–352.e5. doi: 10.1016/j.clml.2018.02.017.
  19. Walter RB, Medeiros BC, Gardner KM, et al. Gemtuzumab ozogamicin in combination with vorinostat and azacitidine in older patients with relapsed or refractory acute myeloid leukemia: a phase I/II study. Haematologica. 2013;99(1):54–9. doi: 10.3324/haematol.2013.096545.
  20. Arain S, Christian S, Patel PR. Safety and efficacy of gemtuzumab ozogamicin and venetoclax in patients with relapsed or refractory CD33+ acute myeloid leukemia: A phase Ib study. J Clin Oncol. 2020;38(15_suppl):TPS7566. doi: 10.1200/JCO.2020.38.15_suppl.TPS7566.
  21. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. 2016;127(20):2391–405. doi: 10.1182/blood-2016-03-643544.
  22. Dohner H, Elihu H, Estey EH, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453–74. doi: 10.1182/blood-2009-07-235358.
  23. Зайцев Д.В., Гиршова Л.Л., Иванов В.В. и др. Гемтузумаб озогамицин в лечении пациентов с рефрактерным течением острого миелоидного лейкоза, находящихся в критическом состоянии (описание 3 клинических наблюдений). Клиническая онкогематология. 2020;13(1):67–74. doi: 10.21320/2500-2139-2020-13-1-67-74.
    [Zaitsev DV, Girshova LL, Ivanov VV, et al. Gemtuzumab Ozogamicin in the Treatment of Critical Patients with Refractory Acute Myeloid Leukemia (3 Case Reports). Clinical oncohematology. 2020;13(1):67–74. doi: 10.21320/2500-2139-2020-13-1-67-74. (In Russ)]
  24. Stone RM, Moser B, Sanford B, et al. High dose cytarabine plus gemtuzumab ozogamicin for patients with relapsed or refractory acute myeloid leukaemia: Cancer and Leukaemia Group B study 19902. Leuk Res. 2011;35(3):329–33. doi: 10.1016/j.leukres.2010.07.017.
  25. Hosono N, Ookura M, Araie H, et al. Clinical outcomes of gemtuzumab ozogamicin for relapsed acute myeloid leukemia: single-institution experience. Int J Hematol. 2020;113(3):362–9. doi: 10.1007/s12185-020-03023-4.
  26. Будаева И.Г., Гиршова Л.Л., Овсянникова Е.Г. и др. Прогнозирование эффективности режима FLAG ± Ida у пациентов с рецидивами и рефрактерным течением острых миелоидных лейкозов. Клиническая онкогематология. 2019;12(3):289–96. doi: 10.21320/2500-2139-2019-12-3-289-296.
    [Budaeva IG, Girshova LL, Ovsyannikova EG, et al. Prediction of FLAG ± Ida Regimen Efficacy in Patients with Relapsed/Refractory Acute Myeloid Leukemia. Clinical oncohematology. 2019;12(3):289–96. doi: 10.21320/2500-2139-2019-12-3-289-296. (In Russ)]
  27. Chantepie SP, Reboursiere E, Mear JB, et al. Gemtuzumab ozogamicin in combination with intensive chemotherapy in relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2015;56(8):2326–30. doi: 3109/10428194.2014.986478.
  28. Burnett AK, Russell NH, Hills RK, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012;30(32):3924–31. doi: 10.1200/jco.2012.42.2964.

 

 

Efficacy and Toxicity of Therapy for Patients with Intermediate-Risk Hodgkin’s Lymphoma: Results of Multicenter Randomized Study

AUTOIMMUNE THROMBOCYTOPENIA, LYMPHOID TUMORS , , ,

IA Kryachok1, AA Amdiev2, IB Titorenko1, EM Aleksik1, EO Ul’yanchenko1, OI Novosad1, ES Filonenko1, MI Kasich2, MYa Kiseleva2

1 National Cancer Institute, 33/43 Lomonosova str., Kyiv, Ukraine, 03022

2 V.M. Efetov Crimean National Clinical Oncology Dispensary, 49a Bespalova str., Simferopol, Russian Federation, 295023

For correspondence: Alim Anvarovich Amdiev, 49a Bespalova str., Simferopol, Russian Federation, 295023; Tel.: +38(0652)60-22-09; e-mail: amdiev@gmail.com

For citation: Kryachok IA, Amdiev AA, Titorenko IB, et al. Efficacy and Toxicity of Therapy for Patients with Intermediate-Risk Hodgkin’s Lymphoma: Results of Multicenter Randomized Study. Clinical oncohematology. 2015;8(3):281–6 (In Russ).

ABSTRACT

Objective. To study the efficacy and toxicity of various treatment schemes for patients with intermediate-risk Hodgkin’s lymphoma (HL).

Methods. This article presents an analysis of the immediate results of complex treatment of 103 intermediate-risk HL patients (stage IIA and IIB with one or more unfavorable prognostic factors), who have been treated at the National Cancer Institute (Kyiv) and the Crimean Oncology Dispensary (Simferopol) from 2009 to 2014 (study group). Patients were divided into two study groups and treated with 6xBEACOPP-esc or 2xBEACOPP-esc + 4xABVD, followed by radiotherapy on the affected areas at a dose of 30–36 Gy in both groups. The control group included 53 patients who received treatment according to the 6xABVD scheme, followed by radiotherapy on the affected areas at a dose of 30–36 Gy over the period from 2000 to 2008. The immediate efficiency of the therapy, as well as its toxicity was evaluated.

Results. The study results demonstrated that treatment of the intermediate-risk HL patients that included 6xBEACOPP-esc and 2xBEACOPP-esc + 4xABVD proved to be an effective approach. Overall immediate efficacy of 2xBEACOPP-esc + 4xABVD protocol with subsequent radiation therapy was 95.83 %, and that of the 6xBEACOPP-esc was 96.36 %, which was significantly higher than the efficacy in the control group (83.02 %; p < 0.05). The toxicity level of the therapy was lower in the 2xBEACOPP-esc + 4xABVD group than that in the 6xBEACOPP-esc group (63.19 % and 83.03 %, respectively, p < 0.001).

Conclusion. Treatment of patients with intermediate-risk HL with 2xBEACOPP-esc + 4xABVD is comparable to that with 6xBEACOPP-esc, but it demonstrates a better toxicity profile.

Keywords: Hodgkin’s lymphoma, chemotherapy, efficacy, toxicity.

Received: March 31, 2015

Accepted: May 31, 2015

Read in PDF (RUS)pdficon

REFERENCES

  1. Diehl V, ed. 25 Years German Hodgkin Study Group. Medizin & Wissen; 2004.
  2. Демина Е.А. Лимфома Ходжкина: от Томаса Ходжкина до наших дней. Клиническая онкогематология. 2008;1(2):114–8.
    [Demina EA. Hodgkin’s lymphoma: from Thomas Hodgkin till present days. Klinicheskaya onkogematologiya. 2008;1(2):114–8. (In Russ)]
  3. Diehl V, Franklin J, Pfreundschuh M, et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med. 2003;348(24):2386–95. doi: 10.1056/nejmoa022473.
  4. Федоренко З.П., Гайсенко А.В., Гулак Л.О. [та ін.] Рак в Украiні, 2009–2010. Захворюваність, смертність, показники діяльності онкологічноi служби. Бюл. Національного канцер-ре’стру Украiни. 2011;12:73–4.
    [Fedorenko ZP, Gaisenko AV, Gulak LO, et al. Cancer in Ukraine, 2009–2010. Morbidity and mortality rates and cancer service performance indicators. Byulleten’ Natsіonal’nogo kantser-re’stru Ukraini. 2011;12:73–4. (In Ukr.)]
  5. Engert A, Diehl V, Franklin J, et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin’s lymphoma: 10 years of follow-up of the GHSG HD9 Study. J Clin Oncol. 2009;27(27):4548–54. doi: 10.1200/jco.2008.19.8820.
  6. Lister TA. Staging for Hodgkin’s disease. Semin Oncol. 1990;17(6):696–703.
  7. Aleman BM, Raemaekers JM, Tirelli U, et al. Involved-field radiotherapy for advanced Hodgkin’s lymphoma. N Engl J Med. 2003;348(24):2396–406. doi: 10.1056/nejmoa022628.
  8. Bonadonna G, Zucali R, Monfardini S, et al. Combination chemotherapy of Hodgkin’s disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer. 1975;36(1):252–9. doi: 10.1002/1097-0142(197507)36:1<252::aid-cncr2820360128>3.0.co;2-7.
  9. Bonadonna G, Bonfante V, Viviani S, et al. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin’s disease: long-term results. J Clin Oncol. 2004;22(14):2835–41. doi: 10.1200/jco.2004.12.170.
  10. Engert A, Plutschow A, Eich HT, et al. Reduced Treatment Intensity in Patients with Early-Stage Hodgkin’s Lymphoma. N Engl J Med. 2010;363(7):640–52. doi: 10.1056/nejmoa1000067.
  11. Horning SJ. Risk, cure and complications in advanced Hodgkin disease. ASH Educ Program. 2007;1:197–203. doi: 10.1182/asheducation-2007.1.197.
  12. Horning SJ, Hoppe RT, Advani R, et al. Efficacy and late effects of Stanford V chemotherapy and radiotherapy in untreated Hodgkin’s disease: mature data in early and advanced stage patients. Blood. 2004;104:92a, abstract 308.
  13. Diehl V, Haverkamp H, Mueller RP, et al. Eight Cycles of BEACOPP escalated compared with 4 cycles of BEACOPP escalated followed by 4 cycles of BEACOPP baseline with or without radiotherapy in patients in advanced stage Hodgkin lymphoma (HL): final analysis of the randomised HD12 trial of the German Hodgkin Study Group (GHSG). Blood. 2008;112(11): Abstract 1558.
  14. Sieber M, Bredenfeld H, Josting А, et al. 14-day variant of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone regimen in advanced stage Hodgkin’s lymphoma: results of a pilot study of the German Hodgkin’s Lymphoma Study Group. J Clin Oncol. 2003;21(9):1734–9. doi: 10.1200/jco.2003.06.028.
  15. Engert A, Haverkamp H, Kobe C, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trail): a randomised, open-label, phase 3 non-inferiority trail. The Lancet. 2012;379(9828):1791–9. doi: 10.1016/s0140-6736(11)61940-5.
  16. 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.
  17. Engert A, Franklin J, Eich HT, et al. Two cycles of ABVD plus extended field radiotherapy is superior to radiotherapy alone in early-favorable Hodgkin lymphoma: final results of the GHSG HD7 Trial. J Clin Oncol. 2007;10(10):3495–502. doi: 10.1200/jco.2006.07.0482.
  18. Engert A, Diehl V, Pluetschow A, et al. Two cycles of ABVD followed by involved field radiotherapy with 20 Gray (Gy) the new standard of care in the treatment of patients with early-stage Hodgkin lymphoma: final analysis of the randomized German Hodgkin Study Group (GHSG) HD10. Blood. 2009;114: Abstract 716.
  19. Diehl V, Franklin J, Pfistner B, Engert A. German Hodgkin Study Group. Ten-year results of a German Hodgkin Study Group randomized trial of standart and increased dose BEACOPP chemotherapy for advanced Hodgkin lymphoma (HD9). J Clin Oncol (Meeting Abstracts). 2007;25(Suppl 18):LBA8015.

Genfatinib® therapy for chronic-phase chronic myeloid leukemia in routine clinical practice

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF MYELOID MALIGNANCIES , , ,

T.V. Chagorova1, V.V. Yablokova2, P.A. Borkina3, and N.A. Pryanikova3

1 Regional Oncology Clinic, Penza, Russian Federation

2 Yaroslavl Regional Clinical Hospital, Yaroslavl, Russian Federation

3 Moscow Representative Office of GENFA LTD (United Kingdom), Moscow, Russian Federation

ABSTRACT

The article describes the outcomes of Genfatinib® therapy in routine clinical practice at the Regional Oncology Clinic (Penza) and Yaroslavl Regional Clinical Hospital (Yaroslavl). 62 patients with chronic myeloid leukemia (chronic phase) were treated at the above institutions from April 2012 to April 2013. The patients were assigned into the following groups: the first treatment group, where Genfatinib® was prescribed as an initial therapy at the time of diagnosis of chronic-phase chronic myeloid leukemia; the second group, where Genfatinib® was prescribed after the initial therapy with Gleevek®. The main objectives were assessment of the Genfatinib® efficacy (rates of complete or partial clinico-hematological, cytogenetic, and molecular responses), toxicity, and safety. It was shown that Genfatinib® used after previous therapy with Gleevek® caused no negative influence of the rates of clinico-hematological, cytogenetic, and molecular responses. In the patients who received Genfatinib® as an initial therapy, the complete clinico-hematological and cytogenetic and molecular responses were achieved by 3–5 and 3–6 months of treatment, respectively. The spectrum of adverse events observed with Genfatinib® therapy was similar to the one of Gleevek®.

Keywords: chronic myeloid leukemia, chronic phase, Genfatinib®, efficacy, safety.

Read in PDF (RUS)pdficon

Refernces

  1. Туркина А.Г. Хронический миелолейкоз. Руководство по гематологии. М.: Ньюмед, 2003: 251–64. [Turkina A.G. Khronicheskiy miyeloleykoz. Rukovodstvo po gematologii (Chronic myeloid leukemia. Manual on hematology). M.: Nyumed, 2003: 251–64.]
  2. Хронический миелоидный лейкоз у взрослых. Национальный клини- ческий протокол. Кишинев, 2009: 7. [Khronicheskiy miyeloidnyy leykoz u vzroslykh. Natsionalnyy klinicheskiy protokol (Chronic myeloid leukemia in adults. National clinical protocol). Kishinev, 2009: 7]
  3. Туркина Г.А., Виноградова О.Ю., Хорошко Н.Д., Воробьев А.И. До- стижения в диагностике и лечении больных хроническим миелолейкозом в Российской Федерации (2004–2008 гг.). Бюлл. сибир. мед. 2008; 3: 76–80. Федерации (2004–2008 гг.). Бюлл. сибир. мед. 2008; 3: 76–80. [Turkina G.A., Vinogradova O.Yu., Khoroshko N.D., Vorobyev A.I. Dostizheniya v diagnostike i lechenii bolnykh khronicheskim miyeloleykozom v Rossiyskoy Federatsii (2004–2008 gg.) (Achievements in diagnosis and management of patients with chronic myeloid leukemia in Russian Federation (2004–2008). In: Bull. of Siber. med.). Byull. sibir. med. 2008; 3: 76–80]
  4. Виноградова О.Ю. Клиническая эволюция хронического миелолей- коза в процессе лечения ингибиторами тирозинкиназ: Автореф. дис. ¼ д-ра мед. наук. М., 2011: 7. [Vinogradova O.Yu. Klinicheskaya evolyutsiya khronicheskogo miyeloleykoza v protsesse lecheniya ingibitorami tirozinkinaz: Avtoref. dis. ¼ d-ra med. nauk (Clinical evolution of chronic myeloid leukemia during therapy with tyrosinekinase inhibitors: Author’s summary of dissertation for the degree of DSci). M., 2011: 7.]
  5. Виноградова О.Ю., Туркина А.Г., Хорошко Н.Д. Организация терапии хронического миелолейкоза. Первый общероссийский регистр больных хроническим миелолейкозом: анализ и перспективы. Журн. ONCOLOGY. RU® (Период. науч.-практ., реценз. электр. изд.) 2009: 1–17. [Vinogradova O.Yu., Turkina A.G., Khoroshko N.D. Organizatsiya terapii khronicheskogo miyeloleykoza. Pervyy obshcherossiyskiy registr bolnykh khronicheskim miyeloleykozom: analiz i perspektivy (Organization of therapy for chronic myeloid leukemia. First all-Russian register of patients with chronic myeloid leukemia: analysis and prospects. In: Journ. ONCOLOGY.RU® (Period. scientif-and-pract. peer-reveiwed ed.)). Zhurn. ONCOLOGY.RU® (Period. nauch.-prakt., retsenz. elektr. izd.) 2009: 1–17.]
  6. Куцев С.И. Генетический мониторинг таргетной терапии хрониче- ского миелоидного лейкоза: Автореф. дис. ¼ д-ра мед. наук. М., 2009: 3. [Kutsev S.I. Geneticheskiy monitoring targetnoy terapii khronicheskogo miyeloidnogo leykoza: Avtoref. dis. ¼ d-ra med. nauk (Genetic monitoring of target therapy for chronic myeloid leukemia: Author’s summary of dissertation for the degree of DSci). M., 2009: 3.]
  7. Стахина О.В., Туркина А.Г., Гусарова Г.А. и др. Отдаленные резуль- таты выживаемости больных в поздней хронической фазе Ph+ хрониче- ского миелолейкоза при лечении иматиниба мезилатом (Гливек®). Вестн. гематол. 2009; 5(2): 42. [Stakhina O.V., Turkina A.G., Gusarova G.A. i dr. Otdalennyye rezultaty vyzhivayemosti bolnykh v pozdney khronicheskoy faze Ph+ khronicheskogo miyeloleykoza pri lechenii imatiniba mezilatom (Glivek®) (Long-term survival of patients with late-stage chronic phase Ph+ chronic myeloid leukemia treated with imatinib mesylate (Gleevek®). In: Bull. of hematol.). Vestn. gematol. 2009; 5(2): 42.]
  8. Куцев С.И., Шатохин Ю.В. Влияние перерывов терапии иматинибом на достижение цитогенетического и молекулярного ответов у больных хроническим миелолейкозом. Казан. мед. журн. 2009; 90(6): 827–31. [Kutsev S.I., Shatokhin Yu.V. Vliyaniye pereryvov terapii imatinibom na dostizheniye tsitogeneticheskogo i molekulyarnogo otvetov u bolnykh khronicheskim miyeloleykozom (Impact of interruptions in imatinib therapy on achievement of cytogenetic and molecular responses in patients with chronic myeloid leukemia. In: Kazan. med. journ.). Kazan. med. zhurn. 2009; 90(6): 827–31.]
  9. Ковалева Л.Г., Соколова М.А., Виноградова О.Ю. и др. Результаты многоцентрового исследования терапии гливеком больных хроническим ми- елолейкозом в хронической фазе. Гематол. и трансфузиол. 2007; 52(2): 13–7. [Kovaleva L.G., Sokolova M.A., Vinogradova O.Yu. i dr. Rezultaty mnogo tsentrovogo issledovaniya terapii glivekom bolykh khronicheskim miyeloleykozom v khronicheskoy faze (Results of multicenter study of Gleevek therapy in patients with chronic phase chronic myeloid leukemia. In: Hematol. & transfusiol.). Gematol. i transfuziol. 2007; 52(2): 13–7.]