Plerixafor Group Research Articles

Mobilization strategies with and without plerixafor for autologous stem cell transplant in patients with multiple myeloma.

Autologous stem cell transplantation is a standard treatment strategy for patients with multiple myeloma that requires effective mobilization and apheresis of peripheral blood progenitor cells; however, in the current era of novel myeloma induction therapies, the optimal mobilization regimen to enhance stem cell yield while limiting toxicity and resource utilization remains unknown. In this multicenter retrospective study, we assessed apheresis and transplant outcomes in myeloma patients mobilized with granulocyte colony stimulating factor (G-CSF) alone (n = 62), G-CSF with chemotherapy (n = 43), or G-CSF with the CXCR4 antagonist plerixafor (n = 417). Compared to patients treated with G-CSF alone, the plerixafor group required significantly fewer median apheresis sessions (1 vs 2, p = 0.0023) with higher CD34+ stem cell yield (9.9 vs 5.8 × 106 cells/kg, p < 0.001) and had significantly faster engraftment of neutrophils (HR 1.54, 95% CI 1.17-2.03) and platelets (HR 2.24, 95% CI 1.69-2.96) after transplant. Additionally, the plerixafor group showed a significantly better toxicity profile and lower adverse event rate than patients treated with G-CSF alone (p = 0.0028) or chemomobilization (p < 0.0001), with a trend toward reduced survival in chemomobilization patients. Taken together, these data support the routine use of plerixafor-based mobilization to increase apheresis efficiency and reduce toxicity in myeloma patients undergoing transplant.

On-demand plerixafor added to high-dose cyclophosphamide and pegylated recombinant human granulocyte colony-stimulating factor in the mobilization of patients with multiple myeloma: a treatment with high effectiveness, convenient, and affordable cost.

The combination of high-dose cyclophosphamide (HD-Cy) (3g/m2) plus granulocyte colony-stimulating factor (G-CSF) and on-demand plerixafor (PXF) has been considered an effective mobilization regimen of patients with multiple myeloma(MM). However, the daily multi-injection regimen of G-CSF poses challenges. This study delves into the efficiency and cost implications of a novel approach, using HD-Cy alongside pegylated G-CSF (PEG G-CSF) and on-demand PXF. Unlike G-CSF, which necessitates daily injections, the half-life of PEG G-CSF extended allows for a single injection. A retrospective analysis was conducted on 350 MM patients, which were categorized based on their mobilization regimens: Cy+PEG G-CSF+/-PXF (n=66), Cy+PEG G-CSF (n=91), Cy+ G-CSF (n=169), and G-CSF+PXF (n=24). Mobilization with Cy+PEG G-CSF+/-PXF(8.79)yielded a notably higher median CD34+ cell count compared to the other regimens: Cy+PEG G-CSF(4.96), Cy+G-CSF (4.65), and G-CSF+PXF (2.99) (P<0.001). The percentage of patients who achieved >6×106/kg CD34+ cells was significantly higher in the Cy+PEG G-CSF+/-PXF group (77.3%) than in the other mobilization regimens: Cy+PEG G-CSF (41.8%), Cy+ G-CSF (37.3%), and G-CSF+PXF (8.3%) (P<0.001). From a cost perspective, the Cy+PEG G-CSF+/-PXF approach was more economical than the G-CSF+PXF strategy but was marginally costlier than the other two methods. A multivariate assessment highlighted that the combination of Cy+PEG G-CSF with on-demand PXF had a superior potential to achieve the desired harvest (6×106/kg) compared to the Cy+PEG G-CSF protocol without PXF. The incremental cost-effectiveness ratio for each 1% increase in the probability of achieving a successful optimal harvest was $ 97.02 per patient. The incidence of neutropenic fever was 3.0% in the Cy+PEG G-CSF+/-PXF group. The combination of on-demand PXF with HD-Cy and PEG G-CSF offers a cost-effective approach with a high mobilization success rate, manageable side effects, and the convenience of fewer injections. It stands as a promising mobilization strategy for MM patients.

On-Demand Plerixafor Added to High-Dose Cyclophosphamide and Pegylated Recombinant Human Granulocyte Colony-Stimulating Factorin the Mobilization of Patients with Multiple Myeloma: High Effectiveness and Affordable Cost

Background Autologous stem cell transplantation(ASCT) still represents an integral part of treatment for patients with eligible newly diagnosed multiple myeloma. It is important to collect enough stem cells for two transplants in the first mobilization.The combination of high-dose cyclophosphamide(Cy) (3g/m 2) plus granulocyte colony-stimulating factor(G-CSF)and on-demand plerixafor has been considered the effective method as mobilization regimen, but G-CSF requires daily, multi-injection administration. Here, we performed a real-world analysis to evaluate the efficacy and cost of high-dose Cy combination pegylated recombinant human granulocyte colony-stimulating factor（PEG-rhG-CSF）and on-demand plerixafor for the first time, allowing for a single injection given the long half-life and slow elimination of PEG-rhG-CSF. Methods We retrospectively compared 343 patients whith MM mobilized between August 2008 and December 2022 using the following mobilization strategies: Cy+PEG-rhG-CSF+/-plerixafor(n=61), Cy+PEG-rhG-CSF(n=89),Cy+ G-CSF( n=169), G-CSF+plerixafor(n=24). Then the stem cell mobilization and collection results of the four groups were compared. Results Mobilization with Cy+PEG-rhG-CSF+/-plerixafor resulted in a significantly higher total CD34+ cells ( ×10 6/kg )collected( 8.81) compared to patients mobilized with other mobilization regimens：Cy+PEG-rhG-CSF(5.47；p＜0.001),Cy+ G-CSF(4.65; p＜0.001), G-CSF+plerixafor( 2.99; p＜0.001). Day1+Day 2 CD34+ cells ( ×10 6/kg ) collected were higher in Cy+PEG-rhG-CSF+/-plerixafor group too (Cy+PEG-rhG-CSF+/-plerixafor, 7.87 vs. Cy+PEG-rhG-CSF, 4.96 vs. Cy+ G-CSF,3.92 vs. G-CSF+plerixafor, 2.43) (p＜0.001).The percentage of patients who achieved＞6×10 6/kg CD34+ cells were significantly higher in Cy+PEG-rhG-CSF+/-plerixafor group group (77.0%) than other mobilization regimens：Cy+PEG-rhG-CSF (42.7% ；p＜0.001),Cy+ G-CSF( 37.3% ;p＜0.001）, G-CSF+plerixafor( 8 % ;p＜0.001). Apheresis sessions were fewer in Cy+PEG-rhG-CSF+/-plerixafor group ( Cy+PEG-rhG-CSF+/-plerixafor, 2 vs. Cy+PEG-rhG-CSF,3 vs. Cy+ G-CSF ,3 vs. G-CSF+plerixafor,4)(p＜0.001). Patients proceeded to ASCT with a mean of 2.94 CD34+cell (×10 6/kg ) infused for PEG-rhG-CSF+/-plerixafor , 2.94 infused for Cy+PEG-rhG-CSF, 2.61infused for G-CSF+plerixafor, 3.17 infused for Cy+ G-CSF (p=0.057) . The median time to neutrophil and platelet engraftment not different in the four groups. The total cost of mobilization and apheresis using Cy+PEG-rhG-CSF+/-plerixafor was significant lower ($5670.64) compared to G-CSF+plerixafor group($11098.61), and significant higher than Cy+PEG-rhG-CSF group ($3842.23)and Cy+ G-CSF group($3727.82)（p＜0.001）. Multivariate analysis showed that patients who received Cy+PEG-rhG-CSF +/-plerixafor treatment had significantly higher likelihoods of successfully achieving the optimal harvest (6×10 6/kg) in respect to Cy+PEG-rhG-CSF group mobilized without any plerixafor. The incremental cost-effectiveness ratio, for each 1% increase in probability of achieving a successful optimal harvest, was $62.57 per patient. The incidence of neutropenic fever not different in the Cy+PEG-rhG-CSF+/-plerixafor group(4%), Cy+PEG-rhG-CSF group (10%) and Cy+ G-CSF group(18%)(p=0.051). There was no patients suffered with neutropenic fever in G-CSF+plerixafor group. Conclusion Given higher rates of successful mobilization, affordable cost and toxicity, on-demand plerixafor added to high-dose Cy and PEG-rhG-CSF may be preferable in the mobilization of patients with multiple myeloma.

Comparison of different plerixafor-based strategies for adequate hematopoietic stem cell collection in poor mobilizers

Objectives: The main objective of the present study was to evaluate whether the use of plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) or subsequent use of isolated G-CSF and then plerixafor following disease-specific chemotherapy, and whether it would allow for adequate peripheral stem cell collection in patients. Methods: The retrospective study evaluated 54 patients with previous mobilization failure who were administered plerixafor in 2 centers. In patients without any side effects, CD 34+ cell counts, the percentage of patients who were found eligible for autologous transplantation, the engraftment kinetics of the patients who underwent transplantation, and their overall survival results were compared between the two groups where G-CSF was used with plerixafor, or where plerixafor was used after isolated G-CSF following chemotherapy. Results: The median age of the patients was 49 years (range: 17-70), and 64.8% (n = 35) were males. It was identified that 31 (57.4%) patients underwent mobilization treatment with isolated G-CSF and plerixafor, and 23 (42.6%) patients underwent mobilization treatment with chemotherapy plus G-CSF and plerixafor. In all patients, mean hemoglobin level (11.3 ± 1.5 g/dL vs. 9.3 ± 1.3 g/dL; p &amp;lt; 0.001) and median platelet level (129.2 ×103/µL vs. 58.4 ×103/µL) were found to be higher, while febrile neutropenia rate (3.3% vs. 60.9%), the percentage of replacement patients (6.7% vs. 65.2%), and median days of G-CSF (6 vs. 9) were found to be lower on the day of plerixafor administration in the isolated G-CSF and plerixafor group compared to the chemotherapy and G-CSF and plerixafor group. Conclusions: In conclusion, our study demonstrated that administration of plerixafor is generally safe and well-tolerated. Regardless of the underlying disease, it offers an effective alternative for patients with previous failed mobilization attempts using conventional regimens, and allows stem cell collection with fewer apheresis sessions.

Poor Mobilizers in Lymphoma but Not Myeloma Patients Had Significantly Poorer Progression-Free Survival after Autologous Stem Cell Transplantation: Results of a Large Retrospective, Single-Center Observational Study.

In our single-center study, 357 myeloma and lymphoma patients between 2009 and 2019 were mobilized with granulocyte colony-stimulating factor (G-CSF 7.5 µg/kg bid for four days) plus a fixed dose of 24 mg Plerixafor when indicated (Plerixafor Group, n = 187) or G-CSF alone (G-CSF Group, n = 170). The target CD34 cell yields were ≥2.0 × 106 CD34+ cells/kg in lymphoma and ≥4.0 × 106 CD34+ cells/kg in myeloma patients to enable putative second transplants in the latter. There were no significant differences in engraftment kinetics or transfusion requirements between the Plerixafor Group and the control group in the myeloma cohort, with lymphoma patients not requiring Plerixafor showing significantly faster neutrophil recovery, a trend to faster platelet recovery, and a significantly lower need for platelet transfusions, probably due to the significantly lower number of CD34-positive cells re-transfused. While in myeloma patients the outcome (overall survival, progression-free survival) following autologous stem cell transplantation (ASCT) was similar between the Plerixafor Group and the control group, hard to mobilize lymphoma patients had significantly poorer progression-free survival (47% vs. 74% at 36 months after ASCT, p = 0.003) with a trend also to poorer overall survival (71% vs. 84%). In conclusion, while there seem to be no differences in stemness capacity and long-term engraftment efficiency between the Plerixafor and the G-CSF Group in lymphoma as well as myeloma patients, poor mobilizing lymphoma patients per se constitute a high-risk population with a poorer outcome after ASCT. Whether disease characteristics and/or a more intense or stem cell-toxic pre-mobilization chemo-/radiotherapy burden in this cohort are responsible for this observation remains to be shown in future studies.

P-800 Plerixafor for endogenous mobilisation of mesenchymal stem cells to induce endometrial regeneration

Abstract Study question Will the treatment with plerixafor alone or associated with β3 agonist cause endometrial regeneration and consequently improve the reproductive outcome of mice with thin endometrium? Summary answer The combined treatment with plerixafor and β3 agonist improved the reproductive outcomes, indicating a potential therapeutic option for infertility related to thin endometrium. What is known already Thin endometrium represents a huge challenge in assisted reproduction, since it is related to decreased endometrial receptivity and consequent implantation failure. The treatments with mesenchymal stem cells (MSC) have regenerative properties that improve endometrial thickness and expression of receptivity biomarkers. Plerixafor is a CXCR4 antagonist receptor that disrupts the CXCL12-CXCR4 axis, which is directly related to stem cell migration, and has been used in tissue regeneration studies to increase the influx of stem cells to the site of injury. In addition, its combined use with β3 adrenergic agonist receptors leads to selective recruitment of MSC with better regenerative results. Study design, size, duration Experiments were carried out on female C57Bl/6 mice (age 9 weeks; 20g). Forty-eight individuals were assigned for either thin endometrium induction or sham procedure; then, mice in each group were randomly divided into three treatment subgroups (n = 8): (1) Placebo - phosphate-buffered saline, (2) plerixafor, (3) plerixafor and BRL37344 (rodent-selective β3 adrenergic receptor agonist). Two estrous cycles after modelling and treatment, all groups were mated with proven C57Bl/6 male mice for four weeks. Participants/materials, setting, methods Thin endometrium was induced by direct injection (50 μl) of 95% ethanol in the surgically exposed uterus, while Phosphate-buffered saline (PBS) was used in the sham procedure. Regarding the treatments, the groups received: (1) PBS (5 mg/kg sc) single-dose after surgery, (2) plerixafor (5 mg/kg sc) single-dose after surgery, (3) BRL37344 (rodent-selective β3 adrenergic receptor agonist) (10 mg/kg sc) for four consecutive days previous to surgery plus plerixafor (5 mg/kg sc) single-dose. Main results and the role of chance The pregnancy rate and litter size were analysed in order to establish the impact on the reproductive outcomes. In addition, a macroscopic anatomic analysis was performed on the offspring to evaluate possible teratogenic effects. Concerning pregnancy rates, 23 out of 24 sham mice got pregnant (despite the treatment group). The thin endometrium model reproduced the literature results, with under 30% of failure in inducing endometrial damage, represented by a pregnancy rate of 25% (2/8) in the PBS group in comparison to all sham groups (p &amp;lt; 0,05). The plerixafor plus β3 agonist treatment completely restored the endometrial function, promoting pregnancy rates similar to all sham groups (p &amp;gt; 0,05). There was no difference between the plerixafor alone group and all the other groups (p &amp;gt; 0.05) in terms of pregnancy, although a clinically relevant difference between placebo and plerixafor alone group was found (25% versus 62,5%, respectively). The litter size was similar between the treatment groups, except for the plerixafor group with a smaller number of newborns. Regarding the teratogenic potential of the tested drugs (plerixafor and β3 agonist), we did not observe any relevant macroscopic malformations (internal and external) in the treated groups. Limitations, reasons for caution There is a need to establish the biological mechanisms responsible for endometrial recovery. Moreover, this study provided treatment for an acute injury; therefore, future work should evaluate the application on long term endometrial damage. The long term effect of the single-dose treatment should also be assessed. Wider implications of the findings Our findings indicate a potential therapy for thin endometrium. Plerixafor and β3 agonist treatment resulted in an expressive improvement in reproductive outcomes, without a detrimental impact on offspring. Moreover, this treatment utilises two clinical approved classes of drugs, which could reduce the timeline and cost of translational applications in future. Trial registration number not applicable

The Effect of Daratumumab, Lenalidomide, Dexamethasone (DRd) on Peripheral Blood Stem Cell Mobilisation (PBSC)

The Effect of Daratumumab, Lenalidomide, Dexamethasone (DRd) on Peripheral Blood Stem Cell Mobilisation (PBSC)

Second Autologous Stem Cell Transplantation in Poor Stem Cell Mobilizers Multiple Myeloma Patients

Second Autologous Stem Cell Transplantation in Poor Stem Cell Mobilizers Multiple Myeloma Patients

Stem Cell Mobilization in Multiple Myeloma: Comparing Safety and Efficacy of Cyclophosphamide +/- Plerixafor versus Granulocyte Colony-Stimulating Factor +/- Plerixafor in the Lenalidomide Era

Growth factor and chemotherapy-based stem cell mobilization strategies are commonly used to treat patients with multiple myeloma. We retrospectively compared 398 patients mobilized between 2017 and 2020 using either cyclophosphamide (4 g/m2) plus granulocyte colony-stimulating factor (G-CSF) or G-CSF alone, with on demand plerixafor (PXF) in both groups. Although total CD34+yield was higher after chemomobilization compared with G-CSF +/- PXF (median, 13.6×106/kg versus 4.4×106/kg; P < .01), achievement of≥2×106CD34+ cells (95% versus 93.7%; P=.61) and rates of mobilization failure (5% versus 6.3%; P=.61) were similar. Fewer patients required PXF with chemomobilization (12.3% versus 49.5%;P < .01), and apheresis sessions were fewer (median, 1 [range, 1 to 4] versus 2 [range, 1 to 5]). The rate of complications, including neutropenic fever, emergency department visits, and hospitalizations, was higher after chemomobilization (30% versus 7.4%;P < .01). Previous use of ≤6 cycles of lenalidomide did not impair cell yield in either group.The median cost of mobilization was 17.4% lower in the G-CSF +/- PXF group (P=.01).Between group differences in time to engraftment were not clinically significant. Given similar rates of successful mobilization, similar engraftment time, and less toxicity and lower costs compared with chemomobilization, G-CSF with on-demand PXF may be preferable in myeloma patients with adequate disease control and limited lenalidomide exposure.

Optimization of Plerixafor Utilization Based on Peripheral Blood CD34+ Count for Autologous Peripheral Blood Stem-Cell Collection

Introduction: Peripheral CD34+ cells may be mobilized using filgrastim (G-CSF) alone or in combination with chemotherapy. However, some patients also require plerixafor, an inhibitor of C-X-C chemokine receptor type-4, for adequate mobilization. Given its cost, judicious utilization of plerixafor is warranted. Material and Methods: A retrospective analysis of autologous stem-cell mobilization was performed at a tertiary-care medical center in adult patients with multiple myeloma and lymphoma; here we will focus on the utility of repeat plerixafor dosing. Patients were mobilized at the treating physician's discretion with filgrastim plus plerixafor or chemotherapy plus filgrastim plus plerixafor. Collections were initiated once peripheral CD34+ counts reached 20/µL (or 10/µL if chemotherapy mobilized); plerixafor was administered if these counts were not reached after 4 or 8 days, respectively, of filgrastim treatment. Results: Patients with multiple myeloma (86) or lymphoma (30) were evaluated. One hundred five were mobilized by filgrastim plus plerixafor and 11 by chemotherapy plus filgrastim plus plerixafor. No patient that received plerixafor with a CD34+ count &amp;lt;5/µL after chemotherapy mobilized the next day. The end collection goal was achieved in 86 (81.9%) of the filgrastim plus plerixafor group and 7 (63.6%) of the chemotherapy plus filgrastim plus plerixafor group. Patients given at least one dose of plerixafor were divided into groups based on collection goal, peripheral blood CD34+ cell count after 1 dose and the first day collection yield: Group 1) Goal of 3x10^6/kg and CD34+ count ≥ 30 cell/µL vs &amp;lt; 30 cell/µL; Group 2) Goal of 6x10^6/kg and ≥ 50% of collection goal after 1 day of collection vs CD34+ count &amp;lt; 50 cell/µL or &amp;lt; 50% of collection goal. Forty of 42 (95%) patients in Group 1 with a CD34+ count ≥ 30 cell/µL achieved their end collection goal after one plerixafor dose. Eighteen of 19 (95%) patients in Group 1 with a CD34+ count &amp;lt;30 cell/µL received a second dose of plerixafor and 8 (44.4%) achieved their end collection goal. Twenty-eight of 32 (87.5%) patients in Group 2 with ≥ 50% of collection goal achieved on the first day of collection reached their end collection goal after one plerixafor dose. Nine of 12 (75%) patients in Group 2 with a CD34+ count of &amp;lt; 50 cells/µL or &amp;lt;50% collection goal received an additional dose of plerixafor and 6 (66.7%) achieved their end collection goal. Conclusion: Based on these data, we have developed the following repeat plerixafor dosing algorithm: 1) for a collection goal is 3x10^6/kg, administer a second dose of plerixafor if the CD34+ count on the first day of collection is &amp;lt; 30 cell/µL, and 2) for a collection goal of 6x10^6/kg, administer a second dose of plerixafor if the CD34+ count on the first day of collection is &amp;lt; 50 cell/µL or if the first day of collection yields &amp;lt;50% of the end goal. This algorithm optimizes pharmacy, apheresis and stem cell processing resources. Disclosures No relevant conflicts of interest to declare.

Plerixafor-based mobilization in pediatric healthy donors with unfavorable donor/recipient body weight ratio resulted in a better CD34+ collection yield: A retrospective analysis.

In order to propose risk-adapted mobilization algorithms, several authors have tried to look for predictive factors of the CD34+ yield in healthy pediatric donors. Donor recipient body weight ratio (D/R ratio) was identified as one of the main variables related with the success to achieve the target cell dose for transplantation. According to this variable we modified the mobilization schedule. We report the results of 46 mobilizations and apheresis procedures performed in our center with unfavorable D/R ratio. Mobilization was attempted by the standard regime of G-CSF (10 mcg/kg/24 hours) in 28 cases (60.9%), with high dose G-CSF (10 mcg/kg/12 hours) in 9 cases (19.6%), and with plerixafor and G-CSF single dose regime in 9 cases (19.6%). CD34+ cell quantification before apheresis is closely related to CD34+ yield, being the only factor related to collected CD34+ cells (beta .71; P < .0001). The mobilization efficiency was higher in plerixafor group compared to the other two schedules (P < .0001). By using plerixafor for mobilization, we achieved the target CD34+ cell dose of ≥2 × 106 /kg per recipient body weight in all cases with unfavorable D/R ratio. It was observed that 17.4% of cases that not reached the established target cell dose were located in the standard or high-dose mobilization regimes. This difference is even greater for optimal collections (≥5 × 106 /kg), since of the 54.3% cases that did not reach this goal none was mobilized by plerixafor. Tailoring the mobilization regime we can reach the target cell dose, even in those cases with the worst D/R ratio.

Cost and efficacy of peripheral stem cell mobilization strategies in multiple myeloma.

Mobilization of peripheral blood stem cells (PBSC) can be performed using plerixafor, which is expensive, or high-dose cyclophosphamide (HDCy). We hypothesized that the overall cost of mobilization with plerixafor might not be greater if the cost of complication management was considered. We performed a cost analysis of these two strategies. This multicentric observational study recruited patients with myeloma who underwent a first PBSC mobilization. We considered direct medical costs, including hospitalization, mobilization agents, apheresis, and supportive treatments. We included 111 patients, 54 and 57 in the HDCy and plerixafor groups, respectively. Cost of mobilization with HDCy was 5097 ± 2982€ vs. 10958 ± 1789€ for plerixafor (p < 0.0001). Cost of agents used was 1287 ± 779€ vs. 6552 ± 509€, respectively (p = 0.0009). The mean number of days of hospitalization was 2 and 2.1 days, respectively (p = 0.035). All patients achieved the minimum PBSC collection target (p = 1.0); however, ASCT was performed with HDCy in 67% patients and with plerixafor in 86% (p = 0.02). Plerixafor mobilization incurred a greater cost, mostly due to the greater cost of the drug. Hospitalization length in the two groups was similar in our series. Interestingly, plerixafor appeared to be a very effective and safe mobilizing approach translating into a greater ASCT success.

Mobilization regimen, including Plerixafor, does not impact CD34 recovery after automated post-thaw processing

Background & Aim Autologous Hematopoietic stem cell (HSC) transplantation is still widely used to overcome hematologic toxicity after high dose chemotherapy for patients with hematological malignancies such as multiple myeloma or lymphoma among others. In most cases, HSC are collected by apheresis after an appropriate mobilization regimen. At our institution, cryopreserved autologous grafts are thawed and washed before infusion. All these processing steps can be performed manually or via automated processes or devices. We aimed to evaluate the impact of mobilization regimen on rh-G-CSF or Plerixafor graft quality when using standardized, automated processes. Methods, Results & Conclusion Methods Between 2016 and 2019, 535 patients received an autologous transplant at our institution. From this cohort, we extracted 260 patients (n=170 myeloma and n=90 myeloma) for whom processing of the apheresis product was comparable, i.e. cryopreservation the same day of the HSC procurement in 2 bags, standardized thawing using Smartmax followed by automated washing using the Sepax-2. Among this cohort, 90 patients (n=75 myeloma and n=15 lymphoma) received Plerixafor + rh-G-CSF as a mobilization regimen, and 170 patients (n=95 myeloma and n=75 lymphoma) received a standard regimen (either rh-G-CSF alone or rh-G-CSF in addition to chemotherapy for lymphoma). Measurable outputs were CD34+ cells/ kg before and after thawing, CD34+ cells recovery and viability, CD45+ cells/kg, neutrophils and myelemia before cryopreservation and CD45+ cells viability after thawing. Results Apheresis products collected from patients mobilized with Plerixafor versus rh-GCSF showed lower HSC content (3,2 × 106/kg versus 5 × 106/kg respectively) and lower myelemia (7 × 106/kg versus 12,9 × 106/kg respectively, p=0.005). Total CD45+ and neutrophils contents were similar (median 50 × 109 and 3 × 109 respectively, p = NS). CD45+ and CD34+ viabilities were comparable between the two regimen (around 83% and 85% respectively p = NS). For both groups, viable CD34+ cells recovery was similar (median 79% for the plerixafor group versus 76% for the rh-G-CSG group p = NS). Conclusions Our data show that CD34+ cells recovery is not affected by the nature of mobilization agents when using standardized automated processing post-cryopreservation.

A Comparison of the Effect of Granulocyte-Colony Stimulating Factor (G-CSF) in Chemotherapy Versus Plerixafor for Hematopoietic Stem Sell Transplantation (HSCT) and Mobilization

INTRODUCTION: Peripheral Hematopoietic Stem Cells have been widely used as a source for Autologous Hematopoietic Stem Cell Transplantation (HSCT). The use of G-CSF associated with chemotherapy increases the number of circulating Hematopoietic Progenitor Cells; however, there is no harmony about the best medical strategy for the use of G-CSF associated with the mobilization conduct. The use of plerixafor for poorly mobilized patients has provided a safe and effective option for optimizing apheresis procedures despite the high cost. Thus, the evaluation of efficacy becomes essential for the incorporation of plerixafor into the HSCT routine. OBJECTIVE: To evaluate the mobilization of autologous HSCT in chemotherapy associated with G-CSF and cyclophosphamide (QT) versus plerixafor. METHODS: Retrospective evaluation of 66 patients mobilized for autologous HSCT with G-CSF associated with chemotherapy versus plerixafor (plerixafor was used in the first mobilization), also to evaluate the number of apheresis procedures, CD34-positive cells, cell viability and for the bone marrow engraftment date. Statistical analyses were performed with GraphPad Prism 5.0 (GraphPad Software, Inc., San Diego, CA), using the Mann-Whitney test for nonparametric data (p &lt;0.05). RESULTS: A mobilization protocol was performed in 83 patients (60% male), with a median age of 55 years (17 to 68 years). Multiple myeloma (55.7%), Hodgkin's lymphoma (14.7%), Non-Hodgkin's lymphoma (16.39%), primary amyloidosis (4.9%) were the most common hematologic malignancies. There was no statistical difference between G-CSF and QT group versus plerixafor groups regarding age, sex, type of disease and previous QT. The plerixafor group had better CD34 positive cell counts compared to G-CSF and QT (median 6.2 versus 3.8 x106, p&lt;0.004), shorter sessions of apheresis procedure (median 2 versus 4, p &lt; 0.0002) and a better cell viability rate (98 versus 95%, p &lt;0.0034). The bone marrow engraftment rate was 10 days for plerixafor group versus 15.05 days for G-CSF and QT group, p &lt;0.0055 (Figure 1).CONCLUSION: Our results showed the mobilization group using plerixafor had superior data and statistical significance regarding the number of apheresis procedures, cell viability, number of CD34 positive stem cells and earlier bone marrow engraftment rates when compared to the G-CSF + QT. These findings suggest and encourage the use of plerixafor in the first mobilization, as well as it should be incorporated into the standard routine. In addition, the number of apheresis procedures will be reduced, cell viability and CD34-positive cells rate will be increased. As a result, there will be a better medullary recovery and the reducing of both hospital costs and infectious complication rates. Disclosures No relevant conflicts of interest to declare.

Evaluation of the Role of Plerixafor in Peripheral Blood Progenitor Cell Mobilization and Collection in Autologous Donors with Multiple Myeloma and Non-Hodgkin Lymphoma

Purpose Autologous hematopoietic stem cell transplantation is commonly used as treatment for patients with Multiple Myeloma (MM) or Non-Hodgkin Lymphoma (NHL). The mobilization and collection of peripheral blood progenitor cells (PBPC) to reach the required cell dose for transplantation is problematic for some patients when standard mobilization agents such as G-CSF, alone or combined with chemotherapy, are used. These patients are considered poor mobilizers with &lt; 20 CD34+ cells /μl on the planned day of collection and the optimal strategy to collect a sufficient number of PBPC in poor mobilizers is still not fully known. Plerixafor, a CXCR4 inhibitor, when added to the standard mobilization regimen, has been shown to improve mobilization and increase the probability of collecting a PBPC graft &gt; 2 X106CD34 /kg in standard mobilizers. In our center, Plerixafor became available in October 2012. However, how best to use plerixafor to improve care for poor mobilizers while ensuring the most cost-effective use of health care resources for this patient population remains an important question. To begin answering this question, we evaluated the impact of plerixafor usage in our population of poor mobilizers in our institution using a historical cohort for comparison. Material and method The population of poor mobilizers in the setting of MM or NHL (defined as &lt; 20 CD34 / μl on the planned day of collection) between January 2009 and December 2017 at Hôpital de l'Enfant Jesus (HEJ) du CHU de Québec was retrospectively studied and analyzed. To ensure that all poor mobilizers were included, we screened all flow cytometry CD34+ cell count results &lt; 50 /μl on the planned day of collection and reviewed all the charts of patients with &lt; 20 CD34 / μl regardless of whether they were collected or not. This chart review allowed a comprehensive description of the characteristics of our poor mobilizers, a comparison of the capacity to collect an adequate PBPC with or without plerixafor and to evaluate its impact on different variable with regard to PBPC collection and subsequent engraftment. The data were compiled in an ACCESS database using a retrospective review of digital patient charts. The data was analyzed by the Centre de Recherche du CHU de Quebec (CRCHUQ). Data were stratified by disease type and CD34 level on the planned day of PBPC collection. Results 207 patient charts were reviewed; 70 poor mobilizers with 95 mobilizations attempts, 30 of them using plerixafor, were included. The baseline characteristics of both groups were similar as well as the length of hospitalization for transplant and relapse free survival at one year. The addition of Plerixafor to our management of poor mobilizers did not significantly increase the proportion of patients proceeding to autologous PBPC transplant (80,4 vs 75% p=0,7599). During the mobilization attempts, the maximal CD34 /μl reached was similar in both groups (18,86 vs 15,4 p=0,1541). Plerixafor was associated with a superior collection efficiency (% of CD34 collected) (40,85 vs 60,91% p=0,007), but this can be explained by a greater use of central venous catheters for collection in this group (70 vs 95,1% p = 0,0275). Data stratified by initial diagnosis and CD34 level on the planned day of PBPC collection (&lt;10 c/μl versus [10c/μl - 20c /μl [) showed the same tendency. The collection duration was not significantly reduced in the plerixafor group, but there was a trend for a shorter mean duration of 22 minutes also explained by a greater use of central venous catheters in this group. The preplanned subgroups analyses have shown the same trend when stratified by diagnosis, with a reduction of 53 minutes in the multiple myeloma subgroup with a greater total CFU-GEM / kg per collect (46,35 vs 70,55 p=0,0163). Conclusion The use of plerixafor at HEJ did not improve significantly the proportion of poor mobilizers reaching an adequate PBPC graft and did not improve transplant outcomes compared to a historical control. Better strategies are needed to improve care for true poor mobilizers. The optimal use of plerixafor needs to be further studied. Table. Disclosures Blais-Normandin: Sanofi: Other: unrestricted research grant. Laroche:Sanofi: Other: unrestricted research grant.

A Retrospective Record Review of Mobilization Strategies with and without Plerixafor for Autologous Stem Cell Transplant in Patients with Multiple Myeloma

Background: Autologous hematopoietic stem cell transplantation (ASCT) is the current standard of care in patients with multiple myeloma (MM) to support reconstitution of the bone marrow after myeloablative chemotherapy. Mobilization of blood progenitor cells to the peripheral circulation is stimulated via administration of granulocyte colony-stimulating factor (G-CSF) with or without chemotherapy. The addition of chemotherapy, typically cyclophosphamide, increases the yield of peripheral blood stem cells (also known as CD34+ cells) at the expense of additional toxicity. The unpredictability of harvest yield and the potential need for weekend apheresis sessions complicates mobilization planning when using chemotherapy. Plerixafor, a CXCR4 antagonist, in combination with G-CSF has been shown to be superior to G-CSF alone, leading to higher CD34+ yields in fewer apheresis sessions [Giralt et al, 2014]. However, the advantage of the combination of plerixafor with G-CSF is less well described in the context of new treatment options that can impair stem cell harvest yields when using G-CSF as the sole mobilization agent. Objective: The primary objective of this study was to determine clinical outcomes associated with G-CSF alone vs G-CSF + chemomobilization vs G-CSF + plerixafor from initiation of mobilization until 6 to 12 months after ASCT. Method: This is a retrospective study in patients with MM, carried out at 10 centers in the US. Patients were eligible if ≥ 18 years and undergoing first ASCT (≤ 12 months from initial diagnosis and no disease progression). Eligible patients were identified through a database query of hospital records of oncology patients diagnosed with MM and eligible for ASCT before June 2016. Patients fulfilling inclusion and exclusion criteria were attributed to three treatment arms depending on the mobilization regimen received:Arm 1: G-CSF + plerixaforArm 2: G-CSF + chemomobilizationArm 3: G-CSF Patients will be selected until 170 patients are assigned to each treatment arm or patient records are exhausted. Demographics, induction regimen, mobilization regimens and outcomes, apheresis, transplantation outcomes and survival status were extracted from medical charts and entered in the electronic case report form. Here, we present interim results from data collected at three centers as of June 24, 2019. Results: At the interim analysis cut-off date, 130 patients were included in the database (G-CSF: 52; G-CSF + plerixafor: 78; G-CSF + chemomobilization: 0). Demographic and baseline characteristics were comparable between the two treatment arms. More male patients were included (male: 63%, female: 37%) and the mean age was 58 and 59 years in the G-CSF and G-CSF + plerixafor groups, respectively (Table 1). Disease stage and the proportion of patients with poor-, intermediate- and high-cytogenetic risk status were similar in the two treatment groups. Few patients had a complete response (CR) after chemotherapy, but response rate (CR + partial response) was 91% in both treatment arms. The burden of apheresis in terms of number of sessions and blood volume processed was lower in patients receiving G-CSF + plerixafor compared with patients receiving G-CSF only (Table 2). CD34+ yield was higher in the G-CSF + plerixafor treatment arm, especially after the first apheresis session (Table 2). There was no difference in ASCT outcome between the two treatment groups. All patients had neutrophil engraftment except for one patient in the G-CSF only group, and all patients had platelet engraftment except one patient in each treatment group. There was no significant difference in the proportion of patients experiencing relapse between the two treatment groups at 6 and 12 months of follow-up. Overall, ≥ 90% of patients avoided relapse at 12 months. 96% and 93% of patients were still alive at 12 months in the G-CSF only and G-CSF + plerixafor treatment groups, respectively (Table 3). For the purpose of this study, safety data was not reviewed [Mozobil PI, 2019]. Conclusions: Per interim results, plerixafor reduced the burden of apheresis and increased CD34+ yields. Transplantation outcomes, relapse and overall survival at 6 and 12 months were not significantly different between the two treatment arms. Therefore, plerixafor could increase apheresis efficiency without compromising ASCT success in the context of currently used chemotherapy regimens. Disclosures Mark: Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria. Bubalo:Sanofi: Other: Research and writing support. Barnes:Sanofi: Employment. Drea:Sanofi-Genzyme: Employment. Fausel:Sanofi-Genzyme: Other: Grant to cover costs of data collection.

Analysis of data collected in the European Society for Blood and Marrow Transplantation (EBMT) Registry on a cohort of lymphoma patients receiving plerixafor

Plerixafor + granulocyte-colony stimulating factor (G-CSF) is administered to patients with lymphoma who are poor mobilizers of hematopoietic stem cells (HSCs) in Europe. This international, multicenter, non-interventional registry study (NCT01362972) evaluated long-term follow-up of patients with lymphoma who received plerixafor for HSC mobilization versus other mobilization methods. Propensity score matching was conducted to balance baseline characteristics between comparison groups. The following mobilization regimens were compared: G-CSF + plerixafor (G + P) versus G-CSF alone; G + P versus G-CSF + chemotherapy (G + C); and G-CSF + plerixafor + chemotherapy (G + P + C) versus G + C. The primary outcomes were progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR). Overall, 313/3749 (8.3%) eligible patients were mobilized with plerixafor-containing regimens. After propensity score matching, 70 versus 36 patients were matched in the G + P versus G-CSF alone cohort, 124 versus 124 in the G + P versus G + C cohort, and 130 versus 130 in the G + P + C versus G + C cohort. For both PFS and OS, the upper bound of confidence interval for the hazard ratio was >1.3 for all comparisons, implying that non-inferiority was not demonstrated. No major differences in PFS, OS, and CIR were observed between the plerixafor and comparison groups.

Real-world experience of administering plerixafor (MOZOBIL) for autologous peripheral blood stem cell harvest

Background & Aim From February 2017, the immunostimulant, plerixafor (Mozobil) became covered by insurance in Japan, and in the following month the drug was introduced into treatment for patients with haematological malignancies at Japanese Red Cross Medical Centre. The purpose of this retrospective study was to report experiences with administration of plerixafor for the mobilization and collection of hematopoietic stem cells, treatment outcomes and apheresis efficiency. Methods, Results & Conclusion Hospital records from patients undergoing peripheral blood stem cell harvest for autologous transplantation were reviewed between January 2016 and December 2018. A total of 134 patients (71 male, 63 female), aged from 19 to 69 years (mean age, 55.7 years) were collected. Of these, 89 patients (66.4%) were diagnosed with multiple myeloma, 24 patients (17.9%) with AL amyloidosis, 17 patients (12.7%) with non-Hodgkin's lymphoma, and 4 patients (3.0%) with other diseases. This cohort underwent 174 sessions of apheresis. Seventy-one of all patients (53.0%) were mobilized using plerixafor in combination with granulocyte-colony stimulating factor (G-CSF), while 63 patients (47.0%) were mobilized without plerixafor. Successful treatment outcome was defined as collecting ≥ 2.0 × 106 CD34+ cells per patient's body weight (/kg) following mobilization. In the plerixafor plus G-CSF treatment group, successful collection was observed in 64 of 71 patients (90.1%) and mobilization failure in 7 patients (9.9%). Of these, 55 patients (77.5%) were completed in one apheresis session. In the other group, without plerixafor, successful collection was observed in 50 of 63 patients (79.4%), and mobilization failure in 13 patients (20.6%). Of these, 44 patients (69.8%) were completed in one apheresis session. An increase in median CD34+ cells collected of 3.8 (1.0-11.9) × 106/kg without plerixafor to 5.3 (0.5-16.7) × 106/kg with plerixafor was observed. With the use of plerixafor, mobilization and collection of CD34+ cells was increased and the number of apheresis sessions required per patient showed a tendency to be reduced.

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.

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.