scholarly journals Successful Stem Cell Mobilization and Autologous Stem Cell Transplantation after Pretreatment Consisting of Bendamustine, Prednisone and Bortezomib (BPV) in 35 Patients with Newly Diagnosed/Untreated Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5900-5900
Author(s):  
Wolfram Poenisch ◽  
Madlen Ploetze ◽  
Bruno Holzvogt ◽  
Marc Andrea ◽  
Thomas Zehrfeld ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Research Funding ◽  
Median Number ◽  
Stem Cell Mobilization ◽  
Newly Diagnosed ◽  
Cell Mobilization

Abstract Introduction: Bendamustine is a bifunctional alkylating agent with low toxicity that produces both single- and double-strand breaks in DNA, and shows only partial cross resistance with other alkylating drugs. Treatment of patients with newly diagnosed multiple myeloma using Bendamustine and Prednisone in comparison to Melphalan and Prednisone results in superior complete response rate and prolonged time to treatment failure (Poenisch et al, Res Clin Oncol 132: 205-212;2006). So far, however, reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell transplantation (SCT) after induction treatment with a combination of bendamustine, prednisone and bortezomib (BPV) is missing. Material and Methods: A retrospective analysis of peripheral blood stem cell mobilization and autologous SCT was performed in 35 patients with multiple myeloma who had received at least two cycles of a BPV induction therapy consisting of bendamustine 60 mg/m2 on days 1 and 2, bortezomib 1.3 mg/m² on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11 between October 2008 and May 2014. The mobilization regimen consisted of cyclophosphamide 4 g/m2 and G-CSF (2x5µg/kg). Apheresis was started as soon as peripheral blood CD34+ counts exceeded 20x106/l with a harvest target of 8x106 CD34+/kg. The minimal accepted target was 2x106 CD34+/kg. Results: A median number of two (range 1–5) BPV treatment cycles were given to the patients. The majority of the patients (n = 31, 89 %) responded including 2 sCR, 5 nCR, 11 VGPR, and 13 PR. Three patients had MR, and 1 SD. Stem cell mobilization and harvest was successful in all patients. In 19 of 35 patients (54 %) a single apheresis was sufficient to reach the target. The median number of aphereses was one (range 1-4) and the median CD34+ cell-count/kg was 13.5 (range 3.2-33.1) x106. All patients received an autologous SCT. The pre-transplantation conditioning therapy consisted of melphalan 200 mg/m2. In 8 patients with concomitant heart amyloidosis or severe renal insufficiency melphalan dose was reduced to 100 or 140 mg/m2. Engraftment was successful in 34 of 35 patients. The median time to leucocytes count >l×109/l was reached after 11 (range 9–18) days and the time to untransfused platelet count of >50×109/l was 13 (range 10–55) days. 34 patients (97%) responded after the autologous SCT with 11 sCR, 2 CR, 7 nCR, 7 VGPR, and 7 PR. The progression free survival at 18 months was 87 % and overall survival was 92 %. Conclusion: Stem cell mobilization and autologous SCT is feasible in multiple myeloma patients who have received BPV induction therapy. Disclosures Al-Ali: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Lange:Novartis: Consultancy, Honoraria, Research Funding.

Impact of Bendamustine Pretreatment on Stem Cell Mobilization and Autologous Stem Cell Transplantation in Patients with Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1933-1933 ◽  
Author(s):  
Wolfram Pönisch ◽  
Julia Wiesler ◽  
Ina Wagner ◽  
Sabine Leiblein ◽  
Elvira Edel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Research Funding ◽  
Stem Cell Mobilization ◽  
Cross Resistance ◽  
Cell Mobilization

Abstract Abstract 1933 Introduction: Bendamustine is a bifunctional alkylating agent with low toxicity that produces both single- and double-strand breaks in DNA, and shows only partial cross resistance with other alkylating drugs. Treatment of patients with newly diagnosed multiple myeloma using Bendamustine and Prednisone in comparison to Melphalan and Prednisone results in superior complete response rate and prolonged time to treatment failure (Poenisch et al, Res Clin Oncol 132: 205–212;2006). So far, however, reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell transplantation (SCT) after Bendamustine therapy is missing. Material and Methods: A retrospective analysis of peripheral blood stem cell mobilization and autologous SCT was performed in 63 patients with multiple myeloma who had received Bendamustine pretreatment at the university Hospitals Leipzig and Heidelberg over a period of sixteen years. Patients had a median age of 59 (range, 31–72) years. The cumulative dosis of Bendamustine per patient ranged between 120 and 2400mg/qm and was administered during a median of three (range 1–10) cycles. The mobilization regimen consisted of Cyclophosphamide 4g/qm (n=41) or 7g/qm (n=4) and G-CSF (2×5ug/kg). Alternative regimens such as CAD, CED, TCED and others were also used in the remaining patients. Apheresis was started as soon as peripheral blood CD34+ counts exceeded 10×106/l with a harvest target of 4×106 CD34+/kg using 4 times the blood volume. The minimal accepted target was 2×106 CD34+/kg. Results: Stem cell mobilization and harvest was successful in 60 of the 63 patients (95 %). In 19 of 60 patients (32 %) a single apharesis was sufficient to reach the target. The median number of aphareses was two (range 1–7) and the median CD34+ cell-count/kg was 5.9 (range 1.7–20.4) x106. Information on autologous SCT is available from all 60 patients with successful harvest. Engraftment was successful in 59 of 60 patients. The median time to leucocytes count > l ×109/l was reached after 12 days and the time to untransfused platelet count of >50×109/l was 14 days. 54 patients (90%) responded after the autologous SCT with 6 CR, 4 nCR, 12 VGPR, and 32 PR. The event free survival at 36 months was 31 % and overall survival was 68 %. In conclusion, the stem cell mobilization and autologous SCT is feasible in multiple myeloma patients who have received Bendamustine pretreatment. Disclosures: Pönisch: Mundipharma: Honoraria, Research Funding. Niederwieser:Mundipharma: Research Funding.

Timing of Daratumumab Administered Pre-Mobilization in Multiple Myeloma Impacts Pre-Harvest Peripheral Blood CD34+ Cell Counts and Plerixafor Use

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Danny Luan ◽  
Paul J Christos ◽  
Michael Ancharski ◽  
Danielle Guarneri ◽  
Roger Pearse ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Research Funding ◽  
Stem Cell Mobilization ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Peripheral Blood Cd34 ◽  
Hematopoietic Recovery ◽  
Cell Mobilization

Background: Daratumumab (DARA) is a monoclonal antibody which targets CD38 on plasma cells and B cell progenitors. DARA has been effectively combined with other therapies in newly diagnosed and relapsed/refractory multiple myeloma (RRMM), while DARA-based induction regimens in transplant-eligible patients (pts) are increasingly being used in clinical practice. Given that hematopoietic stem cells also express CD38, DARA may potentially affect stem cell mobilization and hematopoietic reconstitution following autologous stem cell transplant (ASCT). Although no clinically significant impact of DARA on stem cell mobilization or hematopoietic recovery was described in large phase 3 trials of triplet induction regimens +/- DARA in newly diagnosed MM, stem cell yields were lower and plerixafor more commonly used in the DARA-containing arms [Moreau et al, Lancet 2019; Voorhees et al, Blood 2020]. Significantly longer time to neutrophil (PMN) engraftment was also reported in pts receiving DARA-based induction who underwent upfront ASCT [Al Saleh et al, Am J Hematol 2020]. In this study, we examine the impact of timing of DARA administration pre-mobilization on day 4 pre-harvest peripheral blood CD34 cell count, stem cell apheresis yield, and post-ASCT engraftment. Methods: Between 1/1/2016 and 12/31/2019, newly diagnosed and RRMM pts receiving DARA-based induction regimens with ≥1 dose of DARA administered within 1 month prior to stem cell mobilization were identified retrospectively and compared to matched controls receiving similar induction regimens without DARA. Granulocyte colony-stimulating factor (G-CSF) was administered per institutional standards and plerixafor added based on day 4 pre-harvest peripheral blood CD34 counts. PMN and platelet engraftment post-ASCT was defined as the first of 3 consecutive days with sustained PMN count >500 x 106/L and independence from platelet transfusion in the preceding 7 days with a count >20 x 109/L, respectively. Pre-harvest peripheral blood CD34 counts and stem cell apheresis yields were obtained from the Cellular Therapy Laboratory at NewYork-Presbyterian Hospital. The study was approved by the Weill Cornell Medicine IRB. Results: We identified 16 pts who received DARA-based induction with ≥1 dose of DARA administered within 1 month of apheresis (DARA group) and 16 non-DARA-containing regimen-matched controls (non-DARA group). Demographics of the DARA and non-DARA groups were well matched (Table 1). DARA pts received their last dose of DARA a mean of 17.3 days prior to the first day of apheresis, with 8 pts receiving their last dose within 2 weeks and the remaining 8 pts between 2 weeks and 1 month prior. Overall, mobilization outcomes were inferior in the DARA group (Table 2). DARA pts had significantly lower day 4 pre-harvest peripheral blood CD34 counts compared to non-DARA pts (17.2 vs 35.4 cells/µL; P=0.0146). Institutional algorithm required plerixafor to be given for day 4 CD34 count ≤40 cells/µL. Fifteen of the 16 DARA pts received plerixafor vs. 11 non-DARA pts (P=0.07). Additionally, DARA pts required significantly more apheresis days (2.4 vs 1.6 days; P=0.0279). Differences in stem cell yield were not significant (8 vs 10 x106cells/kg; P=0.1391). Hematopoietic recovery post-ASCT was not affected by DARA administered in the month preceding mobilization. Conclusions: In summary, we report lower day 4 pre-harvest peripheral blood CD34 count, increased requirement for plerixafor, and longer apheresis duration in newly diagnosed and RRMM pts receiving DARA within 1 month ofstem cell mobilization. These limitations are largely overcome by plerixafor usage which, combined with G-CSF, resulted in successful stem cell collection in all patients. Limitations in our study include small sample sizes, retrospective control selection, and fewer pts in the DARA group achieving ≥VGPR prior to mobilization. Nevertheless, our findings are consistent with inferior mobilization outcomes reported in the DARA-containing arms of phase 3 trials of triplet induction +/- DARA and highlight the nearly universal requirement for plerixafor usage when DARA is administered within a month prior to apheresis. Prospective study of day 4 pre-harvest peripheral blood CD34 counts and other predictors of stem cell yield should be incorporated into future clinical trials of CD38 monoclonal antibody-based induction regimens for transplant-eligible MM pts. Disclosures Rossi: Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Niesvizky:GSK: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Rosenbaum:Amgen: Research Funding; GlaxoSmithKline: Research Funding; Akcea: Honoraria; Celgene: Honoraria; Janssen: Research Funding.

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