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

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

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)

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

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    [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)]

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

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

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; = 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; = 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; < 0.0001) and OS (47.6 vs. 40.0 months; HR 0.79; = 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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Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT

VA Balashova, VI Rugal’, SS Bessmel’tsev, SV Gritsaev, NYu Semenova, SV Voloshin, ZhV Chubukina, AV Shmidt, AD Garifullin, IM Zapreeva, AA Kuzyaeva, II Kostroma, AYu Kuvshinov, AV Chechetkin

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

For correspondence: Valentina Andreevna Balashova, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-19-37; e-mail: vbspb37@mail.ru

For citation: Balashova VA, Rugal’ VI, Bessmel’tsev SS, et al. Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT. Clinical oncohematology. 2018;11(4):368–77.

DOI: 10.21320/2500-2139-2018-11-4-368-377


ABSTRACT

Aim. To establish correlation between CD34+ autologous hematopoietic stem cell (HSC) count and colony-forming units (CFU) in the same peripheral blood apheresis product samples before and after cryopreservation in multiple myeloma and lymphoma patients, and to assess clinical value of these parameters.

Materials & Methods. Cell samples of peripheral blood cytapheresis product and cell cultures were studied before and after cryopreservation in 32 multiple myeloma and 25 lymphoma patients who underwent autologous HSC transplantation. The material was analyzed using culture technique and flow cytometry.

Results. The paper provides information on the relationship between CD34+ HSC count obtained by flow cytometry, and CFU in cell culture obtained by cytapheresis of the same peripheral blood samples. A direct correlation was confirmed between CD34+ count and all the CFUs before and after cryopreservation in lymphoma patients. Correlation between CD34+ count and granulocyte-macrophage CFUs was revealed in multiple myeloma and lymphoma patients before cryopreservation.

Conclusion. The parameter of colony-forming capacity used for the assessment of the functional HSC was shown to be equally reliable criterion for condition evaluation of autotransplant proliferative pool than CD34+ cells. Both methods should be applied for qualitative and quantitative evaluation of an autotransplant for multiple myeloma and lymphoma patients.

Keywords: CD34+ cells, CFU, CFU-GM, correlation, lymphoma, multiple myeloma, apheresis, auto-HSCT.

Received: April 11, 2018

Accepted: July 28, 2018

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Magnetic Resonance Imaging of Bone Marrow and its Results as a Criterion for Administration of Maintenance Therapy After Auto-HSCT in Multiple Myeloma Patients

MV Solov’ev, LP Mendeleeva, GA Yatsyk, NS Lutsik, MV Firsova, EG Gemdzhian, VG Savchenko

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

For correspondence: Maksim Valer’evich Solov’ev, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-31-92; е-mail: maxsolovej@mail.ru

For citation: Solov’ev MV, Mendeleeva LP, Yatsyk GA, et al. Magnetic Resonance Imaging of Bone Marrow and its Results as a Criterion for Administration of Maintenance Therapy After Auto-HSCT in Multiple Myeloma Patients. Clinical oncohematology. 2018;11(4):360–7.

DOI: 10.21320/2500-2139-2018-11-4-360-367


ABSTRACT

Aim. To evaluate the efficacy of maintenance therapy in multiple myeloma (MM) patients after autologous hematopoietic stem cell transplantation (auto-HSCT) based on the results of MRI of bone marrow.

Materials & Methods. The study included 32 MM patients aged 36 to 66 years (median 57 years) with complete remission after a single auto-HSCT. MRI of spine and pelvic bones was performed to identify the nature of bone marrow lesions and to determine the volume of tumor tissue on the day 100 after auto-HSCT. As maintenance therapy after auto-HSCT 14 patients received daily 15 mg lenalidomide in the period from day 1 to day 21 of the 28-day treatment course within 1 year. Monitoring of 18 patients was conducted without maintenance therapy. Statistical analysis included the assessment of progression-free survival (PFS) and relapse risk relationship to clinical and laboratory parameters.

Results. Twenty patients had a positive MRI (tumor volume > 1 cm3). Zero variation of MR signal in bone marrow and detection of a < 1 cm3 tumor were regarded as a negative MRI, which was the case in 12 patients. After reaching the negative MRI the best rates of 2-year PFS were registered: 100 % with maintenance therapy and 84 % without maintenance therapy. In patients with tumor load on MR scans the 2-year PFS significantly (= 0.03) varied and accounted for 80 % in patients who received maintenance therapy vs. 33 % in patients without maintenance therapy. Administration of maintenance therapy after detecting residual tumor on MR scans on day 100 after auto-HSCT has a positive effect on PFS rates. Multivariate analysis confirmed the residual tumor on MR scans of bone marrow to be the most important parameter PFS depends on.

Conclusion. A negative MRI after auto-HSCT is a favourable prognostic factor determining a long-lasting (> 2 years) MM free period, despite the lack of maintenance therapy.

Keywords: multiple myeloma, magnetic resonance imaging (MRI), autologous hematopoietic stem cell transplantation (auto-HSCT), maintenance therapy, minimal residual disease.

Received: May 11, 2018

Accepted: August 29, 2018

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REFERENCES

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The Use of Pomalidomide in the Treatment of Relapsed/Refractory Multiple Myeloma in Patients with Renal Failure

IG Rekhtina, MV Nareiko, LP Mendeleeva

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

For correspondence: Irina Germanovna Rekhtina, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-49-66; e-mail: rekhtina.i@blood.ru

For correspondence: Rekhtina IG, Nareiko MV, Mendeleeva LP. The Use of Pomalidomide in the Treatment of Relapsed/Refractory Multiple Myeloma in Patients with Renal Failure. Clinical oncohematology. 2018;11(4):283–7.

DOI: 10.21320/2500-2139-2018-11-4-283-287


ABSTRACT

The present review includes data on efficacy and safety of pomalidomide, an immunomodulating 3rd generation drug used for treatment of relapsed and refractory multiple myeloma patients with renal failure. The results of multicenter randomized trials proved similar efficacy and comparable safety profile in patients with normal renal function and patients with moderate and/or severe renal failure. All patients received the standard starting dose. Pomalidomide dose needs to be reduced in response to hematological toxicity. The paper provides practical guidelines on the use of pomalidomide and treatment of adverse events adopted by consensus of international experts. Current approaches to multiple myeloma with renal failure, and the use of pomalidomide in particular, are demonstrated by means of a clinical case.

Keywords: multiple myeloma, pomalidomide, renal failure.

Received: March 28, 2018

Accepted: July 16, 2018

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REFERENCES

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    [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)]

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Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT

II Kostroma, AA Zhernyakova, ZhV Chubukina, IM Zapreeva, SA Tiranova, AV Sel’tser, NYu Semenova, SS Bessmel’tsev, 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; Теl.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: 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


ABSTRACT

Background. A prompt graft acceptance is essential for positive autologous hematopoietic stem cell transplantation (auto-HSCT) outcome in multiple myeloma patients (MM). Prompt and favourable hematopoietic regeneration is associated with CD34+ cell count in a transplant. Although the indicators of low autotransplant cellularity have been defined, the practical application of new drug products and HSC mobilization regimens strengthens the relevance of determining their influence on the transplant quality.

Aim. To determine the factors that are associated with low efficacy of auto-HSCT in MM patients and to evaluate the impact of lenalidomide during induction period and of vinorelbine as a mobilization regimen on the prognosis.

Materials & Methods. The authors performed a retrospective analysis of autotransplant collection results in 68 MM patients treated with two mobilization regimens: 3 g/m2 cyclophosphamide with granulocyte colony-stimulating factor (G-CSF) and 30 mg/m2 vinorelbine with G-CSF. Mobilization was aimed at collecting not less than 2–4 × 106 CD34+ cells per kg body mass. CD34+ cell count was determined by four-color analysis on the Cytomics FC 500 laser flow cytometer.

Results. The analysis showed that age or MM immunochemical specificity were not associated with CD34+ cell count in the transplant. Prior lenalidomide treatment compared to therapy without immunomodulators (4.1 × 106/kg vs. 7.76 × 106/kg) tends to decrease CD34+ count (р = 0.066). Cyclophosphamide included into mobilization regimen compared to vinorelbine (3.96 × 106/kg vs. 6.8 × 106/kg) significantly increased CD34+ cell count (р = 0.022).

Conclusion. The decrease of CD34+ cell count in the autotransplant of the MM patients treated with lenalidomide prior to auto-HSC collection, and a lower mobilization activity of vinorelbine provide a basis for a differentiated selection of mobilization regimens. Vinorelbine may be administered to patients with a single auto-HSCT, i.e. elderly people and patients with complete response. In case of substantial lenalidomide treatment prior to auto-HSCT, intermediate-dose cyclophosphamide is preferred.

Keywords: auto-HSCT, multiple myeloma, mobilization regimen, cyclophosphamide, vinorelbine, lenalidomide, predictors.

Received: November 29, 2017

Accepted: February 9, 2018

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Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of New Drugs

OV Pirogova, EI Darskaya, VV Porunova, OV Kudyasheva, AG Smirnova, IS Moiseev, EV Babenko, BV Afanas’ev

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Ol’ga Vladislavovna Pirogova, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; e-mail: dr.pirogova@gmail.com.

For citation: Pirogova OV, Darskaya EI, Porunova VV, et al. Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of New Drugs. Clinical oncohematology. 2018;11(2):187–91.

DOI: 10.21320/2500-2139-2018-11-2-187-191


ABSTRACT

Background & Aims. The present retrospective single-center study analysed the impact of high-dose chemotherapy with melphalan with subsequent autologous hematopoietic stem cell transplantation (auto-HSCT) on survival in multiple myeloma (MM) in the era of new induction regimens.

Materials & Methods. The clinical trial included 133 MM patients aged from 31.2 to 78.2 years (the median age was 55.3 years). There were 66 female and 67 male patients. Bortezomib-based regimens as first-line treatment were administered in 133 MM patients, 74 of them received high-dose chemotherapy with melphalan and either single (n = 25), or double (n = 49) auto-HSCT as consolidation therapy in the period from 2006 to 2016.

Results. The overall 5-year survival (OS) rates were 86.5 % for the auto-HSCT treated group vs. 72.9 % for the non-auto-HSCT treated group (= 0.03); 5-year progression-free survival (PFS) rates were 64.9 vs. 39 % for the auto-HSCT and non-auto-HSCT treated groups, respectively (= 0.0016). MM relapse/progression occurred more frequently in the non-auto-HSCT treated patients (52.5 vs. 28.4 %; = 0.0016). In multivariate analysis the age above 60 was determined as prognostic factor of lower PFS and increase in relapse/progression rate (= 0.004 and = 0.04, respectively). The variant of monoclonal protein (Bence-Jones myeloma) was determined as prognostic factor of higher OS and decrease in relapse/progression rate (= 0.02 and = 0.04, respectively). Complete nonresponsiveness to induction therapy has proved to be an independent predictor of both poor OS and PFS (= 0.04 and = 0.041, respectively). 2-year bortezomib-based maintenance therapy following the auto-HSCT treatment resulted in a statistically significant improvement in 5-year PFS (67.4 vs. 60.7 %; = 0.03) and a decrease in relapse/progression frequency (26.1 vs. 32.1 %; = 0.05).

Conclusion. High-dose chemotherapy with melphalan with subsequent auto-HSCT is an effective MM treatment strategy, and a subsequent long-term maintenance therapy results in a PFS improvement and a decrease in relapse/progression frequency.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, maintenance therapy.

Received: November 20, 2017

Accepted: February 9, 2018

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