Preemptive Plerixafor Research Articles

Preemptive Approach to Plerixafor Use Is Optimal in Patients With Relapsed/Refractory Germ Cell Tumors Undergoing Peripheral Blood Hematopoietic Stem Cell Collection: Effect on Collection Days, Yields, and Cost.

Evidence describing the use of plerixafor in the off-label population of relapsed/refractory germ cell tumors (GCT) is limited. Weaim to describe the effect of rescue versus preemptive plerixafor use on apheresis collection days, collection yields, and cost. We retrospectively collected data on 77 consecutive patients (at least 15 years of age) with GCT who underwent peripheral blood stem cell (PBSC) collection for autologous stem cell transplant between January 1, 2020 and May 1, 2022. Depending on insurance approval, plerixafor was given either as "rescue" (after a first apheresis collection of < 5 × 106 CD34+ cells/kg) or as "preemptive" on Day 4 of granulocyte-colony stimulating factor (G-CSF) prior to the first apheresis collection, if the Day 4 peripheral blood CD34+ count was < 40 cells/μL. A total of 66% of patients who received preemptive plerixafor completed collection in 1 day, similar to good mobilizers who only needed G-CSF (71%, p = 0.366). In contrast, all poor mobilizers in the rescue group required at least 2 days of collection and had lower CD34+ cell yields than the preemptive group (7.15 vs. 9.81 × 106/kg, p = 0.0055). A cost analysis revealed that preemptive plerixafor may save approximately $7000 per patient compared with a rescue approach. Preemptive plerixafor in GCT patients undergoing PBSC collection allows relatively poor mobilizers to collect in fewer days and with lower overall cost. Fewer apheresis procedures result in less risk to the patient, increased patient satisfaction, and the ability to schedule more patients within the constraints of staffing.

Optimizing autologous stem cell collections for patients with multiple myeloma receiving G-CSF and Plerixafor: A single center project.

Increasing indications for cellular therapy collections have stressed our healthcare system, with autologous collections having a longer than desired wait time until apheresis collection. This quality improvement initiative was undertaken to accommodate more patients within existing resources. Patients with multiple myeloma who underwent autologous peripheral blood stem cell collection from October 2022 to April 2023 were included. Demographic, mobilization, laboratory, and apheresis data were retrospectively collected from the medical record. This cohort included 120 patients (49.2% male), with a median age of 60 years. All received G-CSF and 95% received pre-emptive Plerixafor approximately 18 hours pre-collection. Most (79%) had collection goals of at least 8 × 106/kg CD34 cells, with 63% over 70 years old having this high collection goal (despite 20 years of institutional data showing <1% over 70 years old have a second transplant). With collection efficiencies of 55.9%, 44% of patients achieved their collection goal in a single day apheresis collection. A platelet count <150 × 103/μL on the day of collection was a predictor for poor mobilization; among 27 patients with a low baseline platelet count, 17 did not achieve the collection goal and 2 failed to collect a transplantable dose. With minor collection goal adjustments, 15% of all collection appointments could have been avoided over this 6-month period. Other strategies to accommodate more patients include mobilization modifications (Plerixafor timing or substituting a longer acting drug), utilizing platelet counts to predict mobilization, and modifying apheresis collection volumes or schedule templates.

Comparison of Various Stem Cell Mobilization Regimens for Multiple Myeloma - a 15-Year Retrospective Institutional Analysis from India

Introduction For multiple myeloma (MM), Cyclophosphamide (Cy) based chemo-mobilization offers advantage in term of higher stem cell yield and can overcome adverse impact of prior lenalidomide therapy on stem cell harvest. However, considering need for hospital stay and risk of febrile neutropenia, steady state mobilization with G-CSF and pre-emptive plerixafor (PEF) is becoming increasingly popular. Until few years back, cost of PEF was prohibitive thereby limiting its use and prompting a search for alternative cheaper drugs. Mouse models have shown that Proteasome Inhibitors aid in hematopoietic stem-cell (HSC) mobilization by down-regulating very-late antigen-4 (VLA-4) on bone marrow stromal cells which interacts with vascular cell adhesion molecule (VCAM-1) on HSC. We previously reported that bortezomib (Bort) in combination with Cy-G-CSF showed a trend towards higher CD34 yield and reduced need for apheresis sessions, without additional toxicity. There is limited data comparing mobilization regimens, especially from low-middle income countries where HSC collection may not be done after 4-6 cycles of first-line therapy. We hereby report our 15-year experience of various mobilization regimens for MM. Methods All patients with MM who underwent HSC mobilization from September 2007 - December 2022 were included in this analysis. Various mobilization regimens [Group 1 - G-CSF + Bort (August 2018 - December 2022); Group 2 - G-CSF + plerixafor (August 2018 - December 2022); Group 3 - Bort-Cy-GCSF (April 2016 - July 2018); Group 4 - Cy + G-CSF (September 2007 - March 2016)] were used as per respective time-periods (Table 1). Our aim was to collect CD34 cell dose of 5million/kg to suffice for 2 transplants. G-CSF (5 mcg/kg subcutaneously BD) was given on days 1-5 (Groups 1 and 2). Bort (1.3mg/m 2 iv / sc) (Group 1) or PEF (Group 2) were given on day 4 twelve hours prior to planned apheresis on day 5. Apheresis was done on day 5, and additionally on day 6, if first harvest was inadequate for 2 transplants. In group 3, Bort (1.3mg/m 2 iv) was given on days-1,4,8,11, with Cy (1gm/m 2 iv) on days 8 and 9, followed by G-CSF from day 11 onwards. Cy (1gm/m 2 iv) was given on day 1 and 2 (Group 4), followed by G-CSF from day 4 onwards. Stem cell harvest was done in groups 3 and 4 once peripheral blood CD34 (PB CD34) was &amp;gt;20/µL. In groups 3 and 4, if PB CD34 was &amp;lt;20/µL for 2 subsequent days, PEF was used according to physician's discretion, if available. Similarly in Group 1, if PB CD34 was between 10-20/µl on day 4, PEF was used according to physician's discretion. PEF was used in any group after the first harvest if the cell dose was deemed inadequate, at physician's discretion. Primary objective was to determine proportion of patients with CD34 + dose ≥5x10 6/kg in first apheresis in various groups. Secondary objectives were to determine total median CD34 + dose (x10 6/kg) collected, median CD34 + (x10 6/kg) in first apheresis, and frequency of mobilization failure. Mobilization failure was defined as total collected CD34 + dose of &amp;lt;2x10 6/kg or abandoned harvest attempt anticipating a poor collection.Analysis was done as per planned regimen (intention to treat analysis). Results Total 205 patients were analyzed. Median age was 48 years (27-65 years) and 143 (70%) were males (Table 1). Median day of first collection in groups 3 and 4 was day10 from the first dose of cyclophosphamide. Percentage of patients who collected ≥5x10 6 CD34 + cells/kg in first apheresis were 26%, 53%, 69% and 63%, respectively in Groups 1-4 (p=0.0001) (Table 1). CD34+ cell-dose in first apheresis and total dose collected are shown in Table 1. In comparison to groups 1 and 2, both chemo-mobilization groups (group 3 and 4) had a significantly higher total cell dose (Figure 1). In comparison to group 1, both Cy chemo-mobilization groups had a significantly higher cell dose in first harvest, but there was no significant difference between group 2 and group 4 (p=0.23) (Figure 1). PEF was required additionally in 47%, 22%, and 7% of patients in groups 1, 3 and 4 respectively (P&amp;lt;0.00001). Amongst transplanted patients, there was no difference in neutrophil or platelet engraftment and the frequency of engraftment syndrome in various groups. Conclusion Cy-based chemo-mobilization regimens have advantage of higher total stem cell yield, while they are equivalent to G-CSF + Plerixafor for harvest in single apheresis. Addition of Bortezomib to Cyclophosphamide may help to increase stem cell yield.

Second stem cell transplantation for treatment of relapsed/refractory multiple myeloma after first autologous stem cell transplant: A 15-year retrospective institutional analysis.

Multiple myeloma remains an incurable disease, with the majority of patients relapsing after autologous stem cell transplant (ASCT). After relapse, second transplant remains one of the therapeutic options, along with novel agents. We reviewed the data of our patients who underwent ASCT for myeloma (N = 202) over the last two decades (2004-2019). Of these, 12 patients underwent a second transplant. Out of 12 patients, nine underwent second autologous stem cell transplant, whereas three received an allogeneic stem cell transplantation (Allo-SCT). Median progression-free survival (PFS) after the first ASCT was 32 months (5-84 months). Median interval between both the transplants was 35 months (4-159 months). Median age of our cohort which underwent second transplant was 56 years. Overall response rate (ORR) post-second transplant on day +100 was 83.3%, without any transplant-related mortality (TRM). With the use of preemptive plerixafor, none of our patients required a second day for stem cell harvest. Median CD34 dose of stem cells infused was 4.11 × 106/kg. Similar to the first ASCT, the median time to neutrophil and platelet engraftment was 11 and 12 days, respectively. At a median follow-up of 41 months, estimated 3-year PFS and overall survival (OS) was 37% ± 15% and 63% ± 15%, respectively. ">Among all relapsed myeloma patients who were transplant eligible, 11% underwent a second transplant. Second transplant is well tolerated with similar time to engraftment after first ASCT. Hence, we believe that second transplant is a feasible, cost-effective option in a resource-limited setting, which should be more widely utilized.

Stem Cell Mobilization Characteristics for Transplant Eligible Patients with Newly Diagnosed Multiple Myeloma (NDMM) Treated with Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab (KRd-Dara)

Introduction: CD38 monoclonal antibody (mAb)-containing quadruplet regimens have been shown to improve depth and duration of response in patients with NDMM eligible for autologous stem cell transplant (ASCT). However, some studies have raised concerns about the detrimental effect of combined lenalidomide and CD38 mAbs on stem cell mobilization. As an exploratory endpoint, we evaluated the effect of KRd-Dara on stem cell mobilization and collection in the Levine Cancer Institute (LCI) KRd-Dara study (NCT04113018) that permits up to 8 cycles of induction with KRd-Dara followed by an MRD-directed treatment algorithm for transplant-eligible and transplant-noneligible patients (Bhutani et al, Blood 2020 Abstr 1388). We provide a table summarizing our results from stage 1, along with two other phase II studies, the MANHATTAN (Landgren et al, JAMA Oncol 2021) and the MASTER (Costa et al, JCO 2021) studies that used variable numbers of KRd-Dara induction cycles prior to stem cell apheresis. Patients and study design: Eligible patients had NDMM and an ECOG performance status score of 0-2. Induction treatment consisted of 28-day cycles of KRd-Dara with intravenous carfilzomib, 20/56 mg/m2 (days 1, 8, and 15); lenalidomide orally, 25 mg (days 1-21); dexamethasone weekly; daratumumab (subcutaneous) per standard approved dosing schedule. One pre-study cycle with non-protocol therapy was allowed. During stage I of the study, stem cell collection for transplant-eligible patients was performed after 8 cycles of induction. All patients were mobilized with granulocyte-colony stimulating factor (G-CSF, 10 µg/kg) daily for 5 days. Preemptive Plerixafor was administered in the evening of Day 4 if the blood CD34+ cell count was <50/µl. Collection was done over 2 days in some patients who failed to collect sufficient CD34+ cells during the first day. A second mobilization attempt after a few weeks of additional wash-out was allowed. Our center-specific minimum required collection target is 3 x 106 CD34+ cells/kg, below which the stem cell dose is considered inadequate to perform a single ASCT. Physicians requested collection for potentially 2 or 3 transplants per patient, with a collection goal of 8 -12 x 106 CD34+ cells/kg. Mobilization failure was defined as the proportion of patients with Day 4 CD34 count <1/µl or collection of <3 x 106 CD34+ cells/kg (considered inadequate for even one ASCT) during the first mobilization attempt. Results: Among the 22 mobilized patients during stage 1 analysis, the median age was 60 years (range, 34 to 72) and 32% were African Americans. Eighteen patients received plerixafor, 3 did not based on futility as their Day 4 blood CD34 count was zero, and only one patient met the threshold of not receiving Plerixafor. The median total CD34+ cells collected were 7.73 x 106/kg (range, 0.00-19.18). Six (27%) patients had mobilization failure after their first attempt. Four of these patients underwent a second attempt after a median of 56 days (range, 36-98 days), with only one patient collecting enough CD34+ cells for one ASCT. Of the 10 patients whose collection goal was 2 transplants (8 million CD34 cells/kg), 9 patients did not meet the goal. Of the 12 patients whose collection goal was 3 transplants (12 million CD34 cells/kg), 8 patients did not meet the goal. Conclusions: The stem cell mobilization failure rate was high in patients collecting after 7 or 8 cycles KRd-Dara. Second remobilization with G-CSF and plerixafor was successful in only 1 of the 4 patients. We have modified stage 2 of the protocol to allow stem cell collection after cycle 3 of KRd-Dara induction. We plan to do combined analyses of LCI, MANHATTAN and MASTER to determine predictive factors associated with poor stem cell mobilization after KRd-Dara induction. Based on our results, we recommend stem cell collection after 3-4 cycles of KRd-Dara regimen. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P932: ON-DEMAND PLERIXAFOR WITH CYCLOPHOSPHAMIDE AND G-CSF FOR HEMATOPOIETIC STEM-CELL MOBILIZATION IN MULTIPLE MYELOMA PATIENTS: FINAL RESULTS OF THE MOZOBL06877 STUDY

Background: High-dose melphalan and autologous stem-cell transplant (ASCT) are pillars for the upfront treatment of ASCT-eligible newly diagnosed multiple myeloma (ND)MM patients (pts) or as salvage strategy at relapse. Failure to collect an adequate number of hematopoietic stem cells (HSC) to receive ASCT (<2×106 CD34+ cells/kg) occurs in 5%-15% of MM pts undergoing HSC mobilization with granulocyte colony-stimulating factor (G-CSF) or G-CSF+cyclophosphamide (G-CSF/CY). Aims: We report the final results of the observational MOZOBL06877 study (NCT03406091; partially supported by Sanofi investigation funds) to prospectively assess the performance of HSC mobilization with G-CSF/CY plus on-demand CXCR4 inhibitor plerixafor (PLX) in NDMM pts treated with novel agents. Methods: NDMM pts undergoing HSC mobilization with CY (2-4 g/m2) and G-CSF (5-10 mcg/kg/day) were enrolled and observed up to 30 days after mobilization. According to its label, “on-demand” PLX was administered in pts with <20 CD34+ cells/ul after ≥4 days of G-CSF or in case <1×106 CD34+ cells/kg were collected on the first apheresis day. Pts gave written informed consent. The primary endpoint was the poor mobilizer rate, defined as the rate of pts collecting <2×106 CD34+ cells/kg or requiring PLX. Secondary endpoints were the identification of predictive factors for PLX use and safety during mobilization. Results: 301 NDMM pts were enrolled and analyzed; 72% received induction with bortezomib-thalidomide-dexamethasone, 9% a lenalidomide (Len)-based and 3% a daratumumab (Dara)-based regimen. Overall, 48 pts (16%) were poor mobilizers: 14 (5%) failed to yield ≥2×106/Kg CD34+, while 34 (11%) required rescue with PLX. Among pts yielding <2×106/Kg CD34+ cells, 4 received PLX, while 10 did not. Among pts who successfully collected ≥2×106/Kg CD34+ (n=287, 95%), 34 (12%) required PLX: 23 (68%) due to a CD34+/uL count ≤20 after ≥4 days of G-CSF and 11 (32%) to a collection <1×106/Kg after the first apheresis day. In pts mobilized with PLX, median number of CD34+×106/L cells increased from 17.5 (IQR 10.8-25.6) before PLX to 58.3 (IQR 34.2-100.2) after PLX. Median number of CD34+/Kg collected in pts who did not require PLX was 10.2×106 (IQR 8.3-13.2). In pts who required PLX, a median of 6.5×106 CD34+/Kg (IQR 4.6-9.6) was collected. An adequate HSC yield for ≥2 ASCTs (≥4×106/Kg) was obtained in 96% and 85% of pts not receiving or receiving PLX, respectively. Median number of apheresis days was 1 (IQR 1-2) in pts not requiring PLX and 2 (IQR 1-2) in pts requiring PLX. In a multivariate analysis (Table), factors predicting PLX use were advanced disease stage (R-ISS 3 vs 1-2, OR 5.5, P=0.01), bone marrow (BM) plasma cell (PC) infiltration at diagnosis (PC>60% vs ≤60%, OR 4.2, P<0.001), pre-mobilization absolute neutrophil count (ANC, < vs >2500/mmc, OR 2.8, P=0.01), and the use of Len-based (Yes vs No, OR 3.4, P=0.02) or Dara-based induction regimens (Yes vs No, OR 5.3; P=0.04). Grade 3 infections occurred in 3 pts (1%), with no grade 4-5 reported. Image:Summary/Conclusion: Among NDMM pts treated with novel-agent-based induction and undergoing HSC mobilization with CY/GCSF, “on-demand” PLX in case of low CD34+ cell count or insufficient HSC yield was a safe and effective rescue strategy, reducing mobilization failure from 16% to 5%. Predictive factors for PLX use were advanced disease stage, high BM plasmacytosis, low ANC values before mobilization and the use of Len/Dara during induction. Preemptive PLX in pts with ≥1 risk factors should be investigated to further reduce the risk of mobilization failure.

Autologous peripheral blood stem cell mobilization and collection in patients with lymphoma and multiple myeloma: A single-center experience using the plerixa for pre-emptive approach.

Objectives:To review and assess the efficiency of pre-emptive plerixafor administration for poor mobilization (PM) and to review and assess mobilization efficiency (≥2×106 CD34+ cells/kg) in patients who received autologous stem cell transplantation for lymphoma and multiple myeloma (MM) at the Department of Adult Hematology/Blood Marrow Transplant, Princess Noorah Oncology Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia, over the past 7 years.Methods:This retrospective study evaluated all patients with MM and lymphoma undergoing peripheral blood stem cell mobilization and collection at our institution between February 2014 and August 2021. Plerixafor was administered pre-emptively by a plateau of <10 peripheral blood CD34+/µl after chemotherapy-based mobilization or CD34+ of <8/µL on day 4 after mobilization with G-CSF alone. Between peak CD34+ levels of 10-15/µl, plerixafor will be used at the discretion of the treating physician.Results:In total, 215 patients were enrolled. Among them, 80% had peak CD34+ level ≥20/µL, 11% had clear poor mobilization (peak CD34+ levels <10/µL), and 9% had borderline PM (CD34+ between 10-19/µL). Plerixafor was administered pre-emptively in 13% of the patients and 75% of patients with borderline PM were collected without plerixafor, suggesting that plerixafor is not needed if CD34+ >15/µL on the anticipated collection day. Mobilization failed in only one patient (<1%).Conclusion:Our data showed that with plerixafor pre-emptive administration, the primary endpoint was achieved for most patients identified with PM, preventing the need for a second mobilization attempt.

MM-400: Plerixafor and Granulocyte Colony-Stimulating Factor for Poor Mobilizers in Patients Undergoing Autologous Peripheral Hematopoietic Stem Cell Transplant: Single-Institution Study

Context Autologous hematopoietic stem cell transplant (ASCT) has become the mainstay treatment for many hematological malignancies and solid tumors. An adequate number of stem cells must be collected for better ASCT outcomes, which is challenging in 5%–30% of patients. To improve mobilization, plerixafor is used, along with granulocyte colony-stimulating factor. Objective To evaluate the real-life efficacy of plerixafor and to identify factors associated with poor mobilization. Design and Setting This is a retrospective, single-center study involving patients who received plerixafor pre-ASCT between January 2013 and December 2020 at a tertiary care center in Lebanon. Patients We identified a total of 72 consecutive adult patients. Patients who received plerixafor were divided into two groups: poor mobilizers with pre-emptive use before first apheresis for those with peripheral CD34+ stem cells (PSC) 20 cells/µL. Main Outcome Measures The main endpoints were to evaluate characteristics of poor mobilizers, stem cell yields pre- and post-plerixafor, as well as the time to neutrophil and platelet engraftment. Results The median age at diagnosis was 54 years (12–73). 60% were males. 50 (70%) patients had multiple myeloma (MM), 12 (15%) had non-Hodgkin lymphoma, 7 (10%) had Hodgkin lymphoma, and 3 (4%) had solid tumors and Waldenstrom macroglobulinemia. The median follow-up was 9 months (1–59). 59 (82%) patients had low PSCs, requiring pre-emptive plerixafor prior to apheresis. 62% of MM and 54.5% of non-MM patients needed >1 collection. 97% of all patients collected CD34+ >2×106cells/kg post-plerixafor. The median collected final CD34+ cells post-plerixafor was 4.4×106/kg (1.84–18.62). Factors associated with poor mobilization were male gender, age at diagnosis >55 years, MM, and bone marrow involvement (p=0.041, p=0.031, p=0.04, and p=0.012, respectively). Median times to absolute neutrophil count (ANC) and platelet engraftment were 11 (4–26) and 17 (4–28) days, respectively. A longer ANC engraftment (>2 weeks) was observed in patients who were infused Conclusion These results can guide us to use plerixafor early in selected patients who are predicted to fail mobilization.

Peripheral stem cell mobilization strategies in patients with autologous hematopoietic cell transplantation: A single center's experience

This research is to investigate the parameters which may affect the mobilization of stem cells in patients receiving autologous hematopoietic peripheral blood stem cell transplantation (PBSCT). A retrospective study was carried out using the data derived from the medical files of 242 patients who received PBSCT. Descriptive, clinical, and laboratory parameters were compared between patients with successful and unsuccessful stem cell mobilization. Successful stem cell mobilization ratio was 4.463 times higher when preemptive plerixafor was administrated; 1.032 times higher when CD34+ cell count increased 1 unit at the beginning of mobilization. The white blood cell count was inversely correlated with the success of mobilization. An increase of 1 unit in WBC count was associated with a 1.027 times decrease in the success rate. The data indicated that the administration of preemptive plerixafor and CD34+ cell count at the beginning of mobilization were directly related to the success of mobilization after PBSCT. On contrary, WBC count was inversely associated with the success rate.

Outcomes of GCSF and Pre-Emptive Plerixafor Based Peripheral Blood Stem Cell Mobilization Among Patients with Multiple Myeloma-Experience from Newly Established Transplant Unit in Eastern Mediterranean Area

Introduction Granulocyte Colony Stimulating Factor (GCSF) with cyclophosphamide based peripheral blood stem cell (PBSC) mobilization is a widely used strategy among patients with multiple myeloma (MM), however, it is associated with toxicity and morbidity including severe infectious complications needing hospitalization. Plerixafor with GCSF has been widely used for mobilization as a preemptive strategy or during second attempt at collection with encouraging results. Methods We describe our experience from a newly established transplant unit in the Eastern Mediterranean region. A retrospective chart review was done and all consecutive patients of MM who underwent PBSC mobilization by GCSF and plerixafor between 2017 to 2020 were included in the study. Patients received GCSF (filgrastim, 10 µg/kg/day) and if peripheral blood CD34 count was less than 20/µl on day 4, patients received the first dose of plerixafor (240 µg/kg/day) on the evening of Day 4. Daily apheresis started on Day 5 for a maximum of 4 days, or until enough stem cells collected for one or two transplants at physician's discretion. Results A total of seventeen PBSC collections were carried out among patients with myeloma (n=17). There were 10 males and 7 females. The median age was 53 years (range 38-71), and 8/17 were less than 50 years of age. 14/ 17 were of IgG myeloma subtype, 2/17 were light chain myeloma, 1/17 was IgA myeloma type. 6/17 patients had R-ISS stage 3 disease while rest (11/17) had R-ISS stage 2 disease. 15/17 patients were in first remission. Only 1/17 patients had high-risk cytogenetics. 12/17 patients had bortezomib based therapy while 5/17 had lenalidomide based therapy. 13/17 patients had GCSF alone mobilization while 4/17 had GCSF plus pre-emptive plerixafor. 9/17 had a single collection while 8/17 had 2 collections. All patients on plerixafor needed two collections. Median CD34 stem cell dose was 8.6 x10^6 cells/kg (range 3.4-20 x 10^6 cells/kg). No grade 2-4 adverse events were recorded with this strategy post-collection and none required hospitalization for any adverse events. All patients underwent melphalan based conditioning and autologous stem cell transplant, although only 12/17 received a full dose of 200 mg/m2. 13/17 patients had fresh stem cells infused while the rest had cryopreserved stem cells. Median time to neutrophil recovery was 11 days (range 9-27) while median time to platelet recovery was 12 days (range 10-37). Day 100 mortality was zero percent. Conclusions Our study demonstrates successful collection with high stem cell yield enough for two stem cell transplants with GCSF and preemptive plerixafor strategy, in patients with MM, thus saving patients toxic effects of cyclophosphamide including cytopenias, infections which at times are severe causing morbidity and mortality. Over two-thirds of patients collected with GCSF alone. No major adverse events post stem cell collection were noted and all our patients engrafted early thus reducing hospital stay. Although the use of plerixafor increases cost but failure of mobilization, second mobilization, and infections (at times severe), delayed engraftment have their own costs and implications. Our study at our new transplant unit confirms that this pre-emptive strategy is safe, effective and reasonable chemo free first line option with no major adverse events as demonstrated by other studies. Disclosures No relevant conflicts of interest to declare.

A Novel Hematopoietic Progenitor Cell Mobilization Regimen Comprising Bortezomib, G-CSF, and Preemptive Plerixafor for Multiple Myeloma.

Adequate hematopoietic progenitor cell collection is critical for autologous peripheral blood stem cell transplantation. Conventionally, patients with multiple myeloma are treated with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) or G-CSF alone to mobilize their peripheral blood stem cells. However, some patients exhibit insufficient stem cell recruitment in response to these regimens. Recently, plerixafor has been approved for coverage by insurance in Japan. Combination treatment with plerixafor and G-CSF is now a standard procedure. In addition, treatment with bortezomib and G-CSF results in efficient stem cell recruitment. On the basis of the results from mouse studies, we hypothesized that combination treatment with bortezomib ensures efficient mobilization and mediates in vivo purging of malignant cells. Therefore, we administered a regimen of bortezomib, G-CSF, and preemptive plerixafor to 10 patients with multiple myeloma, and analyzed its efficacy and safety. The median patient age was 68 years. We collected CD34-positive cells (median: 4.9×106/kg) in a single session of apheresis from all patients. We observed no obvious myeloma cell contamination in the collected product or serious toxicity during treatment and collection. After collection, we performed autologous peripheral blood stem cell transplantation and confirmed engraftment in all patients (median: day 10). We found that the regimen is safe and reliably facilitated the collection of sufficient autologous peripheral blood stem cells by apheresis from all patients in a single day. Despite the small patient group size, we conclude that the regimen is promising for safe and efficient collection of peripheral blood stem cells for autologous transplantation in patients with multiple myeloma.

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.

Preemptive plerixafor based mobilization strategy in multiple myeloma patients for autologous stem cell transplantation

Optimum mobilization of CD34+ve cells following G-CSF is critical for engraftment in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). Approximately 10% of patients are poor mobilizers. We compared use of pre-emptive plerixafor based on day 4 circulating CD34+ve cells with patients mobilized with G-CSF alone.

Clinical and cost outcomes of pre-emptive plerixafor administration in patients with multiple myeloma undergoing stem cell mobilization

PurposeThe stem cell mobilization agent plerixafor significantly improves CD34+ stem cell procurement in patients with multiple myeloma undergoing autologous stem cell transplant. We compared mobilization success rates and costs of two regimens of plerixafor administration: pre-emptive (P-PL, initiated the evening prior to the first day of stem cell collection) and standard (S-PL, initiated the evening prior to the second day of stem cell collection in the event of inadequate collection on the first day). MethodsPatients with multiple myeloma undergoing mobilization were categorized as either P-PL or S-PL. Stem cell collection success was evaluated using logistic regression models. Associated costs were aggregated in terms of average collections per patient in each mobilization option (patient level), and escalated to a panel of 5000 patients (population level). Results299 patients were evaluable; 241 received P-PL and 58 received S-PL. Patients receiving P-PL had higher median CD34+ count pre-collection and higher median total CD34+ cell harvest on the first collection (6.75 × 106/kg for P-PL, 1.96 × 106/kg for S-PL; P<0.01). In multivariable analyses, P-PL remained significantly associated with the ability to collect ≥2 × 106/kg CD34+ on the first day (OR = 4.05, 95% CI, 1.19–13.83, P = 0.03) and ≥5 × 106/kg CD34+ in total (OR = 3.09, 95% CI, 1.04–9.23, P = 0.04). P-PL saved $11,248 (46%) per patient compared with S-PL. ConclusionP-PL significantly enhanced collection efficiency, with most patients completing collection in 1 day, resulting in substantial cost savings.

Pre-Apheresis Peripheral Blood CD34+ Cell Count Obviates Need for Pre-Emptive Plerixafor in Half of Patients Undergoing Stem Cell Mobilization.

Success and safety of autologous stem cell transplant (ASCT) is contingent on collecting enough CD34+ cells. CXCR4 antagonists (plerixafor) can increase the success and efficiency of stem cell mobilization. Plerixafor has been increasingly used but concerns remain about its cost and logistics of administration. We report our experience with plerixafor administration based on pre-apheresis peripheral blood (PB) CD34+ cell counts. We retrospectively reviewed consecutive patients who underwent stem cell mobilization and transplant at our center between 07/2012 and 06/2018. Patients with incomplete records were excluded. PB CD34+ cell counts were obtained daily starting the day before apheresis. Target yield was 5 × 10^6 CD34+ cells/kg with a minimum of 2 × 10^6 CD34+ cells/kg being acceptable. Lymphoma patients were mobilized primarily after chemotherapy whereas patients with plasma cell disorders were mobilized with steady state G-CSF. Plerixafor was pre-emptively given when PB CD34+ cell count was ≤20 cells/uL. Repeat plerixafor dosing was per provider preference. Median [IQR] is reported, and t-tests or Wilcoxon Rank-Sum tests were used for continuous variables whereas n (%) is reported, and Chi-Square/Fisher Exact tests were used for categorical variables. A total of 132 patients were included. 50.8% were given plerixafor pre-emptively (Pre-emptive group, n=67) and 49.2% were not (non-pre-emptive group, n=65). 13 patients in the non-pre-emptive group subsequently received plerixafor. Median pre-apheresis PB CD34+ cell count (cell/uL) was 11.22 in the pre-emptive group (before plerixafor administration) and 42.99 in the non-pre-emptive group. Overall, 11 patients (8.3%) required a second mobilization and 40 patients (30.3%) successfully reached target yield after 1 apheresis session without plerixafor use. No difference was noted between both groups in age (p=0.45), gender (p=0.16), mobilization method (p=0.063), primary diagnosis (p=0.571), mobilization attempts (p=0.53), number of apheresis sessions (p=0.72) and CD34+ cell yield (p=0.70). Total number of plerixafor doses was significantly lower in the non-pre-emptive group (p In summary, dosing plerixafor based on pre-apheresis PB CD34+ cell counts allows for a high success rate on the first mobilization attempt while minimizing plerixafor use.

Bendamustine Adversely Affects Stem Cell Mobilization Among Patients with Mantle Cell Lymphoma (MCL): A Comparison of the BR Vs RCHOP Eras in British Columbia (BC), Canada

IntroductionIn 2013, bendamustine/rituximab (BR) replaced RCHOP as standard first line treatment for both transplant eligible and ineligible MCL patients (pts) in BC. Retrospective cohort studies report that bendamustine has no adverse effect on peripheral blood stem cell (SC) mobilization but this is discordant with local experience. We sought to compare rates of failed SC collection in MCL pts planned for high dose chemotherapy and autologous stem cell transplant (ASCT) after BR or RCHOP and identify risk factors for failed SC mobilization and collection.MethodsWe identified all pts with MCL in BC treated with BR or RCHOP as first line therapy who underwent SC mobilization from Jan. 1 2003-Dec. 31 2017 using the Leukemia/Bone Marrow Transplant Program of BC and Apheresis Database Standard mobilization was with G-CSF alone (G) until difficulties with SC collection were noted after BR. Different mobilization strategies were then used, including delaying SC collection 2-3 mos after BR, G + cyclophosphamide (G+C) mobilization and/or “rescue” plerixafor if Day 1 SC collection was inadequate. Failure of SC collection was defined as yield <1 x106 CD34+ cells/kg on apheresis Day 1 (D1fail). . All variables significant in univariate analysis (P<0.1) were entered into a multivariate analysis (MVA) logistic regression model to identify factors associated with D1 fail.ResultsA total of 152 pts were identified. 2 were excluded as they had pre-emptive plerixafor prior to apheresis D1 on a trial. Of the remaining 150 pts, 55 (37%) received BR, 95 (63%) RCHOP for a median of 6 cycles (range 1-6). Baseline characteristics were similar between groups (Table 1). Pts receiving BR had higher remission rates compared to RCHOP (CR 58% vs 35%, P=.004) and a longer duration from their last chemotherapy to apheresis D1 (BR 89 d vs RCHOP 39 d, P<0.), reflecting an intentional change in practice. For this same reason, use of G+C mobilization was higher in BR pts (45%) compared with RCHOP pts (1%).Failure on D1 of SC collection was significantly higher after BR compared to RCHOP (45% vs. 10%, P<.001). This difference persisted when only pts mobilized with G alone were included: D1fail 60% BR vs 10% RCHOP (P<.001), Fig. 1. Among BR pts, D1fail was higher for those mobilized with G compared with G+C (60% vs. 28%, P=.03).Of the 25 BR pts with D1fail, 20 pts received rescue plerixafor (P) (1 dose: 18, 2 doses: 1, 3 doses: 1) with 17 successfully collecting > 2.0 x106 CD34+ cells/kg, 2 successfully collected after a 2nd round of SC mobilization (Pt1: G+C+P, Pt2: G+P), and 1 pt did not undergo ASCT due to collection failure. Of the 5 pts who did not receive plerixafor, 2 successfully collected with 1-2 additional apheresis days and 3 successfully collected with a 2nd round of SC mobilization (2: G+P, 1: G+C). Among the 9 RCHOP pts with D1fail, 1 had rescue plerixafor with success, 3 successfully collected after 1-2 more apheresis days and 5 had a 2nd round of SC mobilization (1: G, 4: G+P), of which 1 failed and did not proceed to ASCT.Univariate analysis identified the following associated with D1fail: frontline therapy (BR vs RCHOP, P=<.001), mobilization regimen (G+C vs G, P=.001), gender (P=.002) and D1 platelet count (P=<.001). Delaying SC mobilization in pts who received BR did not improve D1 yield (P=.31). In MVA, frontline therapy with BR had an increased risk of D1fail compared to RCHOP with an odds ratio (OR) of 7.83 (95% CI 2.7-23.1), P<.001. Using G+C significantly improved the odds of a successful collection compared to G alone (OR for D1fail 0.17 [95% CI 0.05-0.62], P=.007). Female gender and low platelet count also increased risk of D1fail in MVA (Table 2).ConclusionMCL pts who receive BR as first line therapy have an almost 8-times higher risk of failure of D1 SC collection compared to those who receive RCHOP. This failure can be overcome largely with “rescue” plerixafor and partially with planned G+C mobilization such that successful collection can be achieved in >90% of pts. However, these agents add cost and potential toxicity. Platelet count on D1 SC collection is a potential indicator of high risk of failure. Delaying SC mobilization in BR pts does not improve collection yield. The impact of bendamustine in pre-transplant chemotherapy regimens, not only for MCL but also for a broad range of lymphomas where it is being increasingly used, must be considered when planning SC mobilization strategies. [Display omitted] DisclosuresSehn:Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

Poor mobilizer and its countermeasures

Mobilization failure is a major concern in patients undergoing hematopoietic cell transplantation, especially in an autologous setting, as almost all donor harvests can be accomplished with granulocyte-colony stimulating factor (G-CSF) alone. Poor mobilizers, defined as those with a peripheral blood CD34+ cell count ≤20 cells/μl after mobilization preceding apheresis is a significant risk factor for mobilization failure. We recommend preemptive plerixafor plus G-CSF (filgrastim, 10 μg/kg daily) as a first mobilization strategy, which yields sufficient peripheral blood progenitor cells (PBPCs) in almost all patients and avoids otherwise unnecessary remobilization. Preemptive plerixafor is administered in patients with a day-4 peripheral blood CD34+ count <15, depending on the disease and the target PBPC amount. Cyclophosphamide is reserved for patients who fail the first PBPC collection. We recommend second mobilization for patients who could not achieve a sufficient PBPC amount with the first mobilization. In these patients, a second attempt with plerixafor plus G-CSF or mobilization with plerixafor in combination with cyclophosphamide and G-CSF is recommended. Increased dose and/or twice daily administration of G-CSF can be considered.

Plerixafor in non-Hodgkin\u2019s lymphoma patients: a German analysis of time, effort and costs

Mobilization and collection of peripheral blood stem cells is part of the standard treatment procedure for non-Hodgkin’s lymphoma patients eligible for high-dose chemotherapy with autologous stem cell transplantation. Mobilization is usually achieved with chemotherapy and/or cytokines, but plerixafor might be added in case of poor mobilization. Due to the high cost several institutions have developed their own management pathway to optimize use of plerixafor. Such models are however rarely generalizable; in a multi-center, European, non-interventional study, evaluating the impact of plerixafor in poor mobilizers, country specific differences in patient treatment and cost structure were obvious. For German centers, there was a non-significant reduction in the number of apheresis sessions carried out and in apheresis costs. In contrast to other European countries the majority of German Plerixafor patients were very poor mobilizing patients with initial CD34+ cell count ≤ 10/µl (40/51). In this group the number of apheresis sessions decreased from 2.1 to 1.6 sessions per patient (p = 0.01) and costs decreased from €6246 to €4758 (p = 0.01). Our results show that preemptive plerixafor use has a strong effect in poor mobilizers with an initial CD34+ cell count ≤ 10 cells/µl.

Platelet Count before Peripheral Blood Stem Cell Mobilization Is Associated with the Need for Plerixafor But Not with the Collection Result

Background: A low platelet count before mobilization has recurrently been identified as risk factor for poor mobilization. Methods: To determine the relevance of this finding for peripheral blood stem cell (PBSC) mobilization, including pre-emptive or rescue plerixafor in the case of poor mobilization, we retrospectively analyzed all patients undergoing PBSC collection at our institution between January 2014 and December 2015 (n = 380). Results: In total, 99% of the patients (377/380) successfully collected a minimum of 2 × 10⁶ CD34+ cells/kg body weight sufficient for a single transplant. Rescue or pre-emptive plerixafor was administered to 11% of the patients (42/380). No correlations between the platelet count before mobilization and the number of peripheral blood CD34+ cells or the CD34+ cell collection result were detected in the entire population or the subgroups according to diagnosis (newly diagnosed multiple myeloma, relapsed multiple myeloma, lymphoma, amyloid light-chain amyloidosis, sarcoma, or germ cell tumor). However, patients requiring pre-emptive or rescue plerixafor had a significantly lower platelet count before mobilization (217/nl vs. 245/nl; p = 0.004). Conclusion: With the current state of the art PBSC mobilization strategies, the platelet count before mobilization was not associated with the CD34+ cell collection result but was associated with the need for pre-emptive or rescue application of plerixafor.

Preemptive plerixafor injection added to pegfilgrastim after chemotherapy in non-Hodgkin lymphoma patients mobilizing poorly.

Filgrastim is usually combined with chemotherapy to mobilize hematopoietic progenitor cells in non-Hodgkin lymphoma (NHL) patients. Limited information is available on the efficacy of a preemptive plerixafor (PLER) injection in poor mobilizers after chemotherapy and pegfilgrastim. In this prospective study, 72 patients with NHL received chemotherapy plus pegfilgrastim, and 25 hard-to-mobilize patients received also PLER. The usefulness and efficacy of our previously developed algorithm for PLER use in pegfilgrastim-containing mobilization regimen were evaluated as well as the graft cellular composition, hematological recovery, and outcome after autologous stem cell transplantation (auto-SCT) according to the PLER use. A median 3.4-fold increase in blood CD34+ cell counts was achieved after the first PLER dose. The minimum collection target was achieved in the first mobilization attempt in 66/72 patients (92%) and 68 patients (94%) proceeded to auto-SCT. An algorithm for PLER use was fulfilled in 76% of the poor mobilizers. Absolute numbers of T-lymphocytes and NK cells were significantly higher in the PLER group, whereas the number of CD34+ cells collected was significantly lower. Early neutrophil engraftment was slower in the PLER group, otherwise hematological recovery was comparable within 12months from auto-SCT. No difference was observed in survival according to the PLER use. Chemotherapy plus pegfilgrastim combined with preemptive PLER injection is an effective and convenient approach to minimize collection failures in NHL patients intended for auto-SCT. A significant effect of PLER on the graft cellular composition was observed, but no difference in outcome after auto-SCT was detected.