multiple myeloma

Retrospective Survival Analysis of Multiple Myeloma Patients after Autologous Hematopoietic Stem Cell Transplantation

AUTOIMMUNE THROMBOCYTOPENIA ,

II Kostroma1, AA Zhernyakova1, IM Zapreeva1, ZhYu Sidorova1, NYu Semenova1, EV Karyagina2, EI Stepchenkova3,4, SS Bessmeltsev1, AV Chechetkin1, SV Gritsaev1

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

3 Saint Petersburg State University, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

4 NI Vavilov Institute of General Genetics, Saint Petersburg branch, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Kostroma II, Zhernyakova AA, Zapreeva IM, et al. Retrospective Survival Analysis of Multiple Myeloma Patients after Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2021;14(1):73–9. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-73-79

ABSTRACT

Background. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an indispensable treatment stage in patients with newly diagnosed multiple myeloma (MM) who are, based on age and health status, eligible for high-dose chemotherapy with subsequent auto-HSCT. However, the issue of double (tandem) auto-HSCT feasibility remains unresolved.

Aim. To compare overall survival (OS) and progression-free survival (PFS) in MM patients after single and double (tandem) auto-HSCTs in clinical practice.

Materials & Methods. Retrospective analysis enrolled 83 MM patients divided into two groups: with single (n = 41) and double (n = 42) auto-HSCTs. Median age in groups 1 and 2 was 58 years (range 42–68) and 54 years (range 40–65), respectively. In these groups there were 16 (39 %) and 11 (26.2 %) patients ≥ 60 years old. The reference point of survival curve was the date of first (in group 1) and 2nd (in group 2) auto-HSCTs. In PFS assessment, completed event was the date of disease progression or relapse detection, including the biochemical one in case of specific therapy onset.

Results. Total number of patients with ≥ very good partial response before receiving auto-HSCT in group 1 was 23 (56.1 %), and in group 2 before receiving 2nd auto-HSCT it was 30 (71.4 %). Mel200 conditioning was administered to 53.7 % of patients in group 1. In group 2 this conditioning regimen was a priority in performing first auto-HSCT (83.3 % of patients) and was more rarely used in case of repeated transplantation (40.5 %). With median follow-up of 11 and 40.5 months in groups 1 and 2 no significant differences were identified either in median PFS (21 and 40 months; р = 0.154) or in median OS (not reached in both groups; p = 0.882). No differences between groups with respect to the time before relapse/progression or early relapse rate were observed.

Conclusion. Repeated auto-HSCT showed no additional antitumor effect. It can be accounted for by the lack of data on chromosome aberrations at the disease onset in most patients and by a small number of patients in the groups. Nevertheless, it was decided to limit the number of tandem auto-HSCTs and to perform 2nd transplantation mostly in case of late relapse/progression. New studies were initiated which will focus on the search of predictors associated with survival improvement in MM patients while performing double (tandem) auto-HSCTs.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, single auto-HSCT, double (tandem) auto-HSCTs, survival.

Received: July 15, 2020

Accepted: November 20, 2020

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Статистика Plumx английский

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Comorbidity and Personalized Treatment of Multiple Myeloma in Real Clinical Practice

AUTOIMMUNE THROMBOCYTOPENIA , ,

NV Skvortsova1, IB Kovynev1, KV Khalzov1, TI Pospelova1, IN Nechunaeva2

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

2 Municipal Clinical Hospital No. 2, 21 Polzunova str., Novosibirsk, Russian Federation, 630051

For correspondence: Nataliya Valer’evna Skvortsova, MD, PhD, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091; Tel.: 8(905)955-59-91; Fax: 8(383)279-94-06; e-mail: nata_sk78@mail.ru

For citation: Skvortsova NV, Kovynev IB, Khalzov KV, et al. Comorbidity and Personalized Treatment of Multiple Myeloma in Real Clinical Practice. Clinical oncohematology. 2020;13(3):322–34 (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-322-334

ABSTRACT

Aim. To study incidence and structure of comorbidity in multiple myeloma (MM) patients depending on their age; to determine its effect on overall survival, efficacy, and safety of the first-line therapy in real clinical practice.

Materials & Methods. Overall, 369 patients with newly diagnosed MM were enrolled in the trial from January 2012 to December 2017. Among them there were 134 men and 235 women hospitalized at the Unit of Hematology in the Novosibirsk Municipal Clinical Hospital No. 2. Median age of patients was 67 years (range 32–82 years).

Results. The analyzed patients were divided into three age groups: the first group of young/middle age (32–59 years) (n = 105), the second group of elderly patients (60–74 years) (n = 186), and the third group of old age (≥ 75 years) (n = 78). In each patient prior to chemotherapy the comorbidity spectrum was identified and CIRS-G, CCI, and MCI comorbidity scores were calculated. Patients with newly diagnosed MM in real clinical practice prove to have high and increasing with age comorbidity incidence (91 % in patients of young/middle age, 97,7 % and 100 % in patients of elderly and old age, respectively). Comorbidity significantly reduces overall survival (OS) of MM patients. Important OS predictors are rhythm and conduction disorder (odds ratio, OR, 2.762; p < 0.002), chronic pancreatitis (OR 1.864; p < 0.001), exogenous constitutive obesity (OR 1.948; p < 0.002), chronic obstructive pulmonary disease (OR 2.105; p < 0.021), chronic kidney disease, stage С4–С5 (OR 2.255; p < 0.003), and chronic heart failure, functional class II (OR 1.915; p < 0.002). Highest importance in predicting OS, efficacy, and tolerance to chemotherapy in MM patients is attached to MCI score (OR 3.771; p < 0.001). MM patients with high risk by MCI are characterized by lower rate and depth of response to the first-line therapy, shorter time before the first relapse, higher incidence of non-hematologic toxicity of grade ≥ 3, and therapy withdrawal or drug dose reduction.

Conclusion. Comorbidity assessment in MM patients is important for outcome prediction and treatment planning.

Keywords: multiple myeloma, comorbidity, comorbidity scores, overall survival, personalized treatment.

Received: April 2, 2020

Accepted: June 18, 2020

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  50. Labonte L, Iqbal T, Zaidi MA, et al. Utility of comorbidity assessment in predicting transplantation-related toxicity following autologous hematopoietic stem cell transplantation for multiple myeloma. Biol Blood Marrow Transplant. 2008;14(9):1039–44. doi: 10.1016/j.bbmt.2008.06.019.

Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Treatment with and without the Use of Granulocyte Colony-Stimulating Factor in Post-Transplantation Period

AUTOIMMUNE THROMBOCYTOPENIA ,

SV Gritsaev, II Kostroma, AA Zhernyakova, IM Zapreeva, VN Chebotkevich, SS Bessmeltsev, AV Chechetkin

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

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: 8(812)717-54-68; e-mail: obex@rambler.ru

For citation: Gritsaev SV, Kostroma II, Zhernyakova AA, et al. Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Treatment with and without the Use of Granulocyte Colony-Stimulating Factor in Post-Transplantation Period. Clinical oncohematology. 2020;13(3):289–94 (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-289-294

ABSTRACT

Background. There exist different data on how the administration of granulocyte colony-stimulating factor (G-CSF) after autologous hematopoietic stem cell transplantation (auto-HSCT) affects the duration of post-transplantation agranulocytosis in multiple myeloma (MM) patients.

Aim. To study the effect of G-CSF, administered after auto-HSCT to MM patients, on the duration of neutrophil engraftment, febrile neutropenia rate, and hospitalization duration.

Materials & Methods. The trial included 36 MM patients aged 42–69 years (median 59 years), 16 of which were not treated with G-CSF (1st group), and 20 patients received a single injection of 6 mg pegylated G-CSF on Day +4 or Day +5 (2nd group).

Results. Patients of the 1st group were significantly younger than patients of the 2nd group: median 55.5 and 61 years, respectively (p = 0.006). There were no differences with respect to the number of patients who previously received lenalidomide, the overall and very good partial response rate, the number of the first and repeated auto-HSCTs, and the number of melphalan conditioning regimens. The patients who received G-CSF engrafted neutrophils on day 11 (median) after auto-HSCT, i.e. earlier than patients without G-CSF administration who engrafted neutrophils on day 13 (p = 0.006). In the 1st group intravenous antibiotics were administered for a longer time than in the group with G-CSF: median 13 and 11 days, respectively (p = 0.04). In 2 patients from the group without G-CSF sepsis was diagnosed. G-CSF administration led to a shorter hospital stay: median 16 and 18 days in the 1st and 2nd groups, respectively (p = 0.08). There were no differences in the number of patients with febrile neutropenia.

Conclusion. G-CSF administration improves the course of the post-transplantation period in MM patients. The final decision on the feasibility of G-CSF administration after auto-HSCT can be made after more clinical observations are available.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, granulocyte colony-stimulating factor.

Received: January 14, 2020

Accepted: April 30, 2020

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REFERENCES

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  2. 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-S2-1-24.[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-S2-1-24. (In Russ)]

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  4. Грицаев С.В., Кузяева А.А., Бессмельцев С.С. Отдельные аспекты аутологичной трансплантации гемопоэтических стволовых клеток при множественной миеломе. Клиническая онкогематология. 2017;10(1):7–12. doi: 10.21320/2500-2139-2017-10-1-7-12.[Gritsaev SV, Kuzyaeva AA, Bessmel’tsev SS. Certain Aspects of Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma. Clinical oncohematology. 2017;10(1):7–12. doi: 10.21320/2500-2139-2017-10-1-7-12. (In Russ)]

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  8. Samaras P, Blickenstorfer M, Siciliano RD, et al. Pegfilgrastim reduces the length of hospitalization and the time to engraftment in multiple myeloma patients treated with melphalan 200 and auto-SCT compared with filgrastim. Ann Hematol. 2011;90(1):89– doi: 10.1007/s00277-010-1036-8.

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  10. Martinez-Cibrian N, Magnano L, Gutierrez-Garcia G, et al. At-home autologous stem cell transplantation in multiple myeloma with and without G-CSF administration: a comparative study. Bone Marrow Transplant. 2016;51(4):593–5. doi: 10.1038/bmt.2015.287.

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  12. Usmani SZ, Hoering A, Cavo M, et al. Clinical predictors of long-term survival in newly diagnosed transplant eligible multiple myeloma – an IMWG Research Project. Blood Cancer J. 2018;8(12):123. doi: 10.1038/s41408-018-0155-7.

  13. Hari P, Reece DE, Randhawa J, et al. Final outcomes of escalated melphalan 280 mg/m2 with amifostine cytoprotection followed autologous hematopoietic stem cell transplantation for multiple myeloma: high CR and VGPR rates do not translate into improved survival. Bone Marrow Transplant. 2019;54(2):293–9. doi: 10.1038/s41409-018-0261-y.

  14. Грицаев С.В., Кострома И.И., Жернякова А.А. и др. Опыт применения режима кондиционирования Thio/Mel перед трансплантацией аутологичных гемопоэтических стволовых клеток при множественной миеломе. Клиническая онкогематология. 2019;12(3):282–8. doi: 10.21320/2500-2139-2019-12-3-282-288.[Gritsaev SV, Kostroma II, Zhernyakova AA, et al. Experience with the Use of Thio/Mel Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma. Clinical oncohematology. 2019;12(3):282–8. doi: 10.21320/2500-2139-2019-12-3-282-288. (In Russ)]

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  18. Cho YK, Irby DJ, Li J, et al. Pharmacokinetic-pharmacodynamic model of neutropenia in patients with myeloma receiving high-dose melphalan for autologous stem cell transplant. CPT: Pharmacometr Syst Pharmacol. 2018;7(11):748–58. doi: 10.1002/psp4.12345.

  19. Кострома И.И., Жернякова А.А., Чубукина Ж.В. и др. Заготовка гемопоэтических стволовых клеток у больных множественной миеломой: влияние предшествующей аутоТГСК терапии леналидомидом и режима мобилизации. Клиническая онкогематология. 2018;11(2):192–7. doi: 10.21320/2500-2139-2018-11-2-192-197.[Kostroma II, Zhernyakova AA, Chubukina ZhV, et al. Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT. Clinical oncohematology. 2018;11(2):192–7. doi: 10.21320/2500-2139-2018-11-2-192-197. (In Russ)]

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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.

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Expression of Adhesion Molecule CD56 in Tumor Plasma Cells in Bone Marrow as a Prognostic Factor in Multiple Myeloma

LYMPHOID TUMORS , , , ,

MV Firsova, LP Mendeleeva, AM Kovrigina, MV Solov’ev, NL Deineko, MYu Drokov, VG Savchenko

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

For correspondence: Maiya Valer’evna Firsova, MD, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: firs-maia@yandex.ru

For citation: Firsova MV, Mendeleeva LP, Kovrigina AM, et al. Expression of Adhesion Molecule CD56 in Tumor Plasma Cells in Bone Marrow as a Prognostic Factor in Multiple Myeloma. Clinical oncohematology. 2019;12(4):377–84 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-377-384

ABSTRACT

Aim. To study immunohistochemical parameters of tumor plasma cells in bone marrow and to assess how the expression of adhesion molecule CD56 impacts overall survival (OS) of multiple myeloma (MM) patients.

Materials & Methods. The trial included 35 patients (19 men and 16 women) aged 23 to 73 years (with median age of 58 years) with newly diagnosed MM. At disease onset plasmacytoma was diagnosed in 21 patients. In all patients bone marrow core biopsy was performed followed by histologic and immunohistochemical (IHC) examinations. IHC examination was based on the panel of CD56, CD166, CXCR4, Ki-67, and c-MYC/CD138 antibodies. Kaplan-Meier survival curves and significance assessment by means of Cox’s F-Test were used.

Results. Expression mean values of most of studied markers (CD56, CXCR4, c-MYC, and Ki-67) in bone marrow of patients without plasmacytoma (n = 14) appeared to be higher than in patients with plasmacytoma at MM onset. Expression mean value is understood as percentage ratio of plasma cells expressing a studied marker to total cell count of tumor substrate. High expression of chemokine receptors (CXCR4), and adhesion molecules (CD56) probably inhibits plasma cell migration and impedes extramedullary tumor progression. Comparison of protein expression by tumor plasma cells in bone marrow in the groups with bone extramedullary plasmacytoma shows a distinct regularity referring to CD56 adhesion molecule. For example, CD56 expression is significantly (p < 0.05) lower in terms of the count of tumor plasma cells with marker expression in bone marrow of MM patients with extramedullary plasmacytoma compared with patients with bone plasmacytoma (1 ± 1 % vs. 65.71 ± 12.12 %). Comparison of MM patients’ OS depending on CD56 expression by tumor plasma cells in bone marrow showed that 4-year OS of patients with CD56 expression in bone marrow was significantly higher being 80 % vs. 38 % in the group with CD56 expression less than in 10 % of tumor cells.

Conclusion. Expression of adhesion molecule CD56 in tumor plasma cells in bone marrow can be regarded as a prognostic factor in MM. Probably, when at disease onset CD56 expression is identified in less than 10 % of tumor cells in bone marrow, more detailed additional examination of patients should be carried out to rule out extramedullary lesions in different organs and tissues.

Keywords: multiple myeloma, bone plasmacytoma, extramedullary plasmacytoma, bone marrow core biopsy, CD56.

Received: May 12, 2019

Accepted: September 2, 2019

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Experience with the Use of Thio/Mel Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

LYMPHOID TUMORS , , , ,

SV Gritsaev1, II Kostroma1, AA Zhernyakova1, IM Zapreeva1, EV Karyagina2, ZhV Chubukina1, SA Tiranova1, IS Martynkevich1, SS Bessmeltsev1, AV Chechetkin1

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: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Gritsaev SV, Kostroma II, Zhernyakova AA, et al. Experience with the Use of Thio/Mel Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma. Clinical oncohematology. 2019;12(3):282–8 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-282-288

ABSTRACT

Background. In multiple myeloma (MM) treatment a single autologous hematopoietic stem cell transplantation (auto-HSCT) is preceded by conditioning regimens aimed at intensifying cytoreductive effect. In the course of ongoing search for combined conditioning regimens an attractive option proved to be thiotepa/melphalan combination.

Aim. Data analysis of a pilot study of the efficacy of conditioning regimens including administration of two alkylating agents (thiotepa and melphalan) with subsequent auto-HSCT.

Materials & Methods. 9 patients received 10 auto-HSCTs with conditioning regimen including administration of 250 mg/m2 of thiotepa on Day –5 and 140 mg/m2 of melphalan on Day –2. After auto-HSCT pegylated filgrastim was administered in 8 patients. Engraftment period was calculated on the basis of absolute neutrophil count ≥ 0,5 × 109/L and thrombocyte level ≥ 20 × 109/L. Regimen toxicity was assessed according to CTCAE v5.0. Survival rates were estimated by Kaplan-Meier curves.

Results. The use of thiotepa did not require administration of any additional drugs. The incidence of mucositis and enteropathy of grade 1–2 was 100 % and 70 %, respectively. Pyrexia was reported in 7 auto-HSCTs. Pneumonia occurred in 1 patient. The infusion of 1–3 doses of platelet concentrate (median of 2 doses) was required in all patients except for one. Donor erythrocytes were transfused to 3 patients. Engraftment was reported in all patients within the period of 10–14 days. Median hospitalization duration from Day 0 to hospital discharge was 16 patient-days. After auto-HSCT the quality of response improved in 6 out of 9 patients. MM progression was reported in one patient with complex karyotype. Further follow-up showed progression in 2 patients. By December 2018 median follow-up of 9 patients from the date of auto-HSCT was 9 months (range 3–20 months), median progression-free survival was 17 months, median overall survival was not reached.

Conclusion. Acceptable toxicity, improvement of response quality, and maintenance of it for up to 20 months allow to consider combined conditioning regimen Thio/Mel to be a possible alternative to the standard Mel200 regimen.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, conditioning regimen, thiotepa, melphalan.

Received: December 26, 2018

Accepted: May 25, 2019

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Infectious Complications in Multiple Myeloma Patients Receiving Various Antitumor Regimens

ANTINEOPLASTIC THERAPY COMPLICATIONS , ,

AA Novikova, GA Klyasova, EO Gribanova, VV Ryzhko, TA Tupoleva, LP Mendeleeva, VG Savchenko

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

For correspondence: Anna Aleksandrovna Novikova, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(916)873-15-72; e-mail: annanovikova11@mail.ru

For citation: Novikova AA, Klyasova GA, Gribanova EO, et al. Infectious Complications in Multiple Myeloma Patients Receiving Various Antitumor Regimens. Clinical oncohematology. 2019;12(2):231–9.

DOI: 10.21320/2500-2139-2019-12-2-231-239

ABSTRACT

Aim. To study infectious complications and factors attributable to them as reported in multiple myeloma (MM) patients in the framework of state-of-the-art anticancer therapy.

Materials & Methods. The study included MM patients who received regimens based on bortezomib, lenalidomide, and bendamustine from January 2013 to August 2018. The regimens including thalidomide, melphalan, and aggressive antitumor treatment constituted the group of “others”.

Results. The study enrolled 174 patients (82 men and 92 women with median age of 61 years) with newly diagnosed MM (with median follow-up of 5.6 months). A total of 1362 courses of antitumor treatment were administered: 895 bortezomib (n = 174), 306 lenalidomide (n = 68), and 63 bendamustine (n = 22) regimens. The category of “others” included 98 treatment courses (n = 34). Infectious complications were reported in 129 (74.1 %) MM patients throughout the period of 344 (25.3 %) courses of antitumor treatment. Infection incidence on bortezomib (24.4 %), lenalidomide (20.3 %), and bendamustine (27 %) therapies was similar, and fell clearly below the infection incidence registered on the regimens constituting the group of “others” (48 %; р < 0.01). The most common infectious complications were pneumonias (54.9 %), urinary (24.7 %), and herpesviral infections (22.9 %). Herpesviral infections were predominantly associated with bortezomib treatment (29.8 %; p < 0.05). Significant factors (р < 0.05) associated with infection development were leukopenia, the presence of central venous catheter (CVC), need for blood transfusion, MM progression or relapse.

Conclusion. Infection incidence in MM patients receiving bortezomib, lenalidomide, and bendamustine anticancer therapy appeared to be similar, but considerably lower than in patients who received antitumor regimens belonging to category “others”. The prevalent type of infectious complications was pneumonia. Herpesviral infections were most common on bortezomib regimens. Factors related to infection development throughout all therapies were leukopenia, the presence of CVC, need for blood transfusion, MM progression or relapse.

Keywords: multiple myeloma, infectious complications, risk factors.

Received: January 26, 2019

Accepted: March 29, 2019

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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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Factors Associated with Efficient Harvesting and Engraftment of Auto-Transplants in Multiple Myeloma Patients

BONE MARROW TRANSPLANTATION , , , ,

II Kostroma, AA Zhernyakova, ZhV Chubukina, NYu Semenova, IM Zapreeva, SA Tiranova, SS Bessmeltsev, AV Chechetkin, SV Gritsaev

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

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Kostroma II, Zhernyakova AA, Chubukina ZhV, et al. Factors Associated with Efficient Harvesting and Engraftment of Auto-Transplants in Multiple Myeloma Patients. Clinical oncohematology. 2019;12(1):32–6.

DOI: 10.21320/2500-2139-2019-12-1-32-36

ABSTRACT

Background. The success of autologous hematopoietic stem cell transplantation (auto-HSCT) depends on the speed of transplant engraftment which in turn is affected by the count of harvested and infused hematopoietic stem cells (HSC).

Aim. To identify predictors of auto-HSCT efficacy in multiple myeloma (MM) patients under introduction of new drugs at the phase of HSC induction and mobilization.

Materials & Methods. The results of auto-transplant harvesting and engraftment were retrospectively analyzed in 75 MM patients during 112 auto-HSCTs. Auto-transplants were harvested using cyclophosphamide and vinorelbine combined with granulocyte colony-stimulating factor (G-CSF) without plerixafor. Conditioning regimen included melphalan 200 mg/m2 or 140 mg/m2, and combination of tiothepa with melphalan. All patients received subcutaneous injections of G-CSF in post-transplantation period. Transplant engraftment was assessed according to absolute neutrophil count of ≥ 0.5 × 109/L, and thrombocyte count of ≥ 20 × 109/L.

Results. It is established that the predictors of a high CD34+ cell count in auto-transplant are a single previous induction regimen (p = 0.0315) and administration of cyclophosphamide in mobilization regimen (р = 0.0001). Transplant engraftment period is determined by auto-HSCT serial number and amount of infused CD34+ cells. Hematopoiesis regeneration after the second auto-HSCT was accelerated by more frequent use of Mel140 (р = 0.001).

Conclusion. Auto-transplant quality and engraftment period in MM patients primarily depend on the efficacy of induction therapy and the intensity of HSC mobilization regimen. Therefore, induction therapy and mobilization regimen need to be tailored to an individual patient, MM prognostic variant, probability of response to standard induction regimens, and the number of planned auto-HSCTs.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, auto-HSCT efficacy predictors, transplant, engraftment.

Received: May 14, 2018

Accepted: December 2, 2018

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Practical Aspects of the Use of Carfilzomib in Multiple Myeloma

NOVEL DRUGS , , , , ,

SV Semochkin1,2, GN Salogub3, SS Bessmeltsev4, KD Kaplanov5

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

2 Municipal Clinical Hospital No. 52, 3 Pekhotnaya str., Moscow, Russian Federation, 123182

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

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

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

For correspondence: Prof. Sergei Vyacheslavovich Semochkin, MD, PhD, 3 Pekhotnaya str., Moscow, Russian Federation, 123182; Tel./fax: +7(495)369-00-36; e-mail: semochkin_sv@rsmu.ru

For citation: 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

ABSTRACT

Carfilzomib (Kyprolis®, Amgen), a second-generation proteasome inhibitor, is capable of covalent bonding and irreversible inhibition of the 20S proteasome chymotrypsin-like activity. In 2016 this drug was approved in Russia for monotherapy of relapsed refractory multiple myeloma (MM) and in combination with lenalidomide and dexamethasone (KRd) or only with dexamethasone (Kd) for treatment of patients with relapsed MM after at least one line of prior therapy. The present review outlines mechanism, clinical efficacy, and adverse effects of carfilzomib according to the data of a phase II (monotherapy) trial and two key randomized phase III (carfilzomib combined with other drugs) trials. The ASPIRE trial demonstrated that adding carfilzomib to the combination of lenalidomide and dexamethasone (KRd) significantly improves progression-free survival (PFS) compared with the Rd original regimen (median 26.3 vs. 17.6 months; hazard ratio [HR] 0.69; p = 0.0001). Median overall survival (OS) was 48.3 months (95% confidence interval [95% CI] 42.4–52.8 months) for KRd vs. 40.4 months (95% CI 33.6–44.4 months) for Rd (HR 0.79; p = 0.0045). The ENDEAVOR trial showed that as compared with combination of bortezomib and dexamethasone (Vd) the carfilzomib + dexamethasone (Kd) regimen significantly improves PFS (median 18.7 vs. 9.4 months; HR 0.53; p < 0.0001) and OS (47.6 vs. 40.0 months; HR 0.79; p = 0.010) as well. The present review also discusses how carfilzomib is to be used in special patient groups (with renal failure and high cytogenetic risk).

Keywords: carfilzomib, proteasome inhibitor, lenalidomide, bortezomib, multiple myeloma, renal failure, cytogenetic risk.

Received: May 12, 2018

Accepted: December 28, 2018

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