Plerixafor For Stem Cell Mobilization Research Articles

Cost-Effectiveness Analysis of Motixafortide Versus Plerixafor in Stem Cell Mobilization for Autologous Transplantation in Patients with Multiple Myeloma

Introduction: The Phase 3 GENESIS trial (NCT03246529) compared the efficacy and safety of motixafortide and granulocyte-colony stimulating factor (M+G) to placebo + G (PBO+G) for the mobilization of hematopoietic stem cells (HSCs) prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Compared with PBO+G, M+G significantly increased the proportion of patients who were able to successfully mobilize ≥6x106 CD34+ cells/kg for ASCT within 2 apheresis days (92.5% vs. 26.2%; p<0.0001). In a cost-effectiveness model (CEM) based on the GENESIS trial, M+G yielded additional quality-adjusted life years (QALYs) and cost savings relative to G alone from a United States (US) healthcare payer perspective (Lamotte et al. (2022) Value Health 25(7): S346). Plerixafor + G (P+G) is also used for HSC mobilization prior to ASCT in patients with MM. To date, M+G and P+G have not been directly compared in head-to-head trials; therefore, the relative efficacy and cost effectiveness of these therapies is currently unknown. Methods: The Bucher method was used to assess the relative efficacy of M+G in the GENESIS trial and P+G in the Phase 3 AMD-3102 trial (NCT00103662), with the PBO+G arms of both trials used as a common comparator. Risk ratios (RRs) were derived for binary trial endpoints (i.e., proportion with mobilization of ≥6x106 CD34+ cells/kg within 1-4 apheresis days, successful engraftment, use of rescue therapy, proportion who underwent ASCT, incidence of serious adverse events [SAEs]) and mean differences were derived for continuous trial endpoints (i.e., number of study drug doses received, frequency and amount of G doses, and number of apheresis sessions). The RRs were then used to update the CEM to compare the cost effectiveness of M+G and P+G from a US healthcare payer perspective over a lifetime horizon; model assumptions and sources for unit costs and quality of life scores were unchanged from the previously published CEM. Results: The mean age at baseline was 59-60 years in GENESIS and 58 years in AMD-3102; heterogeneity was observed for the mean time since diagnosis (6-7 vs. 11-12 months), prior radiotherapy (10%-11% vs. 27%-31%), and the ethnic and sex distribution of the PBO+G arms (White: 95% vs. 83%; males: 57% vs. 70%). Notably, prior lenalidomide use was markedly lower in AMD-3102 (<10%) than in GENESIS (70%), which likely contributed to the higher mobilization rates in the AMD-3102 PBO+G arm than in the GENESIS PBO+G arm. In the Bucher analysis, healthcare resource utilization (HRU) outcomes significantly favored M+G during primary mobilization, including less frequent administration of G (mean difference [MD]: -0.97; 95% CI -1.43, -0.50; p=0.0001), lower G doses (MD: -920 mcg; 95% CI -1,368, -471; p=0.0001), and fewer apheresis sessions (MD: -0.98; 95% CI -1.34, -0.63; p<0.0001) (Table 1). The proportion of patients with successful mobilization of ≥6x106 CD34+ cells/kg within 1 apheresis day was significantly greater with M+G (88.8%) than with P+G (54.2%; RR 2.97; 95% CI 1.08, 8.17; p=0.0341). Similar results were observed between groups for other outcomes, including ASCT rates (RR 1.06; 95% CI 0.93, 1.21; p=0.4124), engraftment durability by 100 days (RR 0.98; 95% CI 0.87, 1.11; p=0.7894), and SAE rate (RR 2.36; 95% CI 0.26, 21.05; p=0.4521); analyses were limited to publicly available data for P+G, and were not feasible for the use of rescue therapy because of insufficient sample size. In the cost-effectiveness analysis, M+G was dominant to P+G over a lifetime horizon, resulting in additional QALYs (+0.0358) and lower total costs (-$17,378 USD; Table 2) as per base case deterministic results. The key cost drivers were the probability of successful transplantation, long-term maintenance costs, and the time to engraftment in poor mobilizers. In a probabilistic sensitivity analysis, M+G was dominant in 66% of simulations and 92% cost effective at a WTP threshold of $50,000 per QALY. Conclusions: The results of this analysis show that the use of M+G was associated with significantly lower HRU relative to P+G for the mobilization of HSCs prior to ASCT in patients with MM, as well as significantly greater successful mobilization of ≥6x106 CD34+ cells/kg within 1 apheresis day. Cost-effectiveness analysis results showed that M+G was dominant to P+G, yielding additional QALYs and net cost savings over a lifetime horizon from a US healthcare payer perspective. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Use of Plerixafor for Stem Cell Mobilization in the Setting of Autologous and Allogeneic Stem Cell Transplantations: An Update [Corrigendum

[This corrects the article DOI: 10.2147/JBM.S307520.].

Prophylactic Peripheral Blood Stem Cell Collection in Patients with Extensive Bone-Marrow Infiltration of Neuroendocrine Tumours Prior to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE.

Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity.

Use of Plerixafor for Stem Cell Mobilization in the Setting of Autologous and Allogeneic Stem Cell Transplantations: An Update.

Mobilization failure is an important issue in stem cell transplantations. Stem cells are yielded from the peripheral blood via apheresis. Granulocyte colony-stimulating factor (G-CSF) is the most commonly used mobilization agent among patients and donors. G-CSF is administered subcutaneously for multiple days. However, patients with mobilization failure cannot receive autologous stem cell transplantation and, therefore, cannot be treated adequately. The incidence rate of mobilization failure among patients is about 6–23%. Plerixafor is a molecule that inhibits the binding of chemokine receptor-4 with stromal-cell-derived factor-1, thereby resulting in the release of CD34+ cells in the peripheral blood. Currently, plerixafor is used in patients with mobilization failure with G-CSF and is administered subcutaneously. Several studies conducted on different clinical settings have shown that plerixafor is effective and well tolerated by patients. However, more studies should be conducted to explore the optimal approach for plerixafor in patients with mobilization failure. The incidence of mobilization failure among donors is lower. However, plerixafor is not approved among donors with mobilization failure. Moreover, several clinical studies in donors have shown a beneficial effect of plerixafor. In addition, the adverse events of plerixafor are mild and transient, which can overcome the adverse events due to G-CSF. This review assessed the current role and effects of plerixafor in stem cell mobilization for autologous and allogeneic stem cell transplantations.

Pharmacokinetic-Guided Therapeutic Dose Monitoring (TDM) of Busulfan Reduces Relapse of Non-Hodgkin Lymphoma (NHL) Patients Undergoing Autologous Stem Cell Transplantation (ASCT)

Introduction Busulfan (Bu) is integral to many preparative regimens for hematopoietic stem cell transplantation but its metabolism is variable and unpredictable. At our institution, Bu was administered with fixed weight-based dosing (WBD) for NHL patients (pts) undergoing ASCT until 2014 when we initiated a prospective clinical trial (NCT01959477) with pharmacokinetic (PK)-guided therapeutic dose monitoring (TDM) of Bu with cyclophosphamide (Cy) and etoposide (VP16). We subsequently adopted this practice as a standard for all NHL pts. Here, we compare outcomes of NHL pts who received ASCT with WBD vs. PK-directed TDM. Methods We collected clinical features and outcomes of 336 adult NHL pts who underwent ASCT with Bu/Cy/VP16 using WBD (n=258) from 1/2007-12/2013 or TDM from 5/2014-12/2017 (n=78) excluding mantle cell lymphoma. For WBD, Bu was given at 2.8 mg/kg q24 hours on day -9 to -6. For TDM, plasma Bu concentration was serially determined via an in-house liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay as previously described and externally validated. Bu area under the curve (AUC) after first dose was calculated for each pt and used to adjust subsequent doses to target a daily AUC of 4500 μM-minute. Results Baseline features of WBD and TDM pts were similar, although more TDM pts received plerixafor for stem cell mobilization and TDM pts were more often categorized as having a complete remission (CR) prior to ASCT (Table), likely due to more use of PET scan. To adjust for differences, propensity-matched cohorts of WBD and TDM pts were also studied (Table). 36% of TDM pts had increases and 41% had decreases in Bu dose. As shown in the Figure, 24 months after ASCT, relapse was significantly lower with TDM vs. WBD (19% vs. 38%, P = 0.004) and relapse-free survival (RFS) was also improved (69% vs. 55%, P = 0.038). Overall survival (OS) did not differ between WBD and TDM cohorts, likely due to subsequent therapy at the time of relapse. Propensity matched cohorts displayed similar patterns of outcomes. For pts in CR at time of ASCT, RFS did not differ between WBD and TDM (P = 0.79) whereas RFS was improved for pts in Conclusion Compared to WBD, PK-directed TDM of Bu safely reduces relapse when used in combination with Cy + VP16 for NHL pts undergoing ASCT, particularly for pts in

Results of a Prospective Randomized, Open-Label, Noninferiority Study of Tbo-Filgrastim (Granix) versus Filgrastim (Neupogen) in Combination with Plerixafor for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma and Non-Hodgkin Lymphoma

Autologous hematopoietic stem cell transplantation (auto-HSCT) improves survival in patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). Traditionally, filgrastim (Neupogen; recombinant G-CSF) has been used in as a single agent or in combination with plerixafor for stem cell mobilization for auto-HSCT. In Europe, a biosimilar recombinant G-CSF (Tevagrastim) has been approved for various indications similar to those of reference filgrastim, including stem cell mobilization for auto-HSCT; however, in the United States, tbo-filgrastim (Granix) is registered under the original biological application and is not approved for stem cell mobilization. In retrospective studies, stem cell mobilization with tbo-filgrastim has shown similar efficacy and toxicity as filgrastim, but no prospective studies have been published to date. We have conducted the first prospective randomized trial comparing the safety and efficacy of tbo-filgrastim in combination with plerixafor with that of filgrastim in combination with plerixafor for stem cell mobilization in patients with MM and NHL. This is a phase 2 prospective randomized (1:1) open-label single-institution noninferiority study of tbo-filgrastim and filgrastim with plerixafor in patients with MM or NHL undergoing auto-HSCT. Here 10 µg/kg/day of tbo-filgrastim/filgrastim was administered s.c. for 5 days (days 1 to 5). On day 4 at approximately 1800 hours, 0.24 mg/kg of plerixafor was administered s.c. Apheresis was performed on day 5 with a target cumulative collection goal of at least 5.0 × 106 CD34+ cells/kg. The primary objective was to compare day 5 CD34+ cells/kg collected. Secondary objectives included other mobilization endpoints, safety, engraftment outcomes, and hospital readmission rate. A total of 97 evaluable patients were enrolled (tbo-filgrastim, n = 46; filgrastim, n = 51). Tbo-filgrastim was not inferior to filgrastim in terms of day 5 CD34+ cell collection (mean, 11.6 ± 6.7 CD34+ cells/kg versus 10.0 ± 6.8 CD34+ cells/kg. Multivariate analysis revealed a trend toward increased mobilization in the tbo-filgrastim arm, but this was not statistically significant. The tbo-filgrastim and filgrastim arms were similar in all secondary endpoints. Tbo-filgrastim is not inferior in efficacy and has similar safety compared to reference filgrastim when used for stem cell mobilization in patients with MM and NHL. Granix can be safely used instead of Neupogen for stem cell collection in patients undergoing auto-HSCT for MM or NHL.The study is registered at https://clinicaltrials.gov/ct2/show/NCT02098109.

Single Dose Preemptive Plerixafor for Stem Cell Mobilization for ASCT After Lenalidomide Based Therapy in Multiple Myeloma: Impact in Resource Limited Setting.

Peripheral blood stem cell mobilization with cytokines for autologous stem cell transplant in multiple myeloma is adversely affected by initial induction therapy consisting of either Lenalidomide or cytotoxic drugs, with failure rates of up to 45%. The use of Plerixafor with G-CSF for PBSC mobilisation significantly improves the chances of a successful mobilization. Plerixafor is a costly therapy and increases the overall costs of ASCT which can affect the number of patients being taken up for ASCT in resource limited settings. We prospectively studied the impact of single dose preemptive Plerixafor for PBSC mobilization in patients with prior Lenalidomide exposure. 26 patients who had received Lenalidomide based induction protocol underwent PBSC mobilisation during the study period with G-CSF 10μg/kg/day SC for 4days and single dose preemptive Plerixafor 240μg/kg SC stat 11h before the scheduled PB stem cell harvest on D5, based on a D4PB CD34+ counts of <20/μL. A median of 07 cycles of Lenalidomide based combination therapy was used for induction therapy prior to ASCT. 84% patients underwent successful mobilization with one sitting of stem cell harvest post a single dose of Inj Plerixafor. 7.6% patients failed to mobilise the predefined minimum cell dose of CD34 and could not be taken up for ASCT. The median CD34% of the harvest bag sample was 0.33% (0.1-0.97%). Injection site erythema (34%), paresthesia's (34%) and nausea (30%) were the commonest adverse events reported post Inj Plerixafor. We did a real-world cost analysis for a resource limited setting for PBSC mobilization and found significant cost savings for the preemptive Plerixafor group.

Safety and Efficacy of Plerixafor on a Convenient Dose Schedule to Facilitate Outpatient Hematopoietic Stem Cell Collection for Autologous Hematopoietic Transplantation

BackgroundPlerixafor and granulocyte-colony stimulating factor (G-CSF) are commonly used in combination to mobilize CD34+ cells for collection for autologous hematopoietic stem cell transplantation (HSCT). Standard protocol involves four consecutive days of G-CSF followed by plerixafor, administered 11 hours before apheresis (for 8 am harvest next day, 9 pm administration the night before harvest). However, this timing is often logistically impractical for both patients and staff members. To examine whether plerixafor could be given on a less stringent timeline without compromising efficacy, we conducted a retrospective review of multiple myeloma patients who underwent mobilization and collection at our institution from 2010 to 2013. A further subset analysis was also performed on patients based on patient comorbidities such as age, BMI, and prior treatment with Lenalidomide to assess whether or not the earlier administration of plerixafor would affect cell collections in patients with differing characteristics.Methods52 consecutive patients with multiple myeloma at the University of Arizona Cancer Center were studied to analyze the effectiveness of G-CSF/Plerixafor mobilization with plerixafor given at approximately 14 to 17 hours before apheresis instead of 11 hours as instructed by plerixafor package insert. G-CSF was given according to standard protocol, with patients receiving a rounded dose of 10mcg/kg, to either 300 or 480mcg daily, at 0800 for four consecutive days. Plerixafor was given on the 4th day at 14 to 17 hours (2-5 PM instead of 9PM) before apheresis, which commenced at 0800 the following morning. Patients were given additional doses of plerixafor if inadequate numbers of cells were collected in the initial apheresis session.ResultsThe patient population consisted of 52 consecutive patients, aged 36 to 77 years old, with BMIs ranged 18.7 to 46.6, of which 28 had previously been treated with Lenalidomide. The median number of apheresis sessions to reach goal CD34+ count of 2 X 10^6 was 1 (range 1-4). 11 patients required 2 or more collections (6 patients required 2 collections, 4 required 3, and one individual required 4 collections). Mean CD34+ count collected after all required apheresis sessions per patient was 9.74 x 10^6 (range 2.07 x 10^6 - 24.99 x 10^6). All patients collected sufficient stem cells to proceed with autologous HSCT. Patient were then divided into further groups for further analysis: age (62 or less vs greater than 62), BMI (less than 28 vs 28 or greater), and lenalidomide treatment in the past. None of those three characteristics showed any statistical difference in the number of CD34+ stem cells collected (See graph 1, 2, and 3).ConclusionBased on these data, plerixafor mobilization remains an effective method of stem cell mobilization despite lengthening of the interval from medication administration to apheresis. Moreover, this alleviates the major logistical disadvantage of using plerixafor for stem cell mobilization. [Display omitted] [Display omitted] [Display omitted] DisclosuresMcBride:Sanofi: Research Funding.

Plerixafor for Stem Cell Mobilization in Allogeneic Stem Cell Donors

Plerixafor for Stem Cell Mobilization in Allogeneic Stem Cell Donors

Autologous Stem Cell Mobilization in AL Amyloidosis with Plerixafor and G-CSF: Update of a Single Center Experience

Standard initial therapy for a minority of patients with systemic AL amyloidosis is risk-adapted melphalan and stem cell transplant (SCT) with SC mobilization often accomplished with high dose G-CSF (16μg/kg/d). Based on the phase III experience in MM, we investigated the combination of G-CSF and Plerixafor for stem cell mobilization in AL. We report an update of our experience with this mobilization approach. Patients were diagnosed by standard criteria with tissue biopsies showing amyloidosis. They were mobilized and collected between 4/16/12 and 9/11/13 with G-CSF 10μg/kg/d subcutaneously (SC) for 5 days (and continued through collection) and Plerixafor, adjusted for renal function, starting on day 4 until collection was completed. We report on 12 patients whose median age at mobilization was 58 yrs (range 46-72), 58% of whom were men. Median number of organs involved was 2 (range 1-4), most frequently the kidneys (n=9) and the heart (n=8). Median time from diagnosis to mobilization was 7.5 mths (range 2-123). 9 patients had prior bortezomib-based therapy with a median of 3 cycles (range 0-6). One had received a SCT 10 years prior and relapsed, and one was 1 yr s/p orthotopic heart transplant. 5 patients had a creatinine of ≥ 1.5 mg/dL including 2 on hemodialysis. The target CD34+ cell dose was 10 x 106 CD34/kg for all but one patient due to the history of prior SCT. The median number of collections was 2 (range 2-3). On day one, a median of 3.6 x106 CD34/kg (0.4-13.8x106) was collected and on day two, 6.4 x106 (2.7-19x106). The median total CD34+ cells collected per kg was 13.8x106 (5-18x106). No significant toxicities were observed with Plerixafor. 2 patients had grade 1 bleeding from the catheter site during apheresis and one had dyspnea with suspected fluid overload which responded to furosemide. All patients went on to receive high dose chemotherapy with melphalan followed by autologous SCT. The median stem cell dose infused was 7.7x 106 CD34/kg and median days to ANC > 500 was 11 (10-22), to platelets > 20K untransfused was 22 (15-44) and to lymphocytes > 500/μl was 14.5 (11-25). One patient who had VOD and persistent thrombocytopenia was given the remainder of his stem cells on day +31 due with subsequent normalization of his CBC. Mobilization with G-CSF and Plerixafor was well tolerated in AL patients with multiple organs involved. Limited leukaphereses were needed to achieve or exceed the target CD34+ cell dose. In the era of more effective initial therapies, an era in which many AL patients are living longer with moderate to severe organ damage and receiving multiple lines of therapy including SCT, this approach allows not only the collection of sufficient CD34+ cells for optimal immediate stem cell dosing, but also the cryopreservation of aliquots for future transplants should they become necessary and for novel cell-based therapies should they become available.

Phase 2 trial of intravenously administered plerixafor for stem cell mobilization in patients with multiple myeloma following lenalidomide-based initial therapy

Initial therapy of multiple myeloma with lenalidomide-based regimens can compromise stem cell collection, which can be overcome with the addition of plerixafor. Plerixafor is typically given subcutaneously (SQ), with collection approximately 11 hours later for maximum yield. Intravenous (IV) administration may allow more rapid and predictable mobilization. This trial was designed to assess the efficacy and feasibility of IV plerixafor in patients receiving initial therapy with a lenalidomide-based regimen. Patients received G-CSF at 10 μg/kg/day for 4 days followed by IV plerixafor at 0.24 mg/kg/dose starting on day 5; plerixafor administered early in the morning with apheresis 4–5 hours later. Thirty-eight (97%) patients collected at least 3×106 CD34+ cells/kg within 2 days of apheresis. The median CD34+ cells/kg after 1 day of collection was 3.9×106 (range; 0.7–9.2) and after two days of collection was 6.99×106 (range: 1.1–16.5). There were no grade 3 or 4 non-hematological adverse events and one patient experienced grade 4 thrombocytopenia. The most common adverse events were nausea, diarrhea and abdominal bloating. IV plerixafor is an effective strategy for mobilization with low failure rate and is well tolerated. It offers flexibility with a schedule of early morning infusion followed by apheresis later in the day.

PCN88 Cost-Effectiveness Analysis of Plerixafor for Stem Cell Mobilization for Poor Mobilizers in Canada

PCN88 Cost-Effectiveness Analysis of Plerixafor for Stem Cell Mobilization for Poor Mobilizers in Canada

Despite the Use of the Combination of G-CSF and Plerixafor for Stem Cell Mobilization, One Third of the Patients with Lymphoma Were Still “Poor Mobilizer” Using the Criteria Recently Proposed by GITMO (< 2.0 X 10 6 CD 34 + Cells Per Kg in ≤ 3 Apheresis)

Despite the Use of the Combination of G-CSF and Plerixafor for Stem Cell Mobilization, One Third of the Patients with Lymphoma Were Still “Poor Mobilizer” Using the Criteria Recently Proposed by GITMO (< 2.0 X 10 6 CD 34 + Cells Per Kg in ≤ 3 Apheresis)

Efficacy of Plerixafor Administered At 5:00PM for Stem Cell Mobilization in Lymphoma and Myeloma Patients Undergoing Autologous Stem Cell Transplant,

Abstract 4061 Background:High-dose chemotherapy and/or radiotherapy are effective treatment strategies for patients with life-threatening hematologic malignancies. A critical step to the success of transplantation is achieving adequate mobilization of CD34+ stem cells from the bone marrow into the peripheral blood to provide sufficient cell yield after apheresis for the transplant. Plerixafor combined with granulocyte colony-stimulating factor (G-CSF) has proven efficacious in mobilizing CD34+ stem cells in patients with lymphoma and myeloma prior to autologous stem cell transplantation. In the phase 3 clinical trials of plerixafor plus G-CSF for SCM, plerixafor was administered at 10:00 pm on days prior to apheresis. This dosing schedule is based on the peak level of CD34+ cells in the peripheral blood (PB) at 11–14 hours after administration; however PB CD34+ cell levels were elevated from 4–18 hours after plerixafor administration. Due to inconvenience in dosing plerixafor at 10:00pm, we took advantage of its pharmacodynamic profile and explored an alternative dosing schedule, giving plerixafor at 5:00 pm. Here, we report our updated experience with the efficacy of this schedule. Method:We performed a retrospective study using our Stem Cell Harvest database. A total of 58 patients (31 lymphoma, 27 myeloma) underwent mobilization with G-CSF + plerixafor, either as front-line (n=51) or as salvage (n=7) mobilization strategies between February 2009 through May 2010. Mobilization consisted of G-CSF 10 μg/kg SC administered daily at 6:00 am day 1 through 4 plus plerixafor 0.24 mg/kg SC given once daily at 5:00 pm in an outpatient clinic beginning on day 4. For patients with renal impairment (ie, creatinine clearance ≤50 mL/min), the dose of plerixafor was lowered by a third to 0.16 mg/kg. Daily apheresis began at 8:30 am on the morning of day 5 and continued for up to 4 days, with a minimum collection goal defined as ≥ 2 × 106 CD34+ cells/kg for lymphoma patients and ≥ 4 × 106 CD34+ cells/kg for myeloma patients. Mobilization with G-CSF plus plerixafor and apheresis were halted once the minimum goal was reached between day 2 and 4 of apheresis, or after a single collection achieved the optimal goal which was defined as ≥ 4 × 106 (lymphoma) or ≥ 8 × 106 (myeloma) CD34+ cells/kg. The mobilization strategy was considered a failure if patients did not reach the minimum CD34+ cell collection goal within the 4 days of apheresis. Results:G-CSF + plerixafor mobilization yielded a median 5.13 × 106 CD34+ cells/kg (range, 0.06–25.8) in a median of 2 apheresis days. Forty-five of 58 (78%) patients achieved the minimum CD34+ cells/kg required for transplantation, including 30 (52%) patients who achieved this goal on the first day of apheresis. Overall, 52 (90%) patients proceeded to transplantation, with median neutrophil and platelet engraftment times of 11 and 18 days, respectively. Conclusion:In summary, the alternative 5:00 pm dosing of plerixafor for stem cell mobilization provided a more convenient dosing schedule while ensuring that a majority of lymphoma and myeloma patients achieved the minimum CD34+ cell yield required to proceed to transplantation. Disclosures:Tornatta:Genzyme: Consultancy, Honoraria, Speakers Bureau. Fung:Genzyme: Consultancy, Honoraria, Speakers Bureau.

Late Afternoon Dosing of Plerixafor for Stem Cell Mobilization: A Practical Solution

Plerixafor was recently approved for stem cell mobilization in patients who have non-Hodgkin lymphoma or multiple myeloma. However, the use of late evening (10 PM) injections is inconvenient for patients and requires an after-hours infrastructure that may not be readily available. Based on an earlier study showing prolonged mobilization of stem cells in patients given plerixafor plus granulocyte colony-stimulating factor (G-CSF), we administered plerixafor at 5 PM and performed apheresis approximately 15 hours later. Plerixafor was administered primarily to patients who either had failed previous mobilization or were at risk for poor mobilization because of previous therapy, especially lenalidomide in patients who had multiple myeloma. Of 48 patients, including 24 with myeloma and 24 with lymphoma, 47 had enough stem cells collected (> 2 × 10E6 CD34+ cells/kg) to proceed to transplant, including all 13 patients who had failed previous chemotherapy plus G-CSF mobilization and 18 patients treated with four cycles or more of lenalidomide. The day +1 post-plerixafor increment in circulating CD34+ cells was greatest in patients who had the highest preplerixafor CD34 count; however, in patients with preplerixafor CD34+ cell counts < 10/μL (and who typically mobilize poorly), 83% of patients had enough stem cells collected to proceed to transplant. This study suggests that plerixafor is effective when given 15 hours before apheresis, even in a population at high risk for mobilization failure. A proposed cost-effective use of plerixafor is to administer it to patients who are inadequately mobilized with G-CSF alone or for salvage in patients who fail previous mobilization with chemotherapy plus G-CSF.

A Risk Adapted Approach Utilizing Plerixafor In Autologous Peripheral Blood Stem Cell Mobilization

Many patients (pts) who are eligible for ASCT are unable to collect a minimum number of CD34 + stem cells to support high dose chemotherapy and ASCT. Plerixafor, a CXCR4 antagonist, in combination with G-CSF mobilizes more CD34+ stem cells when compared to G-CSF alone. Due to its cost, we commenced a risk adapted approach to the utilization of plerixafor for stem cell mobilization in pts undergoing ASCT. Our goal was to add plerixafor in pts who had ineffective mobilization thereby preventing mobilization failures.

Plerixafor for Stem Cell Mobilization in Patients with Non-Hodgkin's Lymphoma and Multiple Myeloma

To evaluate the literature characterizing the mechanism of action, pharmacokinetics, pharmacodynamics, and therapeutic efficacy of plerixafor for hematopoietic stem cell (HSC) mobilization for autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) or multiple myeloma. A PubMed search (1966-September 2009) was conducted using the key words plerixafor and AMD3100. Manufacturer's prescribing information was also used. English-language articles were selected and data were extracted with a focus on clinical studies of HSC mobilization in patients with NHL or multiple myeloma. Plerixafor exerts its effect by reversibly blocking the ability of HSC to bind to the bone marrow matrix. When used with granulocyte colony-stimulating factor (G-CSF), plerixafor helps increase the number of HSCs in the peripheral blood, where they can be collected for use in autologous transplantation. In clinical studies, plerixafor was rapidly absorbed after subcutaneous injection, reaching a maximum plasma concentration at approximately 0.5 hours. Plerixafor is renally excreted as the parent drug, with an elimination half-life ranging from 3 to 5 hours. Plerixafor increases circulating CD34+ cells in the peripheral blood, with a peak effect about 6-9 hours after subcutaneous administration. An approximate 2- to 3-fold increase in the CD34+ cell count is seen by the first dose of plerixafor after 4 consecutive days of G-CSF treatment. In 2 Phase 3 studies in patients with NHL or multiple myeloma, addition of plerixafor to G-CSF resulted in a higher CD34+ cell collection with fewer apheresis days, but failed to show better graft durability or overall patient survival for up to 12 months of follow-up. Clinical trials have demonstrated that the addition of plerixafor to G-CSF was beneficial for HSC mobilization to peripheral blood for collection and subsequent transplantation in patients with NHL or multiple myeloma. Further studies should assess the benefit of the additive use of plerixafor on clinical outcomes.

Safety and efficacy assessment of plerixafor in patients with multiple myeloma proven or predicted to be poor mobilizers, including assessment of tumor cell mobilization

This was an open-label, single-center, phase II study of 20 patients with multiple myeloma who were either proven poor mobilizers (n=10; group A) or predicted poor mobilizers (n=10; group B) and were planned for autologous hematopoietic SCT. The aim was to assess the safety and efficacy of plerixafor for stem cell mobilization and tumor cell contamination. The peripheral blood (PB) CD34+ cell count was generally very low pre- plerixafor and increased significantly post-plerixafor administration. Cumulative apheresis yields of > or =2 x 10(6) CD34+ cells/kg were observed in 7 of 10 patients (group A) and 8 of 10 patients (group B). Among the proven poor mobilizers, there was no evidence of tumor cell mobilization in the PB after G-CSF plus plerixafor treatment. Seventeen of 20 (85%) patients underwent transplantation. Neutrophil engraftment occurred at a median of 13 days for all patients. Platelet engraftment occurred at a median of 16 days and 19 days for all proven and predicted poor mobilizers, respectively. At 12 months, 12 of 17 patients had documented durable grafts, 3 of 17 patients died and 2 of 17 patients were lost to follow-up; but they had documented graft durability at the previous 3- and 6-month visit. The safety profile of plerixafor in all patients was consistent with previous reports.