Autologous Stem Cell Mobilization Research Articles

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

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

Pushing the limits of successful mobilization of autologous hematopoietic stem cells

Pushing the limits of successful mobilization of autologous hematopoietic stem cells

Comparison of etoposide combined with G-CSF and cyclophosphamide combined with G-CSF in mobilization of autologous peripheral hematopoietic stem cells in patients with newly diagnosed multiple myeloma

Comparison of etoposide combined with G-CSF and cyclophosphamide combined with G-CSF in mobilization of autologous peripheral hematopoietic stem cells in patients with newly diagnosed multiple myeloma

Successful Mobilization of Autologous Hematopoietic Peripheral Blood Stem Cells after Salvage Chemotherapy in Patients with Low CD34 Blood Cell Counts

A major barrier for proceeding to autologous stem cell transplantation (ASCT) is an inability to mobilize and collect an adequate number of peripheral blood (PB) stem cells (PBSC) for the transplant graft. Plerixafor added to granulocyte colony stimulating factor (G-CSF) alone, without prior chemotherapy, significantly improves the mobilization of autologous PBSC in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). However, the efficacy of plerixafor and the best timing to give the drug to poorly mobilizing patients with very low PB CD34+ cell counts after salvage chemotherapy and G-CSF are not well defined. We hypothesized that PBSC mobilization and collection might be improved in heavily treated patients who mobilized very poorly after salvage chemotherapy and G-CSF by alternating the days of plerixafor administration and leukapheresis. A day of rest between plerixafor doses, while continuing G-CSF, could allow time for some replenishment of the marrow stem/progenitor cell pool before the next mobilization. A retrospective review of collection results in poorly mobilizing patients at our center was undertaken. Three cohorts were identified: those who got every-other-day plerixafor and leukapheresis, those who got sequential plerixafor and leukapheresis and those who got risk adapted plerixafor. Overall, 69% of patients with NHL and MM with PB CD34+ cell counts <5/µL after salvage chemotherapy and G-CSF were ultimately able to collect adequate CD34+ cells to support ASCT using daily plerixafor and leukapheresis. On the alternating plerixafor and leukapheresis schedule, all 17 patients achieved the cumulative CD34+ cell product goals required for ASCT. This positive observation after salvage chemotherapy and G-CSF led to the incorporation at our center of an alternate-day schedule of plerixafor and leukapheresis into our real-time risk adapted strategy for poor mobilizers.© 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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.

Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis, the Ottawa Protocol.

Autologous hematopoietic stem cell transplantation (aHSCT) is increasingly used to treat patients with highly active multiple sclerosis (MS) refractory to disease-modifying therapy. Briefly, cyclophosphamide and filgrastim are used to mobilize autologous hematopoietic stem cells (HSC) into the circulation. HSC are harvested by leukapheresis, purified using a CD34 immunomagnetic selection process, and cryopreserved. Busulphan, cyclophosphamide, and rabbit anti-thymocyte globulin are used to destroy the patient's autoreactive immune system, followed by infusion of the previously collected HSC, which reconstitute a naïve and self-tolerant immune system. Many MS patients experience durable remissions with no evidence of new disease activity following aHSCT. Treatment-related toxicity is rare, but potentially life-threatening complications necessitate appropriate patient selection by MS neurologists and HSCT physicians. AHSCT must be performed with a highly trained multidisciplinary team expert to minimize morbidity and mortality. We present the current aHSCT procedure for an MS indication at The Ottawa Hospital, developed from our program's 20-year experience. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Candidate selection Basic Protocol 2: Autologous hematopoietic stem cell mobilization, collection, purification, and cryopreservation Basic Protocol 3: Autologous hematopoietic stem cell transplantation Basic Protocol 4: Supportive care following recovery from aHSCT (Beyond 100 days) Basic Protocol 5: Ongoing evaluation of multiple sclerosis.

314 - Plerixafor Combined with G-CSF for Pediatric Autologous Hematopoietic Stem Cell Mobilization

314 - Plerixafor Combined with G-CSF for Pediatric Autologous Hematopoietic Stem Cell Mobilization

Plerixafor use in autologous hematopoietic stem cell mobilization: Experience from a single center in Southern India.

BACKGROUND:Plerixafor is used for patients at risk of Stem cell mobilization failure based on clinical factors or low peripheral blood CD34 count. It is also added upfront to any mobilization irrespective of risk factor, but the cost-effectiveness of the approach is an issue. Data on plerixafor in different settings of autologous hematopoietic stem cell (HSC) collection from India are scant. We are hereby reporting the experience of failure/success of mobilization rate and few important significant variables (CD34+ dosage, failed collection) between plerixafor and granulocyte colony-stimulating factor alone groups among autologous hematopoietic stem cell transplantation (aHSCT) at our institute.METHODS:This was a record-based single-center study on patients who underwent aHSCT from January 2013 to June 2019 at a tertiary care hospital. Descriptive statistics were used for baseline characteristics, transplant-related factors, and peritransplant outcomes. All statistical analyses were performed at the 5% significance level.RESULTS:During the study duration, a total of 96 patients had undergone autologous hematopoietic stem cell collection (aHSCC), all by peripheral blood stem cell harvest, requiring 131 apheretic collections. Of the total 131 collections in 96 patients, plerixafor was used in 63 apheresis collections (48% of total pheresis) in 40 patients. Among the 40 patients who were administered plerixafor to augment the collection, 34 patients had upfront use of plerixafor. We did not observe any significant adverse event related to plerixafor use.CONCLUSION:A rational utilization of plerixafor can facilitate the process and logistics of aHSCC outcome.

Analysis of Factors Influencing Autologous Peripheral Blood Stem Cells Mobilization in Patients with Lymphoma and Multiple Myeloma

To analyze the factors influencing the mobilization of autologous peripheral blood stem cells (auto-PBSCs) in patients with lymphoma and multiple myeloma, and provide reference for optimizing the autologous stem cell mobilization regimen. Clinical data of 33 multiple myeloma and lymphoma patients received auto-PBSCs mobilization in our center from January 2015 to December 2018 were collected, the correlation of mobilization failure rate with gender, age, courses of chemotherapy before mobilization, does of recombinant human granulocyte colony stimulating factor (rhG-CSF), type of disease, and chemotherapy regimen were retrospectively analyzed. Type of disease and course of pre-mobilization chemotherapy could affect the mobilization failure rate (P<0.05). The mobilization failure rate of lymphoma patients was 42.1%, which was significantly higher than 7.1% of multiple myeloma patients (P=0.026). The mobilization failure rate was higher in the group with chemotherapy courses≥5 before mobilization (P=0.016). Age, gender, dose of rhG-CSF, and chemotherapy regimen had no significant correlation with mobilization failure rate (P>0.05). Multi-course chemotherapy before collection and lymphoma patients are poor factors negatively impacting on auto-PBSCs mobilization.

Mobilization of backup autologous peripheral stem cells in pediatric thalassemia patients: A single center experience

Mobilization of backup autologous peripheral stem cells in pediatric thalassemia patients: A single center experience

Effectiveness and Safety of Autologous Stem Cell Mobilization with Granulocyte Colony Stimulating Factor in an Inpatient or Outpatient Setting

Effectiveness and Safety of Autologous Stem Cell Mobilization with Granulocyte Colony Stimulating Factor in an Inpatient or Outpatient Setting

Initial Safety Results from a Phase II Study of Acalabrutinib Plus RICE Followed By Autologous Hematopoietic Cell Transplantation and/or Acalabrutinib Maintenance Therapy for Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Background: Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) often have a poor prognosis despite therapies using second-line chemoimmunotherapy (CIT). Achievement of complete response (CR) with second-line therapy is associated with improved long-term outcomes. Unfortunately, only 25-35% of patients achieve CR with standard CIT regimens alone. The addition of novel targeted agents such as Bruton Tyrosine Kinase inhibitors (BTKi) to second-line therapy may offer improved treatment responses given the importance of B-cell receptor (BCR) signaling in DLBCL. BTK has been shown to be essential for BCR-mediated activation of the NF- κB/Rel family of transcription factors and BCR signaling has been recognized as a key pathway in the pathogenesis of DLBCL. Moreover, NF-κB activity relies upon chronic active BCR signaling in activated B-cell-like DLBCL, which can be potentially blocked by kinase inhibitors targeting BTK. In this study we examine the feasibility and efficacy of adding the BTKi, acalabrutinib (A), to standard second-line therapy to improve disease response in patients with R/R DLBCL. Here we present initial safety and tolerability data for the ongoing study.Study Design and Methods: This is an open-label, prospective phase II trial (NCT03736616). Cohort A is open to R/R DLBCL patients eligible for autologous hematopoietic transplantation (HCT). Cohort B is open to R/R DLBCL patients considered ineligible for autologous HCT. The primary endpoint for cohort A is to estimate the confirmed CR rate (RECIL 2017 criteria) prior to autologous HCT in patients undergoing second-line CIT. The primary endpoint for cohort B is defined as the estimate of one-year progression-free survival in patients undergoing second-line induction and maintenance acalabrutinib therapy.Cohort A receive 2 cycles of standard RICE salvage CIT in combination with acalabrutinib, 100mg BID days 1-21 of a 21-day cycle (RICE+A). After 2 cycles of therapy, patients undergo autologous stem cell mobilization and collection. Patients then receive a 3 rd cycle of RICE in combination with acalabrutinib. PET-CT (PET3) is to be performed on day 15 of cycle 3 to assess response. Patients with CR or partial response (PR) after PET3 proceed to autologous HCT with BEAM conditioning within 28-42 days of PET3. Post-HCT CR patients receive acalabrutinib 100mg BID as maintenance therapy for 12 additional months. Protocol amendment in May 2021 allows for PET assessment (C2D15) prior to autologous stem cell collection (after cycle 3).Cohort B receive 3 cycles of RICE+A in 21-day cycles followed by PET-CT (PET3) on day 15 of cycle 3. Patients without progressive disease at PET3 continue with acalabrutinib maintenance up to 12 additional cycles until disease progression or unacceptable toxicity. Patients demonstrating progressive disease are withdrawn from study treatment but followed for outcomes.Results: Here we report initial safety and tolerability data for the ongoing study with data cutoff July 28, 2021. Twenty-two patients have been screened and 20 patients have received at least 1 cycle of RICE+A. Patient characteristics are shown in Table 1. Fifteen patients (79%) have completed 3 cycles of RICE+A. One patient (5%) discontinued due to an adverse event (AE; recurrent appendicitis), 3 patients (16%) discontinued due to progressive disease, and 1 patient is receiving ongoing RICE+A as of data cutoff. Hematologic AE have been observed in 17 patients (89%) with 74% being Grade 3/4. Amongst these, neutropenia was the most common AE occurring in 47% with all being Grade 3/4, and thrombocytopenia occurring in 32% with all being Grade 3/4. All hematologic AE recovered to baseline or grade 1 in median 7 days. Amongst non-hematologic AE, diarrhea occurred in 21% and 0% were Grade 3/4, nausea 16% with 0% Grade 3/4, and headache in 16% with 0% Grade 3/4. Discontinuation of therapy due to AE occurred in 1 patient (recurrent appendicitis) and dose reduction occurred in 1 patient (Gr 4 neutropenia). Temporary (per protocol) dose holds of A occurred in 9 patients (45%), primarily for cytopenias during concurrent RICE+A. Median duration for dose holds of A was 5.5 days.Conclusion: RICE+A is feasible with manageable primarily hematologic AEs similar to those reported for RICE alone. Enrollment and follow up is ongoing for efficacy endpoints and further toxicity assessment. [Display omitted] DisclosuresBensinger: BMS, Janssen, Poseida, Regeneron, Trillium: Research Funding; Amgen, BMS, Janssen, Sanofi: Speakers Bureau. Glennie: Pharmacyclics/Janssen: Speakers Bureau. Pagel: Pharmacyclics/AbbVie: Consultancy; Incyte/MorphoSys: Consultancy; MEI Pharma: Consultancy; Gilead: Consultancy; Actinium Pharmaceuticals: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy; Kite, a Gilead Company: Consultancy; Epizyme: Consultancy. Patel: Bristol Myers Squibb: Consultancy, Speakers Bureau; Janssen: Consultancy; Genentech: Consultancy; BeiGene: Consultancy; TG Therapeutics: Consultancy, Speakers Bureau; Abbvie: Consultancy; Pharmacyclics: Consultancy; Morphosys: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; MEI Pharma: Consultancy; ADC Therapeutics: Consultancy; Lilly: Consultancy. OffLabel Disclosure:Acalabrutinib is not FDA approved for treatment of DLBCL and is discussed in the context of an ongoing clinical trial only.

Meloxicam with Filgrastim may Reduce Oxidative Stress in Hematopoietic Progenitor Cells during Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Multiple Myeloma.

Autologous stem cell transplantation (ASCT) is a potentially curative therapy but requires collection of sufficient blood stem cells (PBSC). Up to 40 % of patients with multiple myeloma (MM) fail to collect an optimum number of PBSC using filgrastim only and often require costly plerixafor rescue. The nonsteroidal anti-inflammatory drug meloxicam mobilizes PBSC in mice, nonhuman primates and normal volunteers, and has the potential to attenuate mobilization-induced oxidative stress on stem cells. In a single-center study, we evaluated whether a meloxicam regimen prior to filgrastim increases collection and/or homeostasis of CD34+ cells in MM patients undergoing ASCT. Mobilization was not significantly different with meloxicam in this study; a median of 2.4 × 106 CD34+ cells/kg were collected in the first apheresis and 9.2 × 106 CD34+ cells/kg were collected overall for patients mobilized with meloxicam-filgrastim, versus 4.1 × 106 in first apheresis and 7.2 × 106/kg overall for patients mobilized with filgrastim alone. CXCR4 expression was reducedon CD34+ cells and a higher CD4+/CD8+ T-cell ratio was observedafter mobilization with meloxicam-filgrastim. All patients treated with meloxicam-filgrastim underwent ASCT, with neutrophil and platelet engraftment similar to filgrastim alone. RNA sequencing of purified CD34+ cells from 22 MM patients mobilized with meloxicam-filgrastim and 10 patients mobilized with filgrastim only identified > 4,800 differentially expressed genes (FDR < 0.05). Enrichment analysis indicated significant attenuation of oxidative phosphorylation and translational activity, possibly mediated by SIRT1, suggesting meloxicam may counteract oxidative stress during PBSC collection. Our results indicate that meloxicam was a safe, low-cost supplement to filgrastim mobilization, which appeared to mitigate HSPC oxidative stress, and may represent a simple means to lessen stem cell exhaustion and enhance graft quality.

Factors affecting the mobilization and collection of autologous peripheral blood hematopoietic stem cells

Factors affecting the mobilization and collection of autologous peripheral blood hematopoietic stem cells

A Phase 1/2 Study of Carfilzomib Combined with Rituximab, Ifosfamide, Carboplatin and Etoposide (C-RICE) in Patients with Transplant-Eligible, Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

Background: The CORAL study highlighted the need to develop novel salvage regimens in R/R DLBCL previously treated with R+CHOP. Overall response rate (ORR) to second line chemotherapy (either RICE or RDHAP) was 51% in patients previously treated with R-CHOP with a 3-year progression free survival (PFS) of only 30%. In the SCHOLAR-1 study, pts with chemo-refractory disease had a worse prognosis with ORR of approximately 26% and a median overall survival (OS) of 6-7 months. We previously demonstrated that 1) the ubiquitin-proteasome system (UPS) plays an important role in acquired rituximab-chemotherapy resistance in DLBCL and 2) that carfilzomib (CFZ), a selective, irreversible proteasome inhibitor, overcomes rituximab-chemotherapy in lymphoma pre-clinical models. We hypothesize that targeting the UPS with CFZ could result in higher response rates and improved outcomes following high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) in R/R DLBCL pts.Methods: We are conducting a single-center, open-label, prospective Phase I/II clinical trial evaluating the safety, efficacy, and pharmacokinetics/pharmacodynamics (PK/PD) of CFZ in combination with R-ICE in HDC-ASCT eligible R/R DLBCL (NCT01959698). Here, we present the results of the Phase I part of the study. Classic 3+3 dose escalation of CFZ was utilized for the phase 1 portion. Primary objectives were to determine the maximum tolerated dose (MTD) and examine the dose-limiting toxicities (DLT) of CFZ in combination with R-ICE. Secondary objectives include feasibility of successful mobilization of autologous stem cells, preliminary evaluation of activity and PK/PD analysis. Patients received CFZ on days 1, 2, 8, 9, rituximab on day 3 followed by ICE (days 4-6) at standard doses. Cycles were repeated every 21 days for a maximum of 3 cycles before HDC-ASCT. Toxicity was assessed using NCI CTCAE version 4; responses were assessed after 2 and 3 cycles using revised Cheson criteria.Results: As of July 20th, 2017, a total of 14 pts have been enrolled in the phase 1 portion at 10 mg/m2 (n=3) (dose level 1 [DL1]), 15 mg/m2 (n=3) (DL2), 20 mg/m2 (n=3)(DL3), 20 mg/m2 d1-2, 27 mg/m2 d8-9 (n=3)(DL4), and 20 mg/m2 d1-2, 36 mg/m2 d8-9 (n=2)(DL5). Median age 60 yrs, 64% males, median time from diagnosis 14.8 (4.1-77.3) mo, 6/14 (43%) were primary refractory, 5/14 pts have a germinal center B-cell like (GCB) subtype, 8/14 pts have a non-germinal center (non-GBC subtype) by Han's criteria, 1 pt has T cell/histiocyte rich large cell lymphoma. Two pts have double hit (DL) DLBCL by FISH studies and 2 have a sole MYC rearrangement. With one more dose-level to test (DL6), no DLTs have been recorded so far. The MTD is yet to be defined. Majority of the grade 3/4 drug-related adverse events (AEs) reported were hematological (thrombocytopenia- 71%, anemia- 50%, neutropenia- 43%, lymphopenia 7%, febrile neutropenia 14.3%). Grade 3 non-hematological AEs include gastrointestinal hemorrhage (1), device-related infection (1), abscess at biopsy site (1), dehydration (1), hyperglycemia (1), hypokalemia (1), hypophosphatemia (1), headache (1), dyspnea (1), pulmonary embolism (1). Grade 4 non-hematological AEs were hypocalcemia (1) and hypokalemia (1). Preliminary results demonstrate an ORR of 64% (50% CR, 14% PR) (Figure 1). Interestingly, an ORR of 100% was observed in pts with relapsed non-GCB DLBCL subtype (all CRs). In contrast, all patients with primary refractory DLBCL fared poorly (1- partial response, 3-stable disease, 2- progressive disease) and were unable to proceed to HDC-ASCT. All responding patients (N=8) underwent successful stem cell collection and received HDC-ASCT. The median TTP post HDC-ASCT, PFS and OS have not been reached. PK/PD/correlative data will be presented at the meeting.Conclusion: C-RICE is well tolerated in pts with R/R DLBCL with toxicities comparable to RICE chemo-immunotherapy. The selective higher CR rate (100%) observed in non-GCB DLBCL highlights the effects of CFZ in NFκB activity and its contribution to chemotherapy resistance. Our data suggest that non-GCB DLBCL benefit significantly from incorporating CFZ into second line therapy and HDC-ASCT. The phase II of the study will commence shortly and tailoring enrollment to non-GCB R/R DLBCL may optimize treatment options to all subtypes of R/R DLBCL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Low-Dose Plerixafor and Granulocyte Colony-Stimulating Factor for First-Line Autologous Peripheral Blood Stem Cell Mobilization in Lymphoma and Multiple Myeloma

Introduction: Approximately 10-30% of candidates to autologous hematopietic stem cell transplant (HSCT) are unable to collect an adequate yield of CD34+ cells/kg to support high-dose chemotherapy and autologous HSCT. Peripheral blood stem cell (PBSC) mobilization strategies vary considerably but the optimal methodology for mobilizing PBSC is not well defined. Plerixafor (Mozobil®) is approved for the mobilization of PBPC in combination with G-CSF at a dose of 0.24 mg/kg once daily for up to 4 consecutive days; however, it is an expensive drug and is expected to increase costs associated with PBSC harvest. Failure of peripheral blood (PB) mobilization and harvest is a critical issue for multiple myeloma (MM) and non hodgkin´s lymphoma (NHL) since the correlation between successful engraftment and the number of CD34+ cells infused is well established. We aim to investigate the safety and efficacy of the administration of low-dose plerixafor in mobilizing CD34+ cells plus G-CSF in MM and NHL.Methods: It is a preliminary report of a single-institution, open-label, phase II trial to test the feasibility and efficacy for mobilization of low-dose plerixafor added to daily G-CSF administration in adult patients with MM or NHL undergoing autologous HSCT. Institution ethic board approved the trial and all patients provided written informed consent. Consecutive patients in autologous transplant protocol with MM or NHL were included. The mobilization protocol consisted of G-CSF (10 μg/kg) subcutaneously daily for 4 days and plerixafor (0.12 mg/kg) administered subcutaneously 11 hours prior to initiation of apheresis. Stem cells collection was performed with a Cobe Spectra® or Spectra Optia® apheresis system. The planned target blood volume to be processed was 4-fold total blood volume calculated according to patients' weight and size. Peripheral blood CD34+ counts were analyzed using flow cytometry. Primary endpoint was the proportion of patients achieving at least 2 x 106 CD34+cells/kg in 1 apheresis harvest. Secondary end points included the rate of successful CD34+ cell mobilization, defined as a peak of CD34+ cells in PB >20 cells/mL. We measure PB CD34+ cells the day 4 and 5 after plerixafor administration. Toxicities and engraftment were documented.Results: Between april 2017 and july 2017, nine patients has been enrolled. Six with MM and 3 with NHL. The median PB CD34+ cell count for patients on day 4 before receiving plerixafor was 12.3/mL (range, 2.2-168.8) and 65.4/mL (range, 8.2-360.7) on day 5 after plerixafor (P=0.103). The median collection yield was 4.9 x 106 CD34+ cells/Kg (range, 1.4 - 24.5 million CD34+ cells/Kg). Plerixafor was well tolerated in most patients, only 2 referred moderate diarrhea. Eight of the 9 patients reached the target cell count (88.8%) with only 1 day of collection. Seven of nine patients had hematopoietic recovery with median neutrophil and platelet engraftment of 14 (range, 10-16) and 12 days (range, 10-16), respectively. Two patients are on day +1 and +5 and waiting for engraftment.Conclusions: Failure of PBSC mobilization is a critical issue for MM and NHL patients undergoing autologous HSCT. The combination of low-dose plerixafor with G- CSF in this study achieved 88% of successful yields, and appears to be an efficient and safe approach in first-line to improve the success of the yield. Aside of the costs related to plerixafor, this strategy can be counterweighed by reducing other resources as reducing number of apheresis and possibly reducing the impact on quality of life for patients. DisclosuresGomez-Almaguer:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Real World Clinical Experience of Biosimilar G-CSF (Grastofil) for Autologous Peripheral Blood Stem Cell Mobilization: Single Center Experience in Canada Following Early Adoption.

Introduction: Granulocyte colony-stimulating factor (G-CSF) is the first line treatment for mobilization, most commonly using a regimen of daily filgrastim. The use of biosimilars can provide substantial cost savings to the health care system while delivering comparable efficacy outcomes. In 2016, the Saskatchewan Cancer Agency was a leader in Canada, instituting formulary changed from a G-CSF originator product to a cost savings alternative biosimilar for stem cell mobilization prior to autologous stem cell transplant (ASCT) and for engraftment. The purpose of this study was to investigate the clinical comparability of biosimilar G-CSF to its reference product in a real-world clinical setting and to validate use of the biosimilar in mobilization and engraftment—an indication which had been granted by extrapolation. Methods: A retrospective chart review was completed including all patients diagnosed with a hematological malignancy between 2012 and 2018 who underwent ASCT. To assess real-world outcomes across a diverse population, successful CD34+ stem cell collection was compared between patients mobilized with originator filgrastim, Neupogen, and biosimilar filgrastim, Grastofil. Additional comparisons included the number of apheresis required, time to absolute neutrophil count (ANC) engraftment, platelet engraftment, length of hospital stay, and Plerixafor use. Results: 217 patients were mobilized and transplanted during the study period. There was no statistically significant difference in success rate between patients mobilized with biosimilar filgrastim and those who had received originator G-CSF (100% vs. 92.4%, p = 0.075). Neither disease type, nor concurrent chemomobilization regimen resulted in a detectable difference between the two G-CSF products in successful stem cell harvest. Engraftment was highly similar between groups, as demonstrated by ANC recovery (11.6 days Neupogen vs. 11.6 days Grastofil), platelet recovery (14.0 days Neupogen vs. 14.2 days Grastofil), and total length of hospital stay (22.4 days Neupogen vs. 22.3 days Grastofil). No statistically significant difference in adjunctive use of Plerixafor® was observed between Neupogen and Grastofil patients (25.9% vs. 23.4%, p = 0.72). Conclusion: Extrapolation of indications for biosimilars is justified. This real-world evidence builds upon registrational studies to confirm that no clinically meaningful differences were detected between originator Neupogen and biosimilar Grastofil in the setting of PBSC mobilization and engraftment post ASCT. Biosimilars are as safe and effective as originator products. Implementation across all approved indications without hesitation maximizes cost savings to the provincial system, allowing for more optimal allocation of health care resources.

Prolonged Lenalidomide Therapy Does Not Impact Autologous Peripheral Blood Stem Cell Mobilization and Collection in Multiple Myeloma Patients: A Single-Center Retrospective Analysis

Since the introduction of lenalidomide into induction therapy for multiple myeloma (MM), there have been conflicting reports about its impact on autologous peripheral blood stem cell (PBSC) mobilization. We evaluated the impact of previous lenalidomide exposure in a large cohort of patients with MM undergoing mobilization and collection at a tertiary stem cell transplantation center. We hypothesized that collection of PBSCs is feasible even with a prolonged duration of previous lenalidomide therapy. We examined patients with MM who attempted stem cell mobilization and collection, seen at our center between January 2012 and July 2015. The patients were categorized into 3 groups for analysis: (1) patients with previous receipt of >6 cycles lenalidomide, (2) patients with previous receipt of ≤6 cycles of lenalidomide, and (3) patients without previous lenalidomide exposure. We compared collection yields and days of apheresis among the 3 groups using linear regression analysis. We identified 297 patients with MM who underwent mobilization of PBSCs. Of these, 35 had received >6 cycles of lenalidomide (median, 8 cycles; range, 7 to 25 cycles), 156 had received ≤6 cycles of lenalidomide (median, 4 cycles; range, 1 to 6 cycles), and 106 had received no lenalidomide. Prior lenalidomide exposure did not have a statistically significant impact on the absolute number of CD34+ cells collected or on the duration of collection based on a multivariate linear regression analysis for association between receipt of >6 cycles of lenalidomide. In this retrospective analysis of MM patients undergoing autologous PBSC transplantation, we show that the duration of previous lenalidomide exposure does not impact the total number of PBSCs collected or the number of days of apheresis. These data suggest that longer courses of induction therapy with lenalidomide-containing regimens to achieve a maximum response can be safe without impairing the ability to collect PBSCs, and that limiting lenalidomide use before mobilization does not appear warranted in all cases.

Effect on Patients’ Outcomes of a Change to Biosimilar Filgrastim Product in Autologous Stem Cell Mobilization

Following addition of a biosimilar filgrastim product to the formulary, sites in the authors' provincial health authority transitioned from using the originator filgrastim to the biosimilar for autologous stem cell mobilization. To assess the effect on patient outcomes of a universal change to use of the biosimilar filgrastim in stem cell mobilization. This retrospective pre-post study included patients undergoing autologous stem cell mobilization at 2 cancer hospitals in Alberta, Canada, between July 1, 2018, and November 30, 2019. Clinical outcomes were investigated for patients treated with a granulocyte colony-stimulating factor (biosimilar or originator product) for mobilization before stem cell transplant, approximately 6 months before and after the defined date of product change. In total, 102 patients were treated with the originator product and 101 patients with the biosimilar. Effectiveness was similar between the originator and biosimilar products, with 98% successful harvest of stem cells in all patients treated. Independent t tests showed no statistically significant differences between patients receiving the originator and those receiving the biosimilar in terms of time from mobilization to collection (difference of means -0.9 days, 95% confidence interval [CI] -2.12 to 0.32), time for neutrophil engraftment (difference of means 0 days, 95% CI -0.36 to 0.36), time for platelet engraftment (difference of means 1 day, 95% CI -0.55 to 2.55), average length of stay (difference of means -0.7 day, 95% CI -2.71 to 1.31), and CD34+ value (difference of means -1 × 106/kg body weight, 95% CI -2.11 to 0.11). A 98% rate of conversion to use of the biosimilar filgrastim was achieved, with an estimated annual drug-cost saving of $67 500. In this pre-post study, changing to the biosimilar product from the originator maintained clinical effectiveness outcomes while decreasing overall drug expenditures. A well-planned change to the biosimilar product, executed in conjunction with clinician consultation and monitoring of effectiveness outcomes, can ensure appropriate patient therapy while significantly improving the uptake of biosimilars and decreasing expenditures for biologic drugs.

CXCR4 ANTAGONIST AMD3100 PROMOTES MILD IMPROVEMENTS OF CARDIAC FUNCTION AND PULMONARY MECHANICS IN PULMONARY HYPERTENSIVE RATS

Background Pulmonary arterial hypertension (PAH) is a lethal cardiopulmonary disease characterized by an increase in resting pulmonary pressure ≥25 mmHg. Poor survival and functional limitations of PAH patients have fueled research for new alternative therapeutic strategies. So far, pre-clinical findings suggested promising effects of stem cell-based therapies. AMD3100 is a highly selective CXCR4 antagonist that enhances autologous bone marrow-derived stem cell mobilization and is currently used in stem cell transplantation and the treatment of leukemia. So far, however, it remains unclear whether AMD3100 can provide salutary effects in the treatment of PAH. Methods PAH was induced in adult male Wistar rats (Protocol number 087/15) by an intraperitoneal injection of monocrotaline (MCT, 60 mg/kg IP), while the Control (CTL) group was treated an equivalent volume of vehicle. Two weeks after the MCT injection, MCT-administered rats were randomly treated with AMD3100 (1 mg/kg/day IP for 14 days) or vehicle, totalling 3 groups: CTL, MCT, and AMD3100. Echocardiography and pneumotachography were used to assess cardiac function and pulmonary mechanics, respectively. Right ventricular (RV) hypertrophy was assessed by the Fulton index. Data were analyzed with One-way and Two-way ANOVA (Prism®, GraphPad) and were expressed as mean ± SEM. Results MCT and AMD3100 groups exhibited an equally progressive decrease in body weight compared to the CTL group (p Conclusion Our study indicates that treatment with AMD3100 provides mild improvement of cardiac and pulmonary function in pulmonary hypertensive rats.