Plerixafor and G-CSF Versus Cyclophosphamide and G-CSF for Stem Cell Mobilization in Patients with Multiple Myeloma.

Abstract Abstract 2146 Poster Board II-123 Introduction: High dose melphalan and autologus stem cell transplant remains an effective treatment for patients with either early or refractory multiple myeloma (MM). Collection of sufficient numbers of stem cells for more than one transplant is optimal. G-CSF with chemotherapy, particularly cyclophosphamide (CY/G-CSF), has been a widely used and effective regimen for stem cell collection in MM. Plerixafor, a CXCR4 antagonist, when combined with G-CSF has been shown in a large randomized clinical trial to be superior to G-CSF alone. A comparison of plerixifor/G-CSF to CY/G-CSF is presented here. Materials and Methods: We performed a single institution retrospective analysis of 365 patients with MM who underwent stem cell mobilization and harvest at the University of Pennsylvania Abramson Cancer Center from January 2002 to December 2007. All patients were harvested early in the course of their disease. 76 patients were excluded from this analysis (23 had incomplete data on induction regimen, 19 had incomplete data on stem cell collection, 16 had incomplete data on mobilization regimen, 10 underwent allogeneic transplants, 2 had bone marrow rather than peripheral blood harvests, 2 had stem cells collected at an outside institution, 2 had chemotherapy mobilization other than CY and 2 had medical complications prior to harvest and after mobilization). Therefore, 289 patients were included in the analysis; 16 received plerixafor/G-CSF, 198 received CY/G-CSF, and 75 received G-CSF alone. Results: The median number of collected stem cells was 7.95 × 106 CD34+/kg in plerixafor/G-CSF group, 7.7 × 106 CD34+/kg in Cy/G-CSF group and 4.5 × 106 CD34+/kg in G-CSF alone group. The median number of apheresis days was 2 days, 2 days and 4 days respectively. The percentage of the patients who collected ≥ 6 × 106 CD34+/kg in < 3 apheresis was 63% (10/16), 62% (123/198) and 19% (14/75) respectively. The percentage of the patients who collected ≥ 6 × 106CD34+/kg <5 apheresis was 81% (13/16), 69% (136/198) and 23% (17/75) respectively. The mean CD34+/kg collected erither after CY/G-CSF or plerixafor/G-CSF was higher than G-CSF alone (p<0.0001 for each analysis). Conclusion: This analysis suggests that plerixafor/G-CSF and CY/G-CSF mobilization result in similar and adequate stem cell harvest numbers for autologous stem cell transplantation for MM. Both approaches are superior to G-CSF alone. The choice of plerixafor/G-CSF vs CY/G-CSF for stem cell mobilization will therefore depend on further analysis of the relative costs, toxicities and long term outcome of these regimens. Disclosures: Stadtmauer: genzyme: Consultancy.

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Stem Cell Mobilization after Various Induction Regimens in Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.5433.5433 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5433-5433

Author(s):

Jakub Radocha ◽

Vladimir Maisnar ◽

Miriam Lanska ◽

Jiri Hanousek ◽

Katerina Machalkova ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Conflicts Of Interest ◽

Rapid Development ◽

Autologous Transplantation ◽

Stem Cell Mobilization ◽

High Dose ◽

Cell Transplant ◽

Cell Mobilization ◽

Stem Cell Collection

Abstract Stem cell mobilization after various induction regimens in patients with multiple myeloma Introduction: Rapid development of novel therapies for multiple myeloma has led to a significant improvement in response to the treatment. Stem cell mobilization before autologous stem cell transplantation is a source of considerable costs of transplant procedure. Whether modern induction regimens affect outcome of stem cell mobilization has not been extensively studied. Aim: The goal of this study was to compare efficacy of stem cell mobilization after different induction regimens in patients with multiple myeloma. The primary goal was to compare CTD (cyclophosphamide, thalidomide, dexamethasone), CVD (cyclophosphamide, bortezomib, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) and regimens in terms of succesful stem cell collection. Methods: All patients with multiple myeloma who have been planned for stem cell collection and were treated with one of the above mentioned regimens were included in this retrospective analysis. The demographic data, amount of stem cells collected, number of days needed to reach the target collection were recorded. All patients received high dose cyclophosphamide 2,5 g/m2 prior to stem cell collection and were primed with G-CSF twice daily from day 5. The collection was started at day 10. Collection goal was 8x106/kg CD34+ cells. Results: 15 patients received CTD, 25 patients CVD and 16 patients VTD regimen before stem cell collection. Groups were comparable according to age, gender and myeloma stages. Mean collected cells at the end of collection were 9.2 (SD 2.8) for CTD, 12.3 (SD 5.6) for CVD and 10.1 (SD 2.1) for VTD (p=0.066). Mean daily harvest was 3.4, 8.0 and 7.6 x106/kg respectively (p=0.01). Mean days needed to reach desired harvest were 3, 2.25 and 1.6 days (p=0.001). No collection failure was observed. Conclusion: The best collection results were seen in patients after induction with CVD or VTD regimen. VTD regimen also required the least days for collection and seems to be most beneficial for cost of collection. CTD regimen shows the least efficacy in stem cell collection before autologous transplantation. All patients managed to harvest for at least one stem cell transplant. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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A Pilot Study of Eltrombopag Plus G-CSF for Human CD34+ Cell Mobilization in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplant

Blood ◽

10.1182/blood.v128.22.5815.5815 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5815-5815

Author(s):

Jacob P. Laubach ◽

Revital Freedman ◽

Robert A Redd ◽

Mason Tippy ◽

Kristen Cummings ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Pilot Study ◽

Adverse Events ◽

Median Number ◽

Clinical Development ◽

Stem Cell Mobilization ◽

Cd34 Cells ◽

Cell Mobilization

Abstract Background: Administration of recombinant human thrombopoietin (rhTPO) with G-CSF for stem cell mobilization is associated with high CD34+ stem cell yield, rapid neutrophil recovery following autologus transplantation (ASCT), and decreased red blood cell (rbc) and platelet (plt) transfusions (Solomo, G. et al. Blood 1999). However, clinical development of rhTPO was complicated by the formation of neutralizing anti-TPO antibodies (Li, J. et al. Blood 2001), prompting discontinuation of further clinical development of recombinant TPO. Eltrombopag (Elt) is an orally bioavailable small molecule thrombopoietin receptor (TPO-R) agonist approved by the FDA for treatment of chronic immune thrombocytopenic purpura (ITP). In vitro studies have demonstrated that Elt promotes megakaryocyte proliferation and differentiation of CD34+ bone marrow progenitor cells (Erickson-Miller CL Stem Cells 2009), suggesting that Elt might be a surrogate for rhTPO for stem cell mobilization. In this pilot trial, we evaluated the combination of Elt plus standard G-CSF and cyclophosphamide (C) for stem cell mobilization in patients (pts) with multiple myeloma (MM), a disease for which ASCT remains a standard of care (Blade et al. Blood 2010). Methods: Primary objectives included determination of the median number of CD34+ cells/kg mobilized and the maximum tolerated dose (MTD) of Elt. Pts had MM that was stable or responsive to at least two cycles of chemotherapy with plans for stem cell mobilization and ASCT. Four pts were to be enrolled in each of four dose escalation arms in which they received 0 (Arm D), 50 (Arm A), 100 (Arm B), or 150 mg (Arm C) of eltrombopag in combination with standard C + G-CSF. Adverse events (AEs) were graded by NCI-CTCAE v4. Results: 17 pts have been screened and enrolled to date. Two patients withdrew consent prior to receiving Elt and were excluded from statistical analysis. 15 patients have completed participation in the study to date and two patients remain to be enrolled in Arm C. The first subject in Arm A experienced delayed engraftment that was determined to be unrelated to ELT; rather, the event was attributed to administration of a one-time high dose of corticosteroid for management of a severe hypersensitivity reaction to DMSO that occurred during stem cell infusion. A second subject in Arm A had undergone mobilization with Elt prior to the previously described delayed engraftment event, and to ensure safety underwent a second mobilization with G-CSF and plerixafor. During ASCT, this patient received cells from the second mobilization procedure. While neither event met criteria for a dose-limiting toxicity, the protocol was amended such that three additional patients enrolled in Arm A underwent two rounds of mobilization - the first with Elt plus C and G-CSF and a second with G-CSF plus plerixafor - and received as part of ASCT cells mobilized with Elt. Each of these patients engrafted successfully. The median number of CD34+ cells/kg collected during the first collection day of apheresis in Arms D, A, B, and C was 8.0, 11.0, 15.3, and 26.4. The median total number of CD34+ stem cells collected following mobilization with Elt plus C and G-CSF in Arms D, A, B, and C was 13.2, 12.7, 15.4, and 26.4. The percentage of patients in Arms D, A, B, and C who achieved a target collection of 8 x 10^6 CD34+ stem cells in one collection day was 50, 60, 75, and 100%. There have been no severe adverse events related to Elt . Conclusions: Administration of Elt in combination with C plus G-CSF for stem cell mobilization in pts with MM undergoing ASCT was safe and well tolerated, with no DLTs or severe AEs attributable to Elt. The small size of this pilot study precludes formal statistical comparison of outcomes across treatment Arms, but there appears to be a trend toward increase in yield of CD34+ cells and decrease in apheresis procedures required with increasing doses of Elt. Disclosures Richardson: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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Effect of lenalidomide induction therapy on peripheral blood stem cell collection in patients undergoing autologous stem cell transplant for multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.6549 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 6549-6549

Author(s):

Divaya Bhutani ◽

Jeffrey A. Zonder ◽

Judith Abrams ◽

Voravit Ratanatharathorn ◽

Joseph P. Uberti ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplant ◽

Median Number ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Cd34 Cells ◽

Number Of Cycles ◽

Stem Cell Collection

6549 Background: Autologous stem cell transplant (ASCT) remains part of standard therapy for Multiple Myeloma (MM). Lenalidomide (LEN) is a newer, effective therapy for MM. It has been suggested that prior LEN therapy is associated with an increased risk of stem cell collection failure, particularly when only G-CSF is used for mobilization. Methods: We conducted a retrospective chart review of 310 consecutive MM pts who underwent pheresis to collect stem cells for first ASCT between July 1, 2007 and June 30, 2011 at the Karmanos Cancer Institute. We compared differences in quantity of CD34 cells collected, days needed to collect the target number of cells (> 2.5 x 10*6 CD34+ cells/kg), days to platelet and neutrophil engraftment. We also evaluated the association between CD34+ cells collected and the number of cycles of LEN therapy. Results: Of 310 patients, 90% were mobilized with only G-CSF initially. Patients were analyzed as two groups: LEN exposed (LEN(+); n = 128) and LEN naive(LEN(-); n = 182). Median age in both groups was 58 years. No differences in race, sex and MM stage distribution were observed between the two groups. The median number of stem cells collected in the LEN(+) group was significantly less than the LEN(-) group (6.46 vs. 7.56 x 10*6 CD34 cells/kg; p= 0.0004). In addition, the median number of pheresis sessions required for adequate stem cell collection were significantly more in the LEN(+)group as compared to LEN(-) group (2 vs.1 sessions; p=0.002). In the LEN(+) group, there was a negative correlation between CD34+ cells collected and the prior number of cycles of LEN (p=0.0001). There was no statistically significant excess in the number of stem cell collection failures with G-CSF in the LEN(+) group (7% vs. 4% p=0.31). All pts who failed collection after G-CSF were successfully collected with Cytoxan or Plerixafor priming. LEN exposure had no effect on post-ASCT neutrophil or platelet recovery. Conclusions: Although Lenalidomide exposure is associated with a slightly lower CD34+ stem cell yield and on average an extra session of pheresis when G-CSF is used for mobilization, collection failure is uncommon and post-ASCT engraftment is normal.

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Cyclophosphamide Overcomes the Suppressive Effect of LenalidomideTherapy on Stem Cell Collection in Preparation for Autologous Stem Cell Transplantation for Multiple Myeloma.

Blood ◽

10.1182/blood.v110.11.3024.3024 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3024-3024

Author(s):

Tomer Mark ◽

David Jayabalan ◽

Roger N. Pearse ◽

Jessica Stern ◽

Jessica Furst ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Induction Therapy ◽

Stem Cell Mobilization ◽

Cd34 Cells ◽

Cell Mobilization ◽

Stem Cell Collection

Abstract Multiple Myeloma (MM) therapy has evolved over recent years to include powerful new therapeutic agents. The goal for most patients with MM, however, still remains high-dose chemotherapy followed by autologous stem cell transplantations as this procedure has been proven to have a therapeutic benefit. Therefore, the selection of an induction therapy must take into consideration the potential impact on the ability to collect enough stem cells for future transplantation. Recent studies have discussed difficulty in collecting stem cells in patients receiving lenalidomide-based induction therapy using filgastrim (G-CSF) in preparation for autologous stem cell transplantation in MM. It also has been recommended that the duration of lenalidomide induction therapy be limited to 4–6 cycles, since longer treatment time can hinder collection yields. We sought to determine if the addition of cyclophosphamide (CTX) to G-CSF as a mobilization regimen could rescue the ability to collect adequate stem cells for at least two autologous stem cell transplants for patients who had induction therapy with the BiRD (Biaxin® [clarithromycin]/Revlimid® [lenalidomide]/dexamethasone) regimen. BiRD therapy is as follows for each 28-day cycle: Clarithromycin 500mg po BID for days 1–28, Lenalidomide 25mg po daily for days 1–21, and Dexamethasone 40mg po weekly on days 1, 8, 15, and 21. All patients had either Stage II or III MM by Salmon-Durie criteria and were treatment naïve. Patients were advised to undergo stem cell collection after either maximum disease response or disease plateau had been achieved. Prior to stem cell mobilization, BiRD therapy was held for a minimum of 14 days. Stem cell collection was performed after either G-CSF alone at a dose 10 mcg/kg/day for 5–10 consecutive days until a total of 10 × 106/kg CD34+ stem cells had been collected or with the addition of cyclophosphamide (CTX) at a dose of 3g/m2 once prior to the initiation of G-CSF therapy. A total of 28 patients underwent stem cell collection. Stem cell mobilization was attempted with G-CSF alone in 9 instances and with CTX+G-CSF in 20 instances (1 patient underwent mobilization with both G-CSF alone and CTX+G-CSF). In comparison to the G-CSF monotherapy, CTX+G-CSF yielded a significantly greater stem cell collection (mean CD34+ cells collected: 3.78 × 106/kg vs. 32.33 × 106/kg, P < 0.0001). Only 33% of patients who attempted stem cell mobilization with G-CSF alone obtained sufficient CD34+ cell yield vs. 100% of the patients mobilized with CTX+G-CSF (P < 0.0001). The extent of BiRD therapy prior to stem cell mobilization ranged from 2–27 cycles. The number of cycles of BiRD did not significantly impact the success rate of stem cell collection (P = 0.14). In conclusion, the patients mobilized with CTX+G-CSF had a higher number of CD34+ cells collected and were all able collect enough stem cells for two autologous transplants. There was no association with the duration of BiRD therapy and successful CD34+ cell collection. We therefore recommend continuing lenalidomide-based induction therapy until desired tumor reduction goal is achieved and using the CTX in addition to G-CSF to ensure successful stem cell harvest prior to autologous transplantation.

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Utility of Stem Cell Collection in Anticipation of Future Need for Autologous Stem Cell Transplant in Follicular Lymphoma Patients

Blood ◽

10.1182/blood.v118.21.1926.1926 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1926-1926

Author(s):

Robin R. Klebig ◽

Stephen M. Ansell ◽

Joseph P. Colgan ◽

Dennis A. Gastineau ◽

Thomas M. Habermann ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Autologous Stem Cell Transplant ◽

Stem Cell Mobilization ◽

Cell Transplant ◽

Collection Cost ◽

Cell Mobilization ◽

The Cost ◽

And Storage ◽

Stem Cell Collection

Abstract Abstract 1926 Background: Follicular lymphoma (FL) is the second most common non Hodgkin lymphoma in the United States, comprising up to 30% of all non Hodgkin lymphomas. Typically an indolent disease, relapses are common. High dose therapy followed by autologous stem cell transplant is an option that has shown to produce prolonged progression-free and relapse-free survival in patients who relapse. Adequate bone marrow reserve for peripheral stem cell mobilization has been shown to be adversely effected by prior regimens such as fludarabine and radioimmunotherapy. Concerns regarding stem cell mobilization at the point of relapse have led some to collect stem cells early in the course of disease to allow for potential subsequent transplant after relapse. Recent advances in stem cell mobilization have resulted in a 3% collection failure rate for lymphoma patients at the point of planned transplant at our institution versus a historical rate of up to 30%. We studied the utilization of stem cells collected for potential future use in FL patients in remission or prior to therapy at the point of relapse or progression in order to determine the utility of this approach. Methods: Record review of patients diagnosed with FL through the Mayo Clinic Tumor Registry and the Mayo Clinic Lymphoma Data Base who had cryopreserved stem cells for potential future transplant at relapse. Cost of stem cell storage at our institution was reviewed as was the subsequent use of the collected cells. Results: 73 patients with FL had stem cells collected and stored. 37 (51%) were collected prior to a double dose yttrium-90 (90Y) ibritumomab tiuxetan trial for relapsed lymphoma as required by the study. The median age at collection of this group was 56 years (range 28–70). Stem cells remain in storage for a median of 44 months (range 8–119). The median cost of cryopreservation and storage is $4,094 based on the median storage time of 44 months (range $3,628 to 5,065) with a collection cost of $3,524.20 and an annual storage fee of $155.39. This does not include the cost of filgrastim for mobilization, nor line placement. At 5 years, 60% of the cells were not utilized, and at 10 years, 56% of the cells were not utilized. 36 (49%) of the total number of patients were not part of the double dose 90Y ibritumomab tiuxetan trial, but were collected in remission for possible future use or in the setting of relapsed, progressed or transformed disease for potential future transplant. Five of these patients required the use of plerixafor for adequate mobilization. The median age at collection of this group was 47 years (range 24–76). Stem cells remain in storage for a median of 39 months (range 2–128). The median cost of cryopreservation and storage is $4,029 based on the median storage time of 39 months (range $3,550 to 5,182) with a collection cost of $3,524.20 and an annual storage fee of $155.39. This does not include the cost of filgrastim or plerixafor for mobilization, nor line placement. At 5 years, 89% of these cells were not used, and at 10 years, 71% of cells were not used. Conclusion: The utilization of stem cells collected early in the course of FL patients is low, with the majority of cells not being utilized at 10 years. Given improved mobilization techniques resulting in 97% efficacy of stem cell collection at relapse, routine collection and storage of stem cells early in the course FL is not recommended. Disclosures: Micallef: Genzyme: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Collection of Peripheral Blood Stem Cells in Patients with Multiple Myeloma after Stem Cell Transplant: A Single Institution Experience

Blood ◽

10.1182/blood.v126.23.5435.5435 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5435-5435

Author(s):

Umang Swami ◽

Lindsay Dozeman ◽

Annick Tricot ◽

Kamal Kant Singh Abbi ◽

Guido J Tricot

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Peripheral Blood ◽

Median Number ◽

Cell Transplant ◽

Peripheral Blood Stem Cells ◽

Blood Stem Cells ◽

History Of ◽

Stem Cell Collection

Abstract Background Autologous stem cell transplant is the standard of care for eligible multiple myeloma patients. However, many patients relapse with passage of time. These patients often do not have any or have inadequate numbers of previously harvested stem cells. The question still comes up frequently whether peripheral blood stem cells can be successfully collected from patients with history of prior transplant and what is the best approach. Herein, we report the results from our institution. Patients and Methods Records of patients with multiple myeloma who received transplant at our institute between 03/01/12 -07/09/15 dates were reviewed. Recorded data included disease stage, prior transplant and chemotherapies, stem cell mobilization strategies and time to engraftment. Student T-test was performed on reviewed data. Results A total number of 21 patients (7 male and 14 female) with multiple myeloma and prior transplant underwent peripheral blood stem cell collection. Median age at diagnosis was 52.1 years (range 36-71 years). Each patient had at least 2 prior rounds of chemotherapy with a median of 4 prior lines of chemotherapies (range 2-6). One patient had a prior history of allotransplant and remainder had at least one prior autotransplant. ISS staging at diagnosis included 5 patients with Stage 1, 2 patients with Stage 2, 5 patients with Stage 3 and stage was not available for 8 patients. One patient had plasma cell leukemia. Disease subtypes included two patients with IgA kappa, one with IgA lambda, nine with IgG kappa, two with IgG lambda, five with kappa light chain, one with lambda light chain and one with non-secretory disease. 33% of patients had high risk cytogenetics at time of stem cell collection. The total number of prior transplants before stem cell collection was 25 with a median of 1 transplant (range 1-2). Median age at the time of collection was 59.3 years (range 43-81). Disease status at time of salvage transplant included complete response in 5 patients, very good partial response in 2, partial response in 9 and stable disease in 5 patients. Filgrastim with plerixafor was used for mobilization in 15 patients, filgrastim, plerixafor and pegfilgrastim in 5 patients and filgrastim with pegfilgrastim in 1 patient. A median number of 3 doses of plerixafor (range 0-5) were used. Median stem cell collection dose was 9.75 X 106/kg CD34 cells (range 3.29-24.8 X 106/kg) and median number of collection days was 3 (range 1-5). All patients received salvage transplants. Engraftment occurred at a median of 12 days (range 10-27). The 21 patients received a total number of 30 transplants after collection with a median of 1 transplant (range 1-2). Prior to collection, D-PACE was administered to 10 patients, VDT-PACE to 2 patients, VCD to 1 patient and growth factors only to 8 patients. 5/8 patients who were mobilized with only growth factors had baseline platelet count of < 130,000. Patients receiving D-PACE had a median collection of 13.55 X 106 cells as compared to 5.70 X 106 cells without it (p<0.004). Conclusions Our experience shows that collecting peripheral blood stem cells after prior transplantation in patients with multiple myeloma is very feasible even in patients with multiple lines of chemotherapies. Addition of D-PACE as chemo-mobilization strategy has proved to be effective if platelet count is normal at baseline. Disclosures No relevant conflicts of interest to declare.

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Delayed Neutrophil Engraftment in Patients Receiving Daratumumab As Part of Their First Induction Regimen for Multiple Myeloma

Blood ◽

10.1182/blood-2019-131380 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4505-4505

Author(s):

Abdullah S. Al Saleh ◽

M Hasib Sidiqi ◽

Morie A. Gertz ◽

Eli Muchtar ◽

Martha Q. Lacy ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Median Time ◽

Research Funding ◽

Stem Cell Mobilization ◽

Induction Regimen ◽

Cell Mobilization ◽

Stem Cell Collection ◽

Neutrophil Engraftment

Introduction: Daratumumab is a human immunoglobulin (IgG-κ) that targets CD38 abundantly expressed on plasma cells. Data is emerging to show its efficacy as part of induction therapy for newly diagnosed multiple myeloma (MM) patients. Hematopoietic stem cells have been shown to express CD38 on the cell surface and therefore during mobilization, there is a theoretical risk of circulating daratumumab binding to and having downstream effects on these cells. Methods: We conducted a retrospective review of MM patients treated with daratumumab prior to stem cell collection and autologous stem cell transplant (ASCT) to identify any effects daratumumab therapy may have on the efficacy of the stem cells in bone marrow recovery. The study was conducted at Mayo Clinic Rochester from February 2018 to May 2019. Granulocyte colony-stimulating factor was the preferred agent used for stem cell mobilization and plerixafor was added in a demand-adapted fashion. All patients received melphalan infused at day -1 before their ASCT and the decision about dosing (200mg/m2 vs 140mg/m2) was at the physicians' discretion. Neutrophil engraftment was defined as the first date of three consecutive neutrophil counts >0.5 x 10^9/L and platelet engraftment was defined as the first date of three consecutive platelet counts >50 x 10^9/L in the absence of platelet transfusion in the preceding 7 days. Results: We identified 12 patients who received daratumumab as part of their first induction regimen (daratumumab cohort) and compared them to 129 patients who did not receive daratumumab prior to stem cell mobilization and transplant during the study period (no daratumumab cohort). Of the daratumumab cohort, 11 patients received daratumumab, ixazomib, lenalidomide, and dexamethasone and one received daratumumab, cyclophosphamide, bortezomib and dexamethasone. No differences were noted in terms of melphalan dose or the number of CD34+ stem cell infused. The median time from the last dose of daratumumab to stem cell collection was 3.9 weeks. In patients receiving daratumumab, the median time for neutrophil engraftment was three days longer compared with those who did not receive daratumumab (median of 19 days vs. 16 days, P=0.017) (Figure 1, A). Median platelet engraftment was delayed by one day, although this was not statistically significant (median of 18 days vs. 17 days, p=0.12) (Figure 1, B). A total of 6 patients (50%) from the daratumumab cohort and 52 (40%) from the no daratumumab cohort required hospital admission. Of these admissions, there was no difference between the two groups in rates of admission for fever (50% in the daratumumab group vs. 42% in the no daratumumab group, P=0.7). Conclusion: Our case series provides the first report of daratumumab delaying engraftment post transplant in myeloma patients receiving it prior to stem cell collection. A better characterization of this phenomenon is important given the increasing use of daratumumab as front line therapy prior to ASCT in patients with myeloma. Disclosures Gertz: Prothena: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Spectrum: Honoraria, Research Funding; Alnylam: Honoraria; Ionis: Honoraria. Lacy:Celgene: Research Funding. Kapoor:Sanofi: Consultancy, Research Funding; Glaxo Smith Kline: Research Funding; Cellectar: Consultancy; Janssen: Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Celgene: Honoraria. Dispenzieri:Alnylam: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.

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Bortezomib Added to the Standard Mobilization Regimen of G-CSF and High-Dose Cyclophosphamide Is a Safe and Effective Combination for a High Yield Stem Cell Collection While Promoting Further Tumor Mass Reduction in Myeloma.

Blood ◽

10.1182/blood.v108.11.2953.2953 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2953-2953 ◽

Cited By ~ 2

Author(s):

Jessica L. Stern ◽

Brian Di Carlo ◽

Michael W. Schuster ◽

Tsiporah B. Shore ◽

John G. Harpel ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Alkylating Agents ◽

Pegylated Liposomal Doxorubicin ◽

Stem Cell Mobilization ◽

High Dose ◽

Cell Mobilization ◽

Grade 3 ◽

Stem Cell Collection

Abstract Standard stem cell mobilization regimens for multiple myeloma patients include G-CSF alone or in combination with high dose cyclophosphamide. Given the known in vitro and in vivo synergy between alkylating agents and proteosome inhibitors, we sought to optimize the potential for concurrent cytoreduction by adding bortezomib to the mobilization regimen. Five evaluable patients, whose prior therapy consisted of six cycles of a 21-day treatment with bortezomib/dexamethasone +/− pegylated liposomal doxorubicin, were mobilized. They received IV push bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 in combination with high-dose cyclophosphamide at 3mg/m2 and MESNA on day 8. G-CSF was given for 10 consecutive days starting on day 9. One patient began this regimen in nCR, two were in PR, and two were in CR by urine and serum immunofixation and bone marrow evaluation. Stem cells were easily harvested from each of the five patients. The number of CD34+ cells collected far exceeded the amount normally mobilized with cyclophosphamide and/or G-CSF alone, with four out of 5 patients collected in a single day. The two patients who began the mobilization cycle in PR continued to respond positively. Their protein levels dropped an additional 8.9 and 14.6 percent respectively during the last cycle. The patient who began mobilization in nCR achieved a CR by the end of treatment. Some expected toxicities associated with high dose cyclophosphamide and G-CSF occurred. All patients experienced grade 3 and 4 cytopenias, however, they recovered and were able to continue on to transplant. Serious adverse events of grade 3 chest pain (non-cardiac), grade 4 pneumonia, and grade 4 febrile neutropenia also occurred. Bortezomib in addition to high dose cyclophosphamide followed by G-CSF is a novel, well-tolerated and efficacious combination for stem cell mobilization in patients with multiple myeloma. This regimen not only yields a high number of stem cells within a short collection time, but may further cytoreduce disease as well. Stem Cell Collection Patients Days Required for Collection CD34+ Stem Cells (million/kg) 1 1 21.2 2 1 47.4 3 1 22 4 1 17.9 5 4 40.6

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Neutropenic Fever During Stem Cell Mobilization Is Associated with Decreased CD34+ Cell Collection and Poor Survival Following Autologous Stem Cell Transplantation,

Blood ◽

10.1182/blood.v118.21.4053.4053 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4053-4053

Author(s):

Hien Duong ◽

Brian J. Bolwell ◽

Lisa Rybicki ◽

John William Sweetenham ◽

Brad Pohlman ◽

...

Keyword(s):

Stem Cell ◽

Hodgkin Lymphoma ◽

Neutropenic Fever ◽

Stem Cell Mobilization ◽

Cell Transplant ◽

Long Term Outcome ◽

Increased Risk ◽

Cd34 Cells ◽

Cell Mobilization ◽

Stem Cell Collection

Abstract Abstract 4053 High-dose chemotherapy followed by autologous stem cell transplant can improve long-term outcome of patients with relapsed non-Hodgkin and Hodgkin lymphoma. Stem cell mobilization with chemotherapy in addition to G-CSF improves stem cell collection, however it is also associated with increased risk of neutropenic fever. We analyze whether hospitalization for neutropenic fever (NF) affects outcomes after transplantation. From 1/1998 to 12/2008, 599 patients underwent chemotherapy priming with etoposide + G-CSF (27 patients also received rituximab). Forty five (8%) did not proceed to transplant. Of the 554 (92%) patients who were transplanted, the median age was 51 years, and 348 (63%) were male. The diagnoses were 422 non-Hodgkin lymphoma (63%) and 132 Hodgkin lymphoma (24%). A majority of these patients (92%) had received 3 or less prior chemotherapy regimens. Only 6% had been exposed to fludarabine therapy. Most patients had chemosensitive disease (88% were in CR or PR) at time of transplant. For preparative regimen: 517 (93%) received busulfan/etoposide/cyclophosphamide, 32 (5.8%) received melphalan, 5 (0.9%) received other chemotherapy. Of the transplanted patients, 121 (21.8%) were admitted for NF during stem cell mobilization. The median duration of admission for NF was 5 days (range 1–20). Six (5%) patients had bacteremia, 1 (<1%) had parainfluenza virus pneumonia, and the remainder 114 (94%) did not have any infection source or organism identified. The patients hospitalized for NF had significantly lower CD34+ cell collection (7.49 × 10^6 CD34 cells vs. 9.36 × 10^6, P=0.029) and lower CD34+ cell dose (7.34 × 10^6 CD34 cells/kg vs. 8.60 × 10^6 CD34+ cells/kg, P=0.047) despite more apheresis days required for collection (4 days vs. 3 days, P=0.01). Following transplant hospitalization, the 30-day readmission rate was higher in NF patients (16.8% compared to 8.8%, P=0.012). Hospitalization for NF was also associated with worse survival as shown below: In conclusion, admission for neutropenic fever during stem cell mobilization is associated with significantly increased number of apheresis days required for adequate stem cell collection, lower CD34+ cell collection, higher 30-day re-admission rates, and poorer survival. Disclosures: No relevant conflicts of interest to declare.

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Impact of Induction Treatment on Stem Cell Collection: A COVID Related Study

Blood ◽

10.1182/blood-2021-149812 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4848-4848

Author(s):

Brad Rybinski ◽

Ashraf Z. Badros ◽

Aaron P. Rapoport ◽

Mehmet Hakan Kocoglu

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Research Funding ◽

Median Number ◽

Cell Transplant ◽

Cd34 Cells ◽

Significant Difference ◽

Number Of Cycles ◽

Time Required ◽

Stem Cell Collection

Abstract Introduction: Standard induction therapy for multiple myeloma consists of 3-6 cycles of bortezomib, lenalidomide, and dexamethasone (VRd) or carfilzomib, lenalidomide and dexamethasone (KRd). Receiving greater than 6 cycles of a lenalidomide containing regimen is thought to negatively impact the ability to collect sufficient CD34+ stem cells for autologous stem cell transplant (Kumar, Dispenzieri et al. 2007, Bhutani, Zonder et al. 2013). Due to the COVID-19 pandemic, at least 20 patients at University of Maryland Greenebaum Comprehensive Cancer Center (UMGCC) had transplant postponed, potentially resulting in prolonged exposure to lenalidomide containing induction regimens. Here, in the context of modern stem cell mobilization methods, we describe a retrospective study that suggests prolonged induction does not inhibit adequate stem cell collection for transplant. Methods: By chart review, we identified 56 patients with multiple myeloma who received induction with VRd or KRd and underwent apheresis or stem cell transplant at UMGCC between 10/1/19 and 10/1/20. Patients were excluded if they received more than 2 cycles of a different induction regimen, had a past medical history of an inborn hematological disorder, or participated in a clinical trial of novel stem cell mobilization therapy. We defined 1 cycle of VRd or KRd as 1 cycle of "lenalidomide containing regimen". In accordance with routine clinical practice, we defined standard induction as having received 3-6 cycles of lenalidomide containing regimen and prolonged induction as having received 7 or more cycles. Results: 29 patients received standard induction (Standard induction cohort) and 27 received prolonged induction (Prolonged induction cohort) with lenalidomide containing regimens. The median number of cycles received by the Standard cohort was 6 (range 4-6), and the median number of cycles received by the Prolonged cohort was 8 (range 7-13). The frequency of KRd use was similar between patients who received standard induction and prolonged induction (27.58% vs. 25.93%, respectively). Standard induction and Prolonged induction cohorts were similar with respect to clinical characteristics (Fig 1), as well as the mobilization regimen used for stem cell collection (p = 0.6829). 55/56 patients collected sufficient stem cells for 1 transplant (≥ 4 x 10 6 CD34 cells/kg), and 40/56 patients collected sufficient cells for 2 transplants (≥ 8 x 10 6 CD34 cells/kg). There was no significant difference in the total CD34+ stem cells collected at completion of apheresis between standard and prolonged induction (10.41 and 10.45 x 10 6 CD34 cells/kg, respectively, p = 0.968, Fig 2). Furthermore, there was no significant correlation between the number of cycles of lenalidomide containing regimen a patient received and total CD34+ cells collected (R 2 = 0.0073, p = 0.5324). Although prolonged induction did not affect final stem yield, prolonged induction could increase the apheresis time required for adequate collection or result in more frequent need for plerixafor rescue. There was no significant difference in the total number of stem cells collected after day 1 of apheresis between patients who received standard or prolonged induction (8.72 vs. 7.96 x 10 6 cells/kg, respectively, p = 0.557). However, patients who received prolonged induction were more likely to require 2 days of apheresis (44% vs. 25%, p = 0.1625) and there was a trend toward significance in which patients who received prolonged induction underwent apheresis longer than patients who received standard induction (468 vs 382 minutes, respectively, p = 0.0928, Fig 3). In addition, longer apheresis time was associated with more cycles of lenalidomide containing regimen, which neared statistical significance (R 2 = 0.0624, p = 0.0658, Fig 4). There was no significant difference between standard and prolonged induction with respect to the frequency of plerixafor rescue. Conclusions: Prolonged induction with lenalidomide containing regimens does not impair adequate stem cell collection for autologous transplant. Prolonged induction may increase the apheresis time required to collect sufficient stem cells for transplant, but ultimately clinicians should be re-assured that extending induction when necessary is not likely to increase the risk of collection failure. Figure 1 Figure 1. Disclosures Badros: Janssen: Research Funding; J&J: Research Funding; BMS: Research Funding; GlaxoSmithKline: Research Funding.

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