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.

Successful Mobilization of Peripheral Blood Stem Cells After Intensive Bendamustine Pre-Treatment In Patients with Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4439-4439
Author(s):  
Wolfram Pönisch ◽  
Julia Wiesler ◽  
Sabine Leiblein ◽  
Elvira Edel ◽  
Haifa K. Al-Ali ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Research Funding ◽  
Median Number ◽  
Advisory Committees ◽  
Peripheral Blood Cd34 ◽  
Ortho Biotech ◽  
Cell Mobilization

Abstract Abstract 4439 Introduction The alkylating agent bendamustine has structural similarities to both alkylating agents and purine analogs, and is effective in the treatment of patients with multiple myeloma. So far, no data are available on stem cell toxicity or on stem cell mobilization. Since autologous stem cell transplantation is an established treatment for multiple myeloma after primary treatment, we were interested in analysing the experience of stem cell mobilization after bendamustine treatment. Material and Methods A retrospective analysis over a period of fifteen years was carried out in 56 (34 male and 22 female) patients with multiple myeloma after bendamustine pretreatment at the university hospitals Leipzig and Heidelberg. Patients had a median age of 58 (range 31–72) years. The median number of cycles was 3 (range 1–10) and the cumulative bendamustine dose ranged from 120 to 2400 mg/qm. The mobilization regimen in 37 cases was either cyclophosphamide 4 g/qm (n=33) or 7 g/qm (n=4) followed by G-CSF (2×5 ug/kg s.c.). Alternative regimens such as CAD, CED, TCED and others were used for mobilization in the remaining 19 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 harvest was successful in 54 of the 56 patients. In one patient the peripheral blood CD34+ cell count failed to reach 10 × 106/l and no apheresis was performed. In one further patient a rapid decrease in peripheral blood CD34+ counts resulted in insufficient recovery of stem cells in the apheresis product. In 18 out of 54 patients (33%) the target was reached with a single apharesis. The median number of aphareses in the 54 patients was 2 (range 1–7) and the median CD34+ cell-count obtained was 5.5 (range 1.7–20.4) × 106/kg. Engraftment was successful in 52/53 patients receiving a stem cell transplant. One patient was successfully harvested and did not receive the transplant yet. Conclusion From this retrospective analysis we conclude that mobilization of PBSC is possible after intensive bendamustine pretreatment. Disclosures: Niederwieser: Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau. Goldschmidt:Celgene: Membership on an entity's Board of Directors or advisory committees; Ortho Biotech: Membership on an entity's Board of Directors or advisory committees; Ortho Biotech: Research Funding; Celgene: Research Funding; Chugai Pharma: Research Funding; Amgen: Research Funding.

scholarly journals Lower Hematopoietic Progenitor Cell Counts and Yields at Subsequent Donations Is Influenced By a Shorter Inter-Donation Interval between the First and Subsequent Mobilizations

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1962-1962
Author(s):  
Sandhya R. Panch ◽  
Brent R. Logan ◽  
Jennifer A. Sees ◽  
Bipin N. Savani ◽  
Nirali N. Shah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Research Funding ◽  
Time Interval ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Peripheral Blood Cd34 ◽  
Cell Counts ◽  
Cd34 Cells

Introduction: Approximately 7% of unrelated hematopoietic stem cell (HSC) donors are asked to donate a subsequent time to the same or different recipient. In a recent large CIBMTR study of second time donors, Stroncek et al. incidentally found that second peripheral blood stem cell (PBSC) collections had lower total CD34+ cells, CD34+ cells per liter of whole blood processed, and CD34+ cells per kg donor weight. Based on smaller studies, the time between the two independent PBSC donations (inter-donation interval) as well as donor sex, race and baseline lymphocyte counts appear to influence CD34+ cell yields at subsequent donations. Our objective was to retrospectively evaluate factors contributory to CD34+ cell yields at subsequent PBSC donation amongst NMDP donors. Methods. The study population consisted of filgrastim (G-CSF) mobilized PBSC donors through the NMDP/CIBMTR between 2006 and 2017, with a subsequent donation of the same product. evaluated the impact of inter-donation interval, donor demographics (age, BMI, race, sex, G-CSF dose, year of procedure, need for central line) and changes in complete blood counts (CBC), on the CD34+ cell yields/liter (x106/L) of blood processed at second donation and pre-apheresis (Day 5) peripheral blood CD34+ cell counts/liter (x106/L) at second donation. Linear regression was used to model log cell yields as a function of donor and collection related variables, time between donations, and changes in baseline values from first to second donation. Stepwise model building, along with interactions among significant variables were assessed. The Pearson chi-square test or the Kruskal-Wallis test compared discrete variables or continuous variables, respectively. For multivariate analysis, a significance level of 0.01 was used due to the large number of variables considered. Results: Among 513 PBSC donors who subsequently donated a second PBSC product, clinically relevant decreases in values at the second donation were observed in pre-apheresis CD34+ cells (73.9 vs. 68.6; p=0.03), CD34+cells/L blood processed (32.2 vs. 30.1; p=0.06), and total final CD34+ cell count (x106) (608 vs. 556; p=0.02). Median time interval between first and second PBSC donations was 11.7 months (range: 0.3-128.1). Using the median pre-apheresis peripheral blood CD34+ cell counts from donation 1 as the cut-off for high versus low mobilizers, we found that individuals who were likely to be high or low mobilizers at first donation were also likely to be high or low mobilizers at second donation, respectively (Table 1). This was independent of the inter-donation interval. In multivariate analyses, those with an inter-donation interval of >12 months, demonstrated higher CD34+cells/L blood processed compared to donors donating within a year (mean ratio 1.15, p<0.0001). Change in donor BMI was also a predictor for PBSC yields. If donor BMI decreased at second donation, so did the CD34+cells/L blood processed (0.74, p <0.0001). An average G-CSF dose above 960mcg was also associated with an increase in CD34+cells/L blood processed compared to donors who received less than 960mcg (1.04, p=0.005). (Table 2A). Pre-apheresis peripheral blood CD34+ cells on Day 5 of second donation were also affected by the inter-donation interval, with higher cell counts associated with a longer time interval (>12 months) between donations (1.23, p<0.0001). Further, independent of the inter-donation interval, GCSF doses greater than 960mcg per day associated with higher pre-apheresis CD34+ cells at second donation (1.26, p<0.0001); as was a higher baseline WBC count (>6.9) (1.3, p<0.0001) (Table 2B). Conclusions: In this large retrospective study of second time unrelated PBSC donors, a longer inter-donation interval was confirmed to be associated with better PBSC mobilization and collection. Given hematopoietic stem cell cycling times of 9-12 months in humans, where possible, repeat donors may be chosen based on these intervals to optimize PBSC yields. Changes in BMI are also to be considered while recruiting repeat donors. Some of these parameters may be improved marginally by increasing G-CSF dose within permissible limits. In most instances, however, sub-optimal mobilizers at first donation appear to donate suboptimal numbers of HSC at their subsequent donation. Disclosures Pulsipher: CSL Behring: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Research Funding; Bellicum: Consultancy; Amgen: Other: Lecture; Jazz: Other: Education for employees; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Medac: Honoraria. Shaw:Therakos: Other: Speaker Engagement.

Peripheral Blood Stem Cell Collection In Patients Undergoing Induction Therapy with Lenalidomide Based Regimens: Failure Rates and Salvage Approaches

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2253-2253
Author(s):  
Shirshendu Sinha ◽  
Morie Gertz ◽  
Martha Lacy ◽  
Angela Dispenzieri ◽  
Suzanne Hayman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Research Funding ◽  
Colony Stimulating Factor ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Stimulating Factor ◽  
Stem Cell Collection

Abstract Abstract 2253 Background: Lenalidomide based combinations are among the most common initial therapies for myeloma. Previous studies have suggested that lenalidomide therapy can result in suboptimal stem cell collection in patients eligible to undergo autologous stem cell transplantation, especially older patients after prolonged exposure to the drug. Many salvage approaches are used when attempting repeat stem cell collection in this patient group. Patients and Methods: Two hundred twenty four patients who underwent stem cell collection following lenalidomide-dexamethasone induction from July 2004 and December 2009 were included in the current analysis. Data pertaining to the duration of lenalidomide therapy, stem cell mobilization regimen, and the collection yields were collected from the medical records. Results: The median age at mobilization was 60.6 years (range; 29, 76) and 136 (60%) were male. There were a total of 245 collection attempts from among 224 patients, 21 (9.8%) patients attempting to remobilize after failing to collect the desired numbers of stem cells at the first attempt. We first analyzed the results of the initial collection attempt. The median duration of lenalidomide therapy prior to stem cell collection was 4 months (range; 1, 26). The mobilization strategies were GCSF (Granulocyte Colony Stimulating Factor) alone in 151 (67%) patients, cyclophosphamide (CTX) followed by GCSF in 29 (13%) patients, and GCSF plus AMD3100 in 44 (20%) patients. Among those receiving AMD3100, it was added either due to peripheral blood CD34 cell count not reaching the threshold for initiation of harvest or for poor first day CD34 cells collection in 34 patients and given in a planned fashion in 10 patients. Overall 15 patients (7%) failed to reach the peripheral CD34 cell counts required to initiate apheresis, and among those starting apheresis 6 patients failed to collect at least 2 million CD34 cells/kg; a cumulative failure rate of 9%. Another 18 (8%) patients failed to collect at least 4 million CD34 cells /kg. The CD34 cells yield on day 1, the total yield, number of collections, the average daily yield and the percentage of the targeted cells collected for each mobilization strategy including failure rates are detailed in the table. Twenty-one patients reattempted stem cell mobilization; including 14 that failed a first attempt and 7 did who not achieve the intended goal even though they collected more than 2 million CD34 cells/kg. The mobilization regimens were GCSF alone, CTX + GCSF, GCSF + GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) and GCSF + AMD in 5, 8, 3, and 4 patients respectively. All patients collected at least 2 million CD34 cells /kg and 14 patients (70%) collected more than 4 million CD34 cells /kg. The median CD34 cells collected with the second attempt was 5.4 million/kg (rang; 2, 19.5) bringing the median total collection for these 21 patients to 9.6 million/kg (2.6-19.6). Overall, of the 224 patients studied, all but the 6 patients who failed initially and did not attempt a second collection collected at least 2 million CD34 cells /kg and 197 (88%) collected at least 4 million CD34 cells/kg. Conclusion: While the overall failure rate of stem cell collection in patients receiving initial therapy with lenalidomide is 10%, a risk adapted approach of adding AMD3100 appear to decrease the risk of failure. However, majority of patients failing a stem cell harvest attempt can be salvaged with a second collection allowing these patients to proceed to a stem cell transplant if desired. Disclosures: Gertz: Celgene: Honoraria; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genzyme: Research Funding. Lacy: Celgene: Research Funding. Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Micallef: Genzyme: Membership on an entity's Board of Directors or advisory committees. Kumar: Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

scholarly journals Evaluation of Stem Cell Mobilization in Patients with Multiple Myeloma after Lenalidomide-Based Induction Chemotherapy within the GMMG-HD6 Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3373-3373 ◽  
Author(s):  
Patrick Wuchter ◽  
Uta Bertsch ◽  
Hans-Juergen Salwender ◽  
Markus Munder ◽  
Mathias Haenel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Research Funding ◽  
Stem Cell Mobilization ◽  
Phase Iii ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Introduction: The German-Speaking Myeloma Multicenter Group (GMMG) has initiated a randomized multicenter phase III trial on the effect of elotuzumab in VRD (bortezomib, lenalidomide, dexamethasone) induction/consolidation and lenalidomide maintenance in patients with newly diagnosed multiple myeloma (GMMG-HD6 trial, NCT02495922). The study compares four cycles induction therapy with VRD vs. VRD + elotuzumab, followed by standard intensification (i.e. mobilization and stem cell transplantation), two cycles consolidation with VRD/VRD + elotuzumab and lenalidomide maintenance +/- elotuzumab. The primary endpoint is determination of the best of four treatment strategies regarding progression-free survival. Here we present a first analysis of stem cell mobilization within this study. Patients and Methods: We performed a retrospective analysis of collection data on all patients who underwent peripheral blood stem cell (PBSC) collection between trial initiation in June 2015 and June 2016. Only patients with completely available datasets in respect of mobilization were considered (n=111). The vast majority of 99 patients (89%) received chemomobilization with CAD (cyclophosphamide, adriamycin, dexamethasone) followed by 5-10 µg G-CSF /kg body weight (bw) /d (starting day +9 until completion of PBSC collection), while in one case (1%) dexamethasone was omitted and in 10 cases (9%) cyclophosphamide mono was administered. One patient underwent steady-state mobilization with G-CSF only (10µg /kg bw /d). 55/111 patients received VRD (50%), whereas the remaining patients received VRD + elotuzumab. According to the recommendations of the study group, PBSCs for three stem cell transplants were to be collected. One transplant ideally consisted of ≥2.5 x10^6 CD34+ cells /kg bw, but in the event of poor mobilization as low as ≥2.0 x10^6 CD34+ cells /kg bw would be considered acceptable. Results: The median number of collected CD34+ cells was 10.4 x10^6 /kg bw (range 2.88 to 23.01 x10^6 /kg bw). Overall, 92 patients (83%) collected ≥7.5 x10^6 CD34+ cells /kg bw and another 12 patients (11%) collected between 6.0 and 7.5 x10^6 CD34+ cells /kg bw, resulting in three transplants, respectively. Only 7 patients (6%) collected below 6.0 x10^6 CD34+ cells /kg bw; 5 of them had been treated in the VRD-arm without elotuzumab. Due to insufficient PBSC mobilization after conventional treatment, 14 patients (13%) received a rescue mobilization with plerixafor, from which 12 patients collected ≥6.0 x10^6 CD34+ cells /kg bw. Overall, 7 serious adverse events (SAEs) occurred during mobilization phase, 4 of them in the study arm with elotuzumab. Conclusions: Cyclophosphamide-based chemomobilization after induction therapy with VRD is feasible. Efficient PBSC collection of ≥6.0 x10^6 CD34+ cells /kg bw could be performed in 104 of 111 patients (94%), with a low incidence of SAEs. The need for rescue mobilization was not higher than that of comparable previous GMMG treatment protocols. The addition of elotuzumab during induction phase did not impede PBSC collection. Disclosures Wuchter: Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hexal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Bertsch:Janssen: Research Funding; Celgene: Research Funding; Chugai: Research Funding. Munder:Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Fenk:Jansen: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding. Hillengass:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Celgene: Honoraria; BMS: Honoraria; Novartis: Research Funding; Sanofi: Research Funding. Raab:Novartis: Consultancy, Research Funding; BMS: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ho:Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Scheid:Medac: Other: Travel, accomodations or expenses; Baxalta: Honoraria; Amgen: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel, accomodations or expenses; Janssen: Consultancy, Honoraria; Celgene: Other: Travel, accomodations or expenses; BMS: Consultancy, Honoraria. Weisel:Onyx: Consultancy; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Novartis: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria. Goldschmidt:Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees.

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.

Phase I Study of Bortezomib(Bz), Pegylated Doxorubicin(DOX) and Dexamethasone(dex); ( VDD) with Escalating Doses of Cyclophosphamide(Cy) in Patients with Newly Diagnosed Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 617-617
Author(s):  
Melissa Alsina ◽  
Rachid Baz ◽  
Jose L Ochoa ◽  
Jyotishankar Raychaudhuri ◽  
Kara Kosakowski ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Phase I ◽  
Research Funding ◽  
Stem Cell Mobilization ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Long Term Outcome ◽  
Cell Mobilization ◽  
Grade 3

Abstract Abstract 617 Background: The VDD treatment regimen has been shown to be highly effective as initial therapy for multiple myeloma. Given the established synergy between bortezomib and alkylating agents, incorporating an alkylator to VDD may increase the depth of response and may improve long term outcome. We report the results from a Phase I trial combining VDD with escalating doses of cyclophosphamide ( CVDD) in patients (Pts) with newly diagnosed myeloma. Methods: Pts received Bz 1.0–1.3 mg/m2 on days 1, 4, 8, 11, DOX 30mg/m2 on day 4, Dex 20 mg on days 1, 2, 4, 5, 8, 9, 11, 12 and Cy 250-750 mg/m2 on day 1, for up to eight 21-day cycles, at four planned dose levels (Cy/Bz: 250/1.0, 500/1.0, 750/1.0, 750/1.3). Dose-escalation proceeded (three-pt cohorts) depending on dose-limiting toxicities (DLTs) grade 3 non-hematologic toxicity; thrombocytopenia with platelets <10,000/mm3 on >1 occasion despite transfusion support; Grade 4 neutropenia for >5 days and/or resulting in neutropenic fever; inability to receive cycle 2/day 1 dose due to drug-related toxicity). Pts with Grade 2 peripheral neuropathy (PNY) were excluded. Responses were assessed by International Working Group criteria. Pts with at least partial response ( PR) and standard risk cytogenetics could proceed to autologous stem cell transplant (ASCT) after 6 cycles. Responsive pts with high risk cytogenetics defined as the presence of one of the following at diagnosis; deletion of chromosome 13 by cytogenetics, hypodiploidy, or t (4;14), t(14;16) or deletion of 17 p by FISH, completed 8 cycles of therapy. Results: 26 pts have been enrolled to date: 12 in phase l, and 14 additional pts at the maximum planned dose (MPD). Median age 60 yrs, 62% men, 50% IgG MM, 81% with ISS stage II/III. Pts have received a median of 6 cycles; 17 have completed all 6-8 cycles, 1 has discontinued therapy. No DLTs were observed in the phase I portion of study. Dose reductions in cycle 2 and beyond have occurred in 31% of patients. Toxicities to date have been manageable, including all Grade 3/4 hematological toxicities (4-35%), Grade 3 hand foot syndrome( 15%), Grade 3 pneumonia (8%), Grade 3 UTI (8%), and Grade 3/4 metabolic (19%). There were no grade 3/4 PNY. There was 1 treatment-related mortality secondary to infection. The overall response rate in patients that have completed at least 4 cycles of therapy (ORR; ≥PR) is 90%, including 57% ≥VGPR, and 24% CR. ORR and VGPR rates were similar in patients with standard or high risk cytogenetics. Nine patients have proceeded to transplant and all have had successful stem cell mobilization with G-CSF alone. Conclusions: CVDD produces high quality responses and is well tolerated in newly diagnosed MM pts, regardless of their cytogenetic status or ISS stage. MPD has been reached at CY 750 mg/m2, Bz 1.3 mg/m2, DOX 30 mg/m2, and Dex 20 mg, with phase II enrollment ongoing. Stem cell mobilization has been successful in all pts, with transplant course in pts otherwise unremarkable. Updated efficacy will be presented at the meeting. Disclosures: Alsina: Millenium: Research Funding, Speakers Bureau; Ortho Biotech: Research Funding, Speakers Bureau.

A Phase III Study Of ASCT Vs Cyclophosphamide-Lenalidomide-Dexamethasone and Lenalidomide-Prednisone Maintenance Vs Lenalidomide Alone In Newly Diagnosed Myeloma Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 763-763 ◽  
Author(s):  
Antonio Palumbo ◽  
Francesca Gay ◽  
Andrew Spencer ◽  
Francesco Di Raimondo ◽  
Adam Zdenek ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Phase Iii ◽  
Study Endpoint ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Grade 3 ◽  
To Receive

Abstract Background High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). The introduction of novel agents challenged the role of ASCT at diagnosis. We conducted a multicenter 2X2 randomized trial comparing conventional chemotherapy plus lenalidomide with ASCT followed by maintenance with lenalidomide-prednisone (RP) or lenalidomide (R) alone in newly diagnosed young MM (NDMM) patients. Methods Eligible patients with NDMM ≤ 65 years were enrolled. All patients received Rd induction (four 28-day cycles of lenalidomide 25 mg day 1–21 and low-dose dexamethasone 40 mg day 1,8,15,22) followed by stem cell mobilization. Patients were randomized to receive consolidation with CRD [six 28-day cycles of cyclophosphamide (300 mg/m2 day 1,8,15), dexamethasone (40 mg days 1,8,15,22) and lenalidomide (25 mg days 1–21)] or MEL200-ASCT (melphalan 200 mg/m2 with stem-cell support). Patients were randomly assigned to receive subsequent maintenance with RP (28-day cycles of lenalidomide 25 mg days 1–21 plus prednisone 50 mg every other day) or R alone (28-day cycles of lenalidomide 25 mg days 1–21). Primary study endpoint was progression-free survival (PFS); secondary endpoints included safety, responses and overall survival (OS). Data cut off was May 30th, 2013. Results Three-hundred and eighty-nine patients were enrolled in the trial. Patient characteristics were well balanced between CRD (n=194) and MEL200-ASCT (n=195), and between R (n=195) and RP (n=194) arms. Median follow-up was 31 months. In the intent to treat (ITT) analysis, the median PFS was not reached with MEL200-ASCT and 28 months with CRD (the respective 3-year PFS was 60% vs. 38%, HR=0.62, 95%CI: 0.49-0.85, P=0.003). Median time from enrolment to maintenance was 14 months. In the population of patients eligible for maintenance, 2-year PFS from the start of maintenance was 73% for RP and 56% for R patients (HR= 0.57, 95%CI: 0.34-0.93; P=0.03). In the subgroup of patients who received MEL200-ASCT, 2-year PFS from the start of maintenance was 83% for patients who received RP and 64% for those who received R alone (HR=0.36 95%CI: 0.15-0.87, P=0.02). In the subgroup of patients who received CRD, 2-year PFS from the start of maintenance was 64% for patients who received RP and 47% for those who received R alone (HR=0.75, 95%CI: 0.40-1.39, P=0.36). At present, no differences in OS were noticed between patients randomised to received CRD or MEL200-ASCT, and between patients who received RP or R maintenance. As expected, the rates of grade 3-4 hematologic (85% vs. 26%, P<0.001) and non-hematologic (35% vs. 19%, P=0.003) adverse events (AEs) were higher in the MEL200-ASCT arm compared with the CRD arm. The main non-hematologic AEs were infections (18% vs. 5%, P=0.001) and gastrointestinal AEs (18% vs. 3%, P<0.001). Rates of grade 3-4 hematologic (8% vs. 7%, P=0.85) and non-hematologic (12% vs. 13%, P=0.88). AEs were similar in the RP and R arms. The main non-hematologic AEs in both RP and R groups were infections (3% vs. 3%). At present, 6 second primary malignancies and 3 cases of cutaneous basalioma have been reported. Conclusions MEL200-ASCT significantly prolonged PFS in comparison with CRD. At present no difference in OS was reported, this may be due to the low number of events and to the length of follow-up. The increase in toxicity with MEL200-ASCT did not adversely impact on efficacy. The addition of prednisone to lenalidomide maintenance significantly reduced the risk of progression in comparison with lenalidomide alone, without increasing the toxicity. Updated data with longer follow-up will be presented at the meeting. Disclosures: Palumbo: Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria. Gay:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Spencer:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Larocca:Celgene: Honoraria. Caravita:Celgene: Honoraria, Research Funding. Petrucci:Celgene: Honoraria. Hajek:Celgene: Honoraria; Celgene: Consultancy. Boccadoro:Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

scholarly journals Factors Influencing Long-Term Hematopoietic Function Following Autologous Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2186-2186
Author(s):  
Alissa Visram ◽  
Natasha Kekre ◽  
Christopher N. Bredeson ◽  
Jason Tay ◽  
Lothar B. Huebsch ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Research Funding ◽  
Infection Rates ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Significant Difference

Abstract Background/Objective: Mobilized peripheral blood hematopoietic progenitor cells are the most common stem cell source for autologous hematopoietic stem cell transplantation (auto-HSCT). Successful short-term stem cell engraftment requires collection of at least 2x106 CD34+ cells/kg. The American Society of Bone Marrow Transplantation (ASBMT) recommends a stem cell infusion target of 3-5 x106 cells/kg (Giralt et al. 2014). However, the number of CD34+ cells to reinfuse to ensure long-term engraftment has not been established. Plerixafor, a reversible CXCR4 antagonist, increases CD34+ cell yield at collection even in patients who are predicted poor mobilizers (PPM). Although plerixafor could be used universally for all collections, this may not be the most cost-effective strategy (Veltri et al. 2012). This study sought to determine the minimum number of CD34+ cells/kg required for adequate long-term hematopoiesis, identify factors associated with poor long-term hematopoiesis, and determine if plerixafor mobilization improved long-term peripheral blood counts. Methods: A retrospective chart review was conducted on patients who underwent auto-HSCT between January 2004 and September 2013 at The Ottawa Hospital, for management of hematological malignancies. Peripheral blood cell counts were collected from 1 to 5 years after auto-HSCT, or until disease relapse. Poor long-term hematopoiesis was defined as an ANC <1 x109/L, hemoglobin <100 g/L, or platelets <100 x109/L. Patients were stratified into groups based on the infused CD34+ concentration (in cells/kg), and the proportion of patients with poor long-term hematopoiesis at 1, 2, 3, 4, and 5 years post auto-HSCT was compared with chi square tests. Long-term clinical outcomes (platelet and packed red blood cell transfusions, and post auto-HSCT infection rates) were compared between plerixafor-mobilized patients and PPM (defined as patients with pre-collection CD34+ <2 x 106 cells/kg) with standard mobilization regimens. Results: This study included 560 patients who underwent auto-HSCT, 210 with multiple myeloma and 350 with lymphoma. At 1 and 5 years post auto-HSCT 377 and 104 patients were included, respectively. A dose dependent improvement 1 year after auto-HSCT was seen in patients who received 0-2.99 x 106 CD34+ cells/kg (24.4%, n= 41) compared to patients who received 5-9.99 x 106 CD34+ cells/kg (11%, n=154, p=0.051) and ³10 x 106 CD34+ cells/kg (4.5%, n=66, p=0.006). Though there was a trend towards lower CD34+ infusions and poorer hematopoietic function (see table 1), there was no statistically significant difference in hematopoietic function based on CD34+ infusion concentrations after 1 year post auto-HSCT. 10 patients received <2 x106 CD34+ cells/kg, of whom the rate of inadequate hematopoiesis was 33% at 1 year (n=6) and 0% (n=1) at 5 years post auto-HSCT. Factors that increased the risk of poor hematopoiesis over the course of study follow up, based on a univariate analysis, included advanced age (OR 1.189, p=0.05), multiple prior collections (OR 2.978, p=0.035), and prior treatment with more than two chemotherapy lines (OR 2.571, p=0.02). Plerixafor-mobilized patients (n=25), compared to PPM (n=197), had a significantly higher median CD34+ cell collection (4.048 x109/L and 2.996 x109/L cells/kg, respectively, p=0.005). There was no significant difference in overall cytopenias, transfusion requirements, or infection rates between plerixafor-mobilized and PPM patients over the course of the study follow up. Conclusion: Low pre-collection CD34+ counts, advanced age, multiple prior collections, and more than two prior chemotherapy treatments adversely affected long-term hematopoiesis post auto-HSCT. We support the transfusion target of 3-5 x 106 cells/kg, as proposed by the ASBMT, given that at 5 years post auto-HSCT there was no statistical or clinically significant difference in hematopoietic function with higher CD34+ infusion targets. While mobilization with plerixafor significantly increased overall CD34+ cell collection when compared with PPM, long-term hematopoietic function and clinical outcomes were not different. This finding supports the practise of limiting plerixafor use only to patients who are PPM, thereby facilitating adequate stem cell collection and early engraftment, as opposed to universal plerixafor mobilization. Disclosures Sabloff: Lundbeck: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Canada: Membership on an entity's Board of Directors or advisory committees; Gilead: Research Funding; Alexion: Honoraria.

scholarly journals Clonal Hematopoiesis Prevalence Increases throughout Treatment of Newly Diagnosed Multiple Myeloma Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1091-1091
Author(s):  
Tarek H. Mouhieddine ◽  
Chidimma Nzerem ◽  
Robert A. Redd ◽  
Andrew Dunford ◽  
Matthew Joseph Leventhal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Research Funding ◽  
Hematologic Malignancy ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Clonal Hematopoiesis ◽  
First Time ◽  
Time Point

Abstract Background: Recent studies have identified clinical and genomic factors contributing to worse clinical outcomes in patients with multiple myeloma (MM). Clonal hematopoiesis (CH) reflects the presence of somatic driver mutations in the blood or marrow of otherwise asymptomatic individuals. Using a variant allele frequency (VAF) cutoff of 2%, we recently reported CH in 21.6% of MM patients at the time of autologous stem cell transplant (ASCT) and found it was associated with shorter overall survival (OS) and progression-free survival (PFS) in those who did not receive maintenance therapy with an immunomodulatory drug (IMiD). However, this finding was based on a single tertiary center and only included MM patients who received ASCT. Methods: We studied a larger cohort of 986 newly diagnosed MM cases. Whole-exome sequencing (WES) data of peripheral blood and bone marrow samples of 986 MM patients (523 transplanted and 463 non-transplanted) from the Multiple Myeloma Research Foundation (MMRF) Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass, NCT0145429) study were analyzed. Both peripheral blood and tumor samples were analyzed to filter out myeloma mutations that could be contaminating the peripheral blood. Given the lower depth of coverage compared to prior targeted sequencing studies, small clones with a VAF below 2% were not detected. Altogether, the WES samples had a total depth of coverage of 117.68X. All data were analyzed using R version 3.5.0 (R Core Team). Results: Among the total cohort, 113 CH mutations were detected in 101/986 (10.24%) patients. CH was detected in 42/523 (8.03%) transplanted patients, compared to 59/463 (12.74%) non-transplanted patients. The most commonly mutated genes were DNMT3A, TET2, ASXL1, PPM1D, and TP53. The median age of the cohort was 63 years (range: 27 - 93), 60% were male, and median follow-up was 3.9 years (95% CI: 3.7 - 4.0). The presence of CH was associated with age (69 vs. 62 years, P &lt; 0.001). As expected, the median age of transplanted patients was lower (60 vs. 67 years) than in the non-transplanted group, which likely explains the higher prevalence of CH detected in the non-transplanted group. CH was associated with recurrent bacterial infections (P = 0.01) and increased cardiovascular disease (P = 0.006), but not with cerebrovascular disease (P = 0.74) or coagulopathies (P = 0.65). There was a trend towards worse PFS in non-ASCT patients with CH who were not treated with IMiDs (1.8 years) compared to non-CH IMiD-treated patients (2.7 years) (P &lt; 0.001). A CH effect on PFS was not detected in ASCT patients. OS was not different in those with or without CH in both ASCT and non-ASCT groups. 8 (0.8%) patients developed a second hematologic malignancy. CH at the time of MM diagnosis was not associated with an increased risk of developing a second hematologic malignancy (P = 0.58). To determine whether CH clones emerged or evolved during treatment, we examined serial samples from 52 patients (36 ASCT patients and 16 non-transplanted patients) with sequential samples. The median time between the first and second time point was 3.1 years (range: 1.0 - 5.4 years). At the first time point, only 3/52 (5.8%) patients had CH, but that number increased to 13/52 (25.0%) at the second time point. Five out of the 13 (38%) were non-transplanted patients. All but 1 patient were exposed to IMiDs. The most common emerging mutated gene was DNMT3A, found in 7 patient samples at the second time point, compared to 2 patients at the first time point. Conclusion: Using WES in a large cohort of newly diagnosed MM patients, we detected CH in 10.2% (VAF ≥ 2%) of patients. CH and non-IMiD treatment confers a shorter PFS in non-transplanted MM patients. However, throughout IMiD-based treatment, MM patients tend to acquire and/or expand previously undetected CH clones, particularly DNMT3A. The clinical significance of this clonal expansion during therapy is yet to be elucidated, and for now, this observation does not yet change clinical management. Figure 1 Figure 1. Disclosures Steensma: Novartis: Current Employment. Ebert: Deerfield: Research Funding; GRAIL: Consultancy; Exo Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Skyhawk Therapeutics: Membership on an entity's Board of Directors or advisory committees. Soiffer: NMPD - Be the Match, USA: Membership on an entity's Board of Directors or advisory committees; Gilead, USA: Other: Career Development Award Committee; Rheos Therapeutics, USA: Consultancy; Kiadis, Netherlands: Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics, USA: Other: Data Safety Monitoring Board; Precision Biosciences, USA: Consultancy; Jazz Pharmaceuticals, USA: Consultancy; Jasper: Consultancy; Takeda: Consultancy. Sperling: Adaptive: Consultancy. Getz: Scorpion Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; IBM, Pharmacyclics: Research Funding. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy.

scholarly journals G-CSF Plus Preemptive Plerixafor Versus Cyclophosphamide Plus G-CSF for Autologous Stem Cell Mobilization in Multiple Myeloma: Effectiveness, Safety and Cost Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5823-5823
Author(s):  
Ahmad Antar ◽  
Zaher Otrock ◽  
Mohamed Kharfan-Dabaja ◽  
Hussein Abou Ghaddara ◽  
Nabila Kreidieh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
Cell Yield ◽  
Fixed Dose ◽  
High Dose ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Introduction: The optimal stem cell mobilization regimen for patients with multiple myeloma (MM) remains undefined. Most transplant centers use either a chemo-mobilization strategy using cyclophosphamide (CY) and granulocyte-colony stimulating factor (G-CSF) or a steady state strategy using G-CSF alone or with plerixafor in case of mobilization failure. However, very few studies compared efficacy, toxicity and cost-effectiveness of stem cell mobilization with cyclophosphamide (CY) and G-CSF versus G-CSF with preemptive plerixafor. In this study, we retrospectively compared our single center experience at the American University of Beirut in 89 MM patients using fractionated high-dose CY and G-CSF as our past preferred chemo-mobilization strategy in MM patients with our new mobilization strategy using G-CSF plus preemptive plerixafor. The change in practice was implemented when plerixafor became available, in order to avoid CY associated toxicity. Patients and methods: Patients in the CY group (n=62) (Table 1) received either fractionated high-dose CY (n=56) (5g/m2 divided in 5 doses of 1g/m2 every 3 hours) or CY at 50mg/kg/day for 2 doses (n=6). G-CSF was started on day +6 of chemotherapy at a fixed dose of 300 µg subcutaneously every 12 hours. All patients in the plerixafor group (n=27) (Table 1) received G-CSF at a fixed dose of 300 µg subcutaneously every 12 hours daily for 4 days. On day 5, if peripheral blood CD34+ was ≥ 20/µl, apheresis was started immediately. Plerixafor (240 µg/kg) was given 7-11 hours before the first apheresis if CD34+ cell count on peripheral blood on day 5 was <20/µl and before the second apheresis if CD34+ cells on the first collect were <3х106/kg. The median number of prior therapies was 1 (range: 1-3) in both groups. Results: Compared with plerixafor, CY use was associated with higher median peak peripheral blood CD34+ counts (35 vs 111 cells/µl, P= 0.000003), and total CD34+ cell yield (7.5 х 106 vs 15.9 х 106 cells/kg, P= 0.003). All patients in both groups collected ≥4x106 CD34+ cells/Kg. Moreover, 60 (96.7%) and 46 (74.2%) patients in the CY group vs 24 (88.8%) and 6 (22%) patients in the plerixafor group collected >6х106 and >10x106 CD34+ cells/kg, respectively (P=0.16; P<0.00001). Only 4 (6.4%) patients required two apheresis sessions in the CY group compared to 11 (40%) in the plerixafor group (P=0.0001). Conversely, CY use was associated with higher frequency of febrile neutropenia (60% vs 0%; P<0.00001), blood transfusions (27% vs 0%; P<0.00001), platelets transfusion (25% vs 0%; P<0.00001) and hospitalizations (64% vs 0%; P<0.00001). No one required intensive level of care and all recovered. Autografting was successfully performed in all patients using high-dose melphalan with a median time from mobilization to the first transplant of 31 days (range: 16-156) in the CY group compared to 13 days (range: 8-40) in the plerixafor group (P=0.027); and median infused CD34+ cells were 7х106/kg (range: 3.1-15.3) versus 5.27 (2.6-7.45), respectively (P=0.002). The average total cost of mobilization using the adjusted costs based on National Social Security Fund (NSSF) prices in Lebanon in the plerixafor group was slightly higher compared with the CY group ($7964 vs $7536; P=0.16). Conclusions: Our data indicate robust stem cell mobilization in MM patients with either fractionated high-dose CY and G-CSF or G-CSF alone with preemptive plerixafor. The chemo-mobilization approach was associated with two-fold stem cell yield, slightly lower cost (including cost of hospitalization) but significantly increased toxicity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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