Upfront Plerixafor Research Articles

Anti-CD38 monoclonal antibody impairs CD34+ mobilization and affects clonogenic potential in multiple myeloma patients.

Induction with daratumumab-based regimens followed by autologous stem cell transplantation is the current standard for newly diagnosed multiple myeloma (NDMM) patients eligible for intensive chemotherapy. However, concerns emerged regarding potential negative effects following daratumumab-based treatment on CD34+ mobilization. We here compared CD34+ mobilization and clonogenic potential between daratumumab and non-daratumumab based therapy without upfront plerixafor administration among patients affected by NDMM. Clinical, mobilization and clonogenic data from 41 consecutively enrolled NDMM patients were analyzed. Patients underwent collection of autologous CD34+ by apheresis at the ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, from January 2021 to March 2023. Clonogenicity analysis was performed on BFU-E and CFU-GM. Seventy-five percent of daratumumab-treated patients underwent >1 apheresis, compared to 24% of non-daratumumab patients (p=0.0017). Daratumumab-treated patients had significantly lower CD34+ count (mean 38 vs 79/μL, respectively; p=0.0011), with a median CD34+ harvest of 3.98×106/kg (range 1.68-9.18) vs 6.87×106/kg (range 1.63-16.85) in non-daratumumab-treated (p=0.0006). In multivariate analysis the likelihood of undergoing >1 apheresis was significantly higher in older patients (OR 1.2, 95% CI 1-1.4, Z=2.10, p=0.03) and daratumumab-treated patients (OR 15, 95% CI 2.8-129, p=0.004). Moreover, daratumumab-based induction therapy demonstrated an independent negative association with BFU-E colony formation (p=0.0148), even when accounting for patient age and CD34+ levels. Our findings underscore the impact of daratumumab-based treatment on CD34+ mobilization in a real-life, upfront plerixafor-free population of NDMM patients. Higher probability of requiring multiple apheresis occurred among daratumumab-treated patients. Interestingly, the observation that daratumumab might negatively impact BFU-E colony formation, independent of CD34+ cell count, offers novel biological perspectives. Appropriate strategies should be adopted by the Apheresis teams to mitigate these potential negative effects.

Outcomes of upfront plerixafor use for mobilization in germ cell tumor patients

High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improved 5-year overall survival rates in relapsed/refractory germ cell tumors (GCTs) from 10% to 52%. Nearly 30% of GCT patients are deemed poor mobilizers after receiving several lines of prior therapy. There is limited data available regarding upfront plerixafor use in GCT patients. We predicted upfront plerixafor use would increase the amount of stem cells collected preventing subsequent mobilizations and improve time to curative therapy. A retrospective, single center, chart review of adult GCT patients who received plerixafor upfront for mobilization at a single center between January 1, 2013 and August 31, 2021 was performed.The primary objective was to evaluate the rate of successful peripheral blood CD34+ cell collections. Secondary objectives consisted of describing the impact of plerixafor use on mobilization and assessing auto-HSCT related outcomes. Sixteen patients received plerixafor upfront after an average of three prior lines of therapy (range: 2-5 lines). Successful collection (≥4 × 106 CD34+ cells/Kg collected within four days) was achieved in 15 (94%) patients in a median of one apheresis day (interquartile range: 1-2 days). All patients proceeded to an initial auto-HSCT and 12 patients (75%) completed both transplants as planned. Survival at 12 months was 50%.The significantly higher amount of CD34+ cells collected over less apheresis days demonstrated the clinical utility of upfront plerixafor and its potential to facilitate more efficient stem cell mobilization. There is a need for larger randomized studies with upfront plerixafor use in this unique patient population.

Stem Cell Mobilization Yields with Daratumumab- and Lenalidomide-Containing Quadruplet Induction Therapy in Newly Diagnosed Multiple Myeloma: Findings from the MASTER and GRIFFIN Trials

For eligible patients with newly diagnosed multiple myeloma (NDMM), standard of care includes induction therapy followed by autologous stem cell transplantation (ASCT). Daratumumab as monotherapy and in combination treatment is approved across multiple lines of therapy for multiple myeloma (MM), and lenalidomide is an effective and commonly used agent for induction and maintenance therapy in MM. However, there is concern that lenalidomide and daratumumab given as induction therapy might impair mobilization of stem cells for ASCT. Therefore, we assessed stem cell mobilization in patients following frontline induction therapy in the MASTER and GRIFFIN phase 2 clinical studies by examining stem cell mobilization yields, apheresis attempts, and engraftment outcomes for patients from each study. Adult transplantation-eligible patients with NDMM received induction therapy consisting of daratumumab plus carfilzomib/lenalidomide/dexamethasone (D-KRd) for four 28-day cycles in the single-arm MASTER trial or lenalidomide/bortezomib/dexamethasone (RVd) with or without daratumumab (D) for four 21-day cycles in the randomized GRIFFIN trial, followed by stem cell mobilization and ASCT in both studies. Institutional practice differed regarding plerixafor use for stem cell mobilization; the strategies were upfront (ie, planned plerixafor use) or rescue (ie, plerixafor use only after mobilization parameters indicated failure with granulocyte colony-stimulating factor [G-CSF] alone). Descriptive analyses were used to summarize patient characteristics, stem cell mobilization yields, and engraftment outcomes. In MASTER, 116 D-KRd recipients underwent stem cell mobilization and collection at a median of 24 days after completing induction therapy. In GRIFFIN, 175 patients (D-RVd, n=95; RVd, n=80) underwent mobilization at a median of 27 days after completing D-RVd induction therapy and 24 days after completing RVd induction therapy. Among those who underwent mobilization and collection, 7% (8 of 116) of D-KRd recipients, 2% (2 of 95) of D-RVd recipients, and 6% (5 of 80) of RVd recipients did not meet the center-specific minimally required CD34+cell yield in the first mobilization attempt; however, nearly all collected sufficient stem cells for ASCT on remobilization. Among patients who underwent mobilization, plerixafor use, either upfront or as a rescue strategy, was higher in patients receiving D-KRd (97%; 112 of 116) and D-RVd (72%; 68 of 95) compared with those receiving RVd (55%; 44 of 80). The median total CD34+cell collection was 6.0×106/kg (range, 2.2 to 13.9×106/kg) after D-KRd induction, 8.3×106/kg (range, 2.6 to 33.0×106/kg) after D-RVd induction, and 9.4×106/kg (range, 4.1 to 28.7×106/kg) after RVd induction; the median days for collection were 2, 2, and 1, respectively. Among patients who underwent mobilization, 98% (114 of 116) of D-KRd patients, 99% (94 of 95) of D-RVd patients, and 98% (78 of 80) of RVd patients underwent ASCT using median CD34+cell doses of 3.2×106/kg, 4.2×106/kg, and 4.8×106/kg, respectively. The median time to neutrophil recovery was 12 days in all 3 treatment groups across the 2 trials.Because both trials used different criteria to define platelet recovery, data on platelet engraftment using the same criteria are not available. Four cycles of daratumumab- and lenalidomide-based quadruplet induction therapy had a minimal impact on stem cell mobilization and allowed predictable stem cell harvesting and engraftment in all patients who underwent ASCT. Upfront plerixafor strategy may be considered, but many patients were successfully collected with the use of G-CSF alone or rescue plerixafor.

Despite Use of Upfront Plerixafor and G-CSF, Daratumumab Exposure Reduces Stem Cell Mobilization in Patients with Multiple Myeloma

Introduction Daratumumab is an anti-CD38 IgG1k monoclonal antibody with direct tumor killing and immunomodulatory mechanisms of action which was shown to have clinical benefits when added to the standard-of-care induction regimen in transplant eligible multiple myeloma (MM) patients. However, prior studies have indicated a potential reduction in stem cell yield in patients exposed to daratumumab prior to stem cell mobilization. Additionally, prior studies have not utilized combination mobilization regimens with G-CSF and the CXCR4 antagonist plerixafor as standard-of-care, which may overcome the deleterious effect of daratumumab. In this study, we investigated the stem cell yield of plerixafor-treated patients with daratumumab exposure compared to those without. Methods We conducted a retrospective study of patients with MM at our institution who underwent autologous stem cell mobilization and collection during first-line treatment over a 15-month period from 2021-2022. Following induction, patients underwent mobilization with a regimen of G-CSF for 5 days with plerixafor on the 4th day. Circulating CD34+ stem cells were enumerated on the 5th day, after which patients underwent approximately 20L apheresis with a collection goal of 5x106 CD34+ cells/kg of body weight. The primary endpoint of this study was the comparison of circulating CD34+ cells between patients who received daratumumab during induction and those who did not. Secondary endpoints included collection CD34+ yield and proportion who met the collection goal. Results 123 patients were included in the analysis. The median age was 65 (range: 34-77), 54% were male, and 84% were White. Twenty-two percent were stage I, 58% stage II, and 19% stage III by the Revised International Staging System. Forty-seven percent received daratumumab during induction. Of those, the median number of cycles administered was 4 (range: 1-5). Ninety percent received daratumumab in combination with bortezomib, lenalidomide and dexamethasone. The two cohorts were balanced in terms of age, gender, race, and exposure to lenalidomide, alkylators and radiation during induction. Patients with daratumumab exposure had a mean mobilization of 57.5 CD34+ cells/mcl compared to 96.4 for those without (p < 0.001). The mean CD34+ cell collection yield in 1 apheresis procedure was 6.0 x 106 cells/kg compared to 10.6 x 106 cells/kg (p < 0.001). Fifty-three percent of patients with daratumumab exposure met the collection goal compared to 80% of patients without (p < 0.001). Of the patients who did not meet the goal in one apheresis procedure, the majority were able to meet the goal with 1-3 additional days of apheresis (Figure 1). However, only 86% of patients with daratumumab exposure met the collection goal compared to 97% of those without (p < 0.001). Ten patients failed to collect 2.0 x 106 cells/kg, the institutional minimum for transplantation, 9 of which received daratumumab during induction. Eight were able to collect the minimum with an additional 1-3 days of apheresis; 2 patients required an additional mobilization procedure and collection but were able to proceed to transplantation. After adjusting for covariates including age, gender, race, weight, and exposure to lenalidomide, alkylators, and radiation, daratumumab exposure was associated with a 37.9 cells/mcl decrease in mean mobilization of CD34+ and 4.2 x 106 cells/kg decrease in CD34+ cell collection (both p < 0.001). Alkylator exposure was associated with a 43.3 cells/mcl decrease in mean mobilization of CD34+ (p = 0.040) and 4.1 x 106 cells/kg decrease in CD34+ cell collection (p = 0.057). Lenalidomide exposure was associated with a 103.4 cells/mcl decrease in mean mobilization of CD34+ (p <0.001) and 8.7 x 106 cells/kg decrease in CD34+ cell collection (p <0.001). Conclusion Inclusion of daratumumab in the induction regimen for transplant-eligible patients with MM resulted in a significant reduction in stem cell mobilization and stem cell yield, even with the use of plerixafor-containing mobilization regimens. This reduction was similar to alkylator exposure but less than lenalidomide exposure. With the increasing use of quadruplet induction regimens, the frequency of mobilization failure is likely to increase in the future and new mobilization regimens and approaches are needed to guarantee adequate cell yields without the need for additional days of apheresis and/or mobilizations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Stem Cell Collection with Daratumumab (DARA)-Based Regimens in Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (pts) in the Griffin and Master Studies

Stem Cell Collection with Daratumumab (DARA)-Based Regimens in Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (pts) in the Griffin and Master Studies

Pre-transplant myeloid and immune suppression, upfront plerixafor mobilization and post-transplant cyclophosphamide: novel strategy for haploidentical transplant in sickle cell disease.

Allogenic hematopoietic stem cell transplant is the only curative option for symptomatic sickle cell disease (SCD). HLA haploidentical related donor transplants are associated with high graft failure rates. We conceptualized a novel protocol (APOLLO protocol) using pre-transplant immune and myelosuppression (PTIS) using fludarabine, cyclophosphamide, and dexamethasone followed by augmented John Hopkins protocol by adding thiotepa to conditioning. Twenty-five consecutive patients suffering from symptomatic SCD were enrolled into the study. We added upfront plerixafor to granulocyte colony stimulating factor (GCSF) for mobilization of healthy donors. Graft versus host disease (GvHD) prophylaxis was done using post-transplant cyclophosphamide, sirolimus, and mycophenolate mofetil. Graft failure was not seen in any of our patients. Five patients developed acute grade II/IV GvHD (4 classical acute, 1 late onset), 3 had limited chronic GvHD. Out of 25 evaluable patients, 22 are alive and disease free, making an overall survival (OS) and disease-free survival (DFS) of 88% with a median follow up of 485 days (range 198-802). T-cell-replete haploidentical transplant with PTIS, augmented John Hopkins conditioning and plerixafor based mobilization is a safe and effective way of treating patients suffering from SCD with minimal or no risk of graft failure and acceptable GvHD rates.

Preemptive and Upfront Plerixafor: Safe and Effective Strategy for Patients Undergoing Autologous Stem Cell transplant and at High Risk for Mobilization Failure

Abstract Introduction: Approximately 10%–30% of patients are unable to collect the minimum number of stem cells to support high-dose chemotherapy and autologous stem cell transplant (hematopoietic stem cell transplantation). Plerixafor alone or in combination with granulocyte colony-stimulating factor (G-CSF) has been shown to significantly increase the CD34 cell collection, especially in patients who failed their initial harvest strategy. This is a retrospective study of 17 preselected patients (relapsed lymphoma and myeloma), who were considered to have high risk of mobilization failure and who had undergone upfront and preemptive plerixafor mobilization. Patients and Methods: The mobilization protocol consisted of G-CSF (10–15 μg/kg) subcutaneously daily for 4 days before the initiation of plerixafor on evening of day 4. The patients then underwent apheresis on day 5. Results: Among 17 patients who underwent apheresis, 16 (93%) yielded the minimum required cell collection of ≥2 × 106 CD34+ cells/kg in a single apheresis session (2 days). Out of these 16 patients, 8 (53%) patients achieved the minimum target dose in a single day. Eight (50%) of all patients achieved the optimum target cell collection in a single apheresis session. Out of these eight patients, five (62%) patients collected optimum yield in a single day. Conclusion: Plerixafor is safe and effective if used upfront and preemptively for patients in whom mobilization of stem cells is considered to be a problem.

Mobilization of Hematopoietic Progenitor Cells for Autologous Transplantation Using Pegfilgrastim and Plerixafor: Efficacy and Cost Implications

Filgrastim (FIL) is the most common growth factor combined with plerixafor for autologous hematopoietic progenitor cell mobilization, but requires daily, multi-injection administration. We adopted a standardized mobilization regimen with pegfilgrastim (PEG) and upfront plerixafor, allowing for a single injection given the long half-life and slow elimination of PEG. Between 2015 and 2017, a total of 235 patients with lymphoma or plasma cell dyscrasias underwent mobilization with PEG 6 mg on day 1 and upfront plerixafor 24 mg on day 3, followed by apheresis on day 4 regardless of peripheral blood CD34+ cells. The median CD34+ cells/mm3 in peripheral blood on first day of collection was 48 and median collection yield was 7.27 × 106 CD34+ cells/kg (range, 0.32 to 39.6 × 106 CD34+ cells/kg) after a mean of 1.6 apheresis collections. Overall, 83% of patients achieved the mobilization target, and 95% reached the minimum necessary CD34+ cell yield to proceed with transplantation (2 × 106 CD34+ cells/kg). Because FIL is weight-based and dosed daily, the cost comparison with PEG is influenced by patient weight and number of apheresis sessions required. A cost simulation using actual patient data indicates that PEG is associated with lower cost than FIL for the majority of patients. Autologous hematopoietic progenitor cell mobilization with PEG and plerixafor is practical, effective, and not associated with increased cost compared with FIL mobilization.

Predicting failure of hematopoietic stem cell mobilization before it starts: the predicted poor mobilizer (pPM) score

Predicting mobilization failure before it starts may enable patient-tailored strategies. Although consensus criteria for predicted PM (pPM) are available, their predictive performance has never been measured on real data. We retrospectively collected and analyzed 1318 mobilization procedures performed for MM and lymphoma patients in the plerixafor era. In our sample, 180/1318 (13.7%) were PM. The score resulting from published pPM criteria had sufficient performance for predicting PM, as measured by AUC (0.67, 95%CI: 0.63-0.72). We developed a new prediction model from multivariate analysis whose score (pPM-score) resulted in better AUC (0.80, 95%CI: 0.76-0.84, p < 0001). pPM-score included as risk factors: increasing age, diagnosis of NHL, positive bone marrow biopsy or cytopenias before mobilization, previous mobilization failure, priming strategy with G-CSF alone, or without upfront plerixafor. A simplified version of pPM-score was categorized using a cut-off to maximize positive likelihood ratio (15.7, 95%CI: 9.9-24.8); specificity was 98% (95%CI: 97-98.7%), sensitivity 31.7% (95%CI: 24.9-39%); positive predictive value in our sample was 71.3% (95%CI: 60-80.8%). Simplified pPM-score can "rule in" patients at very high risk for PM before starting mobilization, allowing changes in clinical management, such as choice of alternative priming strategies, to avoid highly likely mobilization failure.

Outcomes of G-CSF alone vs G-CSF with upfront plerixafor vs G-CSF/chemotherapy for collection of autologous stem cells in patients with multiple myeloma.

e19504 Background: Strategies for optimizing the collection of peripheral blood stem cells (PBSC) for autologous stem cell transplant (ASCT) in patients with multiple myeloma (MM) vary among transplant centers, and include the use of G-CSF alone or in combination with plerixafor, or mobilization chemotherapy + G-CSF. In 2010, we started using “upfront” plerixafor, given on the day before the PBSC collection. Methods:We retrospectively analyzed the outcomes of 423 consecutive MM patients who underwent PBSC collections at the Penn State Hershey Cancer Institute. PBSC were collected after mobilization chemotherapy + G-CSF 5 mcg/Kg/day (group A, 91 pts), G-CSF alone, 10-16 mcg/Kg/day (group B, 72 pts), and G-CSF with “upfront” plerixafor 0.16-0.24 mg/Kg on the day before the stem cell collection (group C, 245 pts). Fifteen patients were excluded from the analysis because they collected with chemotherapy + plerixafor, received pegylated G-CSF, or plerixafor “on demand”, i.e., after failure to achieve an adequate number of stem cells on the first day of collection. We compared yields, number of days required for apheresis, clinical outcomes, and adverse events among these groups. Results: The median number of PBSC collected was 16.4 (range, 0.1-134), 4.2 (range, 0-12), and 6.2 (range, 0.2-41.2) million CD34+ cells/Kg in group A, B, and C, respectively (p&lt;0.001). The mean number of days to collect PBSC was 1.5, 1.5, and 1.3 in group A, B, and C, respectively (p=0.033). Collection failure, defined as a yield &lt;2 million CD34+cells/Kg, was observed in 5 (5.5%), 9 (12.5%), and 15 (6.1%) patients of group A, B, and C, respectively (p&lt;0.001). Twenty patients in group A developed neutropenic fever requiring hospital admission, and 1 of them died of septic shock, whereas no mortality was observed in groups B or C. No difference in the rapidity of PBSC engraftment, progression-free survival, and overall survival was observed among the 3 groups. Conclusions:In patients with MM, the upfront use of plerixafor with G-CSF provided the best collection strategy: it avoided the morbidity and mortality associated with the mobilization chemotherapy, and it provided higher yields than G-CSF alone.

Hematopoietic Progenitor Cell Mobilization with Ifosfamide, Carboplatin, and Etoposide Chemotherapy versus Plerixafor-Based Strategies in Patients with Hodgkin and Non-Hodgkin Lymphoma

Studies comparing the efficacy and safety of chemo-mobilization with ifosfamide, carboplatin, and etoposide (ICE) ± rituximab with plerixafor-based approaches in lymphoma patients have not been performed. We analyzed hematopoietic progenitor cell mobilization outcomes in lymphoma patients undergoing chemo-mobilization with ICE (n = 35) compared with either routine plerixafor (n = 30) or “just in time” (JIT) plerixafor-based mobilization (n = 33). Chemo-mobilization provided a significantly higher total CD34+ cell yield (median collection, 5.35 × 106 cells/kg for ICE versus 3.15 × 106 cells/kg for routine plerixafor and 3.6 × 106 cells/kg for JIT plerixafor, P < .001). The median day 1 yield of CD34+ cells was not significantly different (median, 2.2 × 106 cells/kg in ICE versus 1.9 × 106 cells/kg in upfront plerixafor versus 1.7 × 106 cells/kg in JIT plerixafor, P = .20). There was no significant difference in the 3 groups in terms of total number of apheresis sessions performed (median, 2 in each group; P = .78). There were no mobilization failures (inability to collect at least 2 × 106 cells/kg) in the chemo-mobilization group, whereas 5 patients (16.7%) in the routine plerixafor and 3 patients (9.1%) in JIT group had mobilization failure (P = .04). Mean time to neutrophil engraftment was faster in the chemo-mobilization group, 10.3 days (±1.2) compared with 12.1 days (±3.6) in the routine plerixafor group and 11.6 days (±3.0) in the JIT group (P < .001) and mean time to platelet engraftment was 13.7 days (±.7) in ICE versus 20.3 days (±1.6) in routine plerixafor versus 17.1 days (± .9) in JIT group (P < .001). Red blood cell transfusions were significantly higher in the chemo-mobilization group (34.3% versus 0 versus 3.2% versus 1, P < .001) and so were the platelet transfusions (22.9% versus 0 versus 0, P < .001). Excluding the cost of chemotherapy administration, chemo-mobilization was associated with significantly less mobilization cost (average cost $17,601.76 in ICE versus $28,963.05 in routine and $25,679.81 in JIT, P < .001). Our data suggests that chemo-mobilization with ICE provides a higher total CD34+ cell yield, lower rates of mobilization failure, faster engraftment, and lower cost compared to plerixafor-based approaches with comparable toxicity profile between the groups, except for higher transfusion requirements with chemo-mobilization.

Stimulation of Adrenergic Activity By Desipramine Enhances Hematopoietic Stem and Progenitor Cell Mobilization Along with G-CSF in Multiple Myeloma - a Pilot Study of Safety and Efficacy

Background:Hematopoietic stem cell release is regulated by the sympathetic nervous system through the β (3) adrenergic receptor [Mendez-Ferrer et al. Nature 2008]. Peripheral sympathetic nerve neurons express the G-CSF receptor and stimulation of peripheral sympathetic nerve neurons with G-CSF reduced norepinephrine (NE) reuptake significantly, suggesting that G-CSF potentiates the sympathetic tone by increasing NE availability [Lucas et al Blood 2012]. Based on preclinical data, we investigated the NE reuptake inhibitor desipramine in HSC mobilization.Despite augmentation with Plerixafor (CXCR4 inhibitor), 20% of all patients fail to mobilize 6*10^6 CD34 cells/kg in myeloma and the collection rate with G-CSF alone is 51.1% [Diperiso et al Blood 2012]. The cost of upfront plerixafor is $9,081 per patient while desipramine costs $40. We undertook a feasibility study of adult patients with MM undergoing autologous transplantation (ASCT) to study safety and efficacy of mobilization with desipramine and G-CSF.Patients & Methods:From 2013- 2014, 10 patients between the ages of 18-70, eligible for ASCT were enrolled. Desipramine 100mg daily was administered for 7 days, starting 4 days prior to starting G-CSF (D-3) and continue along with G-CSF for a total of 7 days. CBC and CD34 counts were determined on Day+5. If CD34 counts were > 10/ul, stem cell collection was commenced and if < 10/ul, plerixafor was added as salvage therapy. The endpoints were safety and efficacy in mobilizing CD34 cells for ASCT in patients with multiple myeloma. This trial was registered at clinicaltrials.gov as NCT01899326.ResultsSix of ten patients enrolled completed the protocol and underwent stem cell transplantation. Reasons for not completing were 1. Lack of insurance coverage 2. Non-compliance with study treatment 3. Disease relapse prior to ASCT. Five patients did not have any grade 3 or 4 adverse events and 1 had disease-related Grade 4 hypercalcemia and Grade 2 AKI at the time of stem cell mobilization. No patients had significant treatment related adverse effects. All 6 patients who completed the protocol achieved the target collection of 5*10^6 CD34 cells/kg. Four patients achieved 6*10^6 CD34 cells/kg or more and the remaining 2 patients achieved 5.52 and 5.92 *10^6 CD34 cells/kg respectively. Among the 6 patients, 2 patients received salvage plerixafor. The median time to achieve WBC >1000/ul, ANC >500/ul and platelets>20k was 11.5, 11, 13.5 daysTable 1AgeInd. RegimneDisease statusPPB CD34/ulCD34 collected *10^6 / kgTotal CD34/kg collectedEngraftment (Days to)Adverse effects from desipramineD1D2D3D4D2D3D4ANC >0.5Platelets> 20kG1,G2G3,G4162 Free λVRDVGPRN45.866.07.017.011213nonenone250 Free λVRDVGPRN88.0143.512.2212.221212nonenone358 IgAVCDVGPRN38.067.731.64.222.756.971317nonenone470 IgAκVRDVGPRY2.4040.216.64.311.615.921214nonenone556 IgGκVCDVGPRY8.7011.937.119.41.334.571.617.511112nonenone670 IgGλVD RDRelapseN76.297.15.545.541120AKIhypercalcemiaP-Plerixafor; V-Velcade; R-Lenalidomide; D-Dexamethasone; C-CyclophosphamideConclusionsOverall G-CSF + Desipramine combination appears to be safe, well tolerated and shows signs of efficacy. G-CSF and desipramine was successful in 4/6 (66%) and all achieved the stem cell collection in 2 days or less. Desipramine, GCSF and Plerixafor was successful in all (6/6) patients to achieve a target of 5*10^6 CD34 cells/kg. The mean number of CD34 cells collected in the desipramine+ G-CSF mobilisers was 7.24*10^6 CD34 cells/kg which, based on historical data, is higher than what would be expected with G-CSF alone even though 3/4 of these patients had lenalidomide as induction therapy. Based on these results, a phase II clinical study evaluating the efficacy of G-CSF with desipramine with or without salvage plerixafor in multiple myeloma and lymphoma will be initiated. DisclosuresBarta:Seattle Genetics: Research Funding.

Cost and Efficacy of Upfront Plerixafor Versus a “Just-in-Time” (JIT) Approach in Hematopoietic Progenitor Cell (HPC) Mobilization

HPC mobilization with plerixafor (Plex) plus G-CSF (G+P) results in superior CD34+ cell yield, when compared to mobilization with G-CSF alone in patients with myeloma and lymphoid malignancies. However, Plex-based approaches are associated with high mobilization costs. To circumvent higher costs, several institutions use a so-called JIT approach, where Plex is only administered to patients likely to fail mobilization with G-CSF alone. Whether such a JIT-Plex approach is cost effective has not been confirmed to date. We present here, a single institution comparative analysis of 137 patients with myeloma and lymphoma who underwent mobilization with 2 different approaches of Plex utilization. Between Jan 2010-Oct 2012 (n=77) patients received mobilization G-CSF (10 μg/kg) for 5 days and Plex (0.24 mg/kg) on the evening of day four, 11 hours before apheresis the following day (G+P). To reduce mobilization costs between Nov 2012-Jun 2014 (n=60) patients were mobilized with JIT-Plex where Plex was only administered to patients likely to fail mobilization with G-CSF alone (i.e. patients with a day 4 peripheral blood (PB) CD34+ count of <10/μL, or those with day 1 yield of < 1.0 X 106 cells/kg or day 1+2 yield of <1.5 X 106 cells/kg ABW. Mobilization failure was defined as inability to collect at least 2 X 106 /kg CD 34+ cells. Patients in G+P had a higher mean peak PB CD34+ cell count (77 vs. 33.1 cells/μL, p<0.001) and a higher mean CD34+ cell yield on day 1 of collection (4.4 X 106 vs. 2.4 X 106 cells/kg ABW, p=0.0005). The mean total CD34+ cell collection was also higher in G+P (6.64 X 106 vs. 4.81 X 106 cells/kg ABW, p=0.0068). In the JIT-Plex group 41% (n=24) completed adequate HPC collection without Plex. Mobilization failure was noted in 5 patients in the G+P group (3 were salvaged with bone marrow harvest) and 2 patients in the JIT-Plex group. Two patients in either group did not proceed to AHCT as a result of mobilization failure. The mean Plex doses utilized in JIT-Plex was lower (1.3 vs. 2.1, p=0.0002), however 21% (n=16) in the G+P group completed apheresis on day 1 compared to only 6.9% (n=4) in JIT-Plex, p=0.0094. Cost analysis was estimated based on actual sales price (actual wholesale price AWP – (AWP X 0.2)) for mobilization agents and the United states (US) Department of Health and Human Services Centers for Medicaid Services (HHS/CMS) reimbursement rates for procedural costs associated with mobilization, apheresis or cryopreservation. The mean estimated cost was higher in the G+P group ($28,448 vs. $24,852, p=0.0315). Our analyses, for the first time confirms that mobilization with JIT-Plex allows for a safe, adequate and cost efficient strategy for HPC collection.Baseline Patent Characteristics at Time of MobilizationTableMobilization StrategyUpfront Plerixafor + G-CSF (n=77)G-CSF + Just-in-time Plerixafor (n=60)p-valueDiseaseMyelomaLymphoma46 (60%) 31 (40%) 30 (50%) 30 (50%)0.29Mean age, years (range)58 (23-75)57 (22-75)0.45Male gender42 (55%)33 (57%)0.92Race: Caucasian73 (97%)57 (98%)1.0Lines of prior therapy, mean1.51.80.3Prior Radiation13 (18%)12 (21%)0.66Mean KPS (range)80 (70-100)80 (60-100)0.75HCT-CI Score (mean)220.36Abbreviations: G-CSF-granulocyte-colony stimulating factor (filgrastim); KPS-Karnofsky performance status; HCT-CI- hematopoietic cell transplantation-specific comorbidity index DisclosuresNo relevant conflicts of interest to declare.

Safety and efficacy of upfront plerixafor + G-CSF versus placebo + G-CSF for mobilization of CD34(+) hematopoietic progenitor cells in patients ≥60 and

The efficacy and safety of plerixafor + G-CSF in enhancing hematopoietic stem cell mobilization and collection has been demonstrated in two phase III studies involving patients with NHL or MM. In these pivotal studies, plerixafor + G-CSF significantly increased the proportion of patients achieving target stem cell yields, compared to placebo + G-CSF. In this analysis, we compare the efficacy and safety of plerixafor + G-CSF versus placebo + G-CSF in patients enrolled in the two phase III studies, stratified by age: ≥60 years of age and <60 years of age. The proportion of older patients who achieved target stem cell yields was significantly higher in the plerixafor group than in placebo group (NHL: 50.9 vs. 25.4%, P < 0.001; MM: 69.6 vs. 23.7%, P < 0.001). In this older cohort, the median times to neutrophil and to platelet engraftment following autologous stem cell transplant were comparable between the plerixafor and placebo groups. Similar efficacy findings were observed in the younger age group. The most common adverse events (all grades) reported among older patients in the plerixafor group included diarrhea (41.3%), nausea (38.9%), fatigue (30.2%), and injection-site reaction (29.4%). The frequency of adverse events was similar between the older and the younger age groups. Taken together, our subanalysis demonstrate that plerixafor + G-CSF can be safely and effectively used in adult patients of all ages, including those ≥60 years, to support optimal stem cell mobilization for autologous stem cell transplantation.

Cost Analysis of Using Plerixafor Plus G-CSF Versus Cyclophosphamide Plus G-CSF for Autologous Stem Cell Mobilization in Multiple Myeloma Patients Treated At Memorial Sloan-Kettering Cancer Center (MSKCC),

Abstract 4059 Background:The combination of cyclophosphamide plus G-CSF has been the standard approach for autologous stem cell mobilization in Multiple Myeloma (MM) patients treated at MSKCC for many years. However with the recent FDA approval of plerixafor and its proven efficacy for stem cell collection in patients who had failed collection with cyclophosphamide and G-CSF, the use of plerixafor as first line agent has been advocated for patients with MM. Although proof of improved efficacy of such an approach over G-CSF/cyclophosphamide mobilization remains paramount, comparison of cost analysis between the 2 approaches is also an important parameter that needs to be considered before endorsing plerixafor as first line mobilization agent. Study Design and Method:We performed a retrospective analysis of all MM patients treated between 11/2008 and 3/2011 who received either cyclophosphamide plus G-CSF or plerixafor plus G-CSF as first line mobilization regimen. During this period of time, the target number of stem cell collection was 10 × 106stem cells/kg and patients collecting less than 4 × 106 stem cells/kg were considered mobilization failures and had a second attempt at stem cell mobilization using an alternative approach. Some patients received plerixafor as salvage regimen after failing cyclophosphamide mobilization, while others were re-challenged with a second cycle of plerixafor with cyclophosphamide and G-CSF after failing first line upfront plerixafor mobilization. Mobilization costs accounted for both groups included the costs associated with upfront mobilization, the second line mobilization in patients failing a first mobilization, as well as complications directly related to the mobilization procedures and consist of the following: Costs of drugs cyclophosphamide 3000 mg/m2, plerixafor 0.24 mg/kg, G-CSF 10 mcg/kg per dose administered prior and during pheresis sessions; hospitalization for cyclophosphamide administration; pheresis sessions; laboratory tests on pheresis days; and re-hospitalization occurring within 15 days of either mobilization approaches and considered directly related to the mobilization procedure. All costs were calculated using the institution’s ratio of cost to charges, and were normalized and adjusted based on institutional charges for 2010. Results:Ninety-eight patients received cyclophosphamide and G-CSF while thirty-five patients received plerixafor as first line mobilization regimens. Eleven (11%) patients were readmitted due to cyclophosphamide complications, with an average hospital stay of 6.9 days, while none in the plerixafor arm was hospitalized. Twenty-one (21%) of the cyclophosphamide group failed mobilization and received plerixafor as salvage regimen of which 3 (3.1%) failed again and are considered ultimate failures. Two (6%) patients failed upfront mobilization with plerixafor and failed salvage mobilization and are considered ultimate failures (6%). The average number of pheresis sessions performed was 3.4 and 2.2 in the cyclophosphamide and plerixafor upfront groups respectively. In total the average cost per patient who received cyclophosphamide was 1.6 times greater than that of the patients who received plerixafor upfront. Conclusion:This cost analysis indicates that the use of plerixafor upfront for stem cell mobilization may be more cost effective than the current widely used approach employing cyclophosphamide. The cost difference between the two approaches could be attributed to several factors: Cyclophosphamide mobilization requires an initial inpatient hospitalization in our institution and often results in re-admissions due to expected toxicity; additionally, the rate of failures, and therefore need for an additional salvage mobilization appears to be much higher with cyclophosphamide; upfront plerixafor was associated with fewer pheresis sessions, and reduced G-CSF use. As many institutions administer cyclophosphamide mobilization on an outpatient basis, it is important to note that the cost benefit of plerixafor upfront remains even if the hospitalization cost of cyclophosphamide mobilization is removed; the cost ratio of cyclophosphamide becomes 1.3 times that of plerixafor. Overall, this single institution study provides, in the context of current clinical practices at MSKCC, the rational for adopting the use of plerixafor as upfront mobilization agent in MM patients. Disclosures:No relevant conflicts of interest to declare.