Stem Cell Mobilization Yields with Daratumumab (Dara) and Lenalidomide (Len)-Containing Quadruplet Induction Therapy in Patients with Newly Diagnosed Multiple Myeloma (NDMM): A Real-World Experience at Two Institutes

Background: Quadruplet therapy is quickly becoming standard frontline therapy in transplant eligible NDMM patients. Using data from the MASTER and GRIFFIN trials, Chhabra et al. reported that Dara-Len containing quadruplet therapies had minimal impact on stem cell harvesting and engraftment. It is unclear if this remains true in a real-world setting where heterogeneity exists among patients and in institutional practices. Herein, we describe our experience of stem cell mobilization and collection in NDMM patients receiving DRVd at Levine Cancer Institute (LCI) and Emory Winship Cancer Institute. Methods: In this multi-center retrospective analysis, NDMM patients were eligible if they received DRVd and pursued stem cell collection between 9/2019 and 1/2024 at LCI and 1/2019 and 7/2022 at Emory. Patients either received 10 mcg/kg of growth colony-stimulating factor (G-CSF) daily (LCI) or 7.5mcg/kg twice daily (Emory) for 4 days prior to collection and one dose on the morning of apheresis. Plerixafor was provided on day -1 of apheresis as a preemptive mobilization strategy at LCI and on an as needed basis at Emory. Patients with a suboptimal stem cell yield on day 1 received additional doses of G-CSF with or without rescue plerixafor at both sites followed by a second day of stem cell collection. Stem cell yield failure was defined as the inability to achieve a minimal goal dose of 2.5 × 10⁶ cells/kg. Categorical outcomes were summarized with frequencies and proportions while numerical outcomes were summarized with descriptive statistics. Select data elements were only available in the LCI cohort. Results: A total of 423 patients were analyzed. The median patient age was 62 years (range, 23 - 79 years), and 38.1% of the cohort was African American. Thirteen percent of the cohort had high risk cytogenetics and 19.1% had ISS stage III disease. At LCI, patients received a median of 4 (range, 1 - 14) cycles of induction therapy before stem cell collection. In the entire cohort, 88.8% of patients received 21-day cycles and 11.2% received 28-day cycles. Most patients achieved a VGPR or better (87.2%) after induction and, of those with MRD data available at LCI, 41.6% (37 of 89) achieved MRD negative status (at 10^-5). Of those with available data (n = 92), stem cell collection occurred after a median of 4 weeks (range, 2 to 8) from induction completion. All of the patients at LCI and 308 of the 318 (96.9%) patients at Emory received plerixafor. Among the entire cohort, the median number of total CD34+ cells collected was 9.0 x 10⁶ CD34+ cells/kg (range 0 - 24.1). By institute, the median number of CD34+ cells across all attempts at LCI was 8.5 x 10⁶ CD34+ cells/kg (range 2.9 - 18.1) and the median at Emory was 9.0 x 10⁶ CD34+ cells/kg (0 - 24.1) indicating that there was no significant difference between mobilization strategies (p=0.088). There also was no significant difference in stem cell yield between the 21-day and 28-day cycles; median yield was 9.0 x 10⁶ CD34+ cells/kg vs. 8.6 x 10⁶ CD34+ cells/kg, respectively (p=0.246). 88.2% ( N=373) of patients collected enough for two transplants. Only 2.8% (12 of 423) required an additional mobilization attempt to achieve the minimal target stem cell yield. In the entire population, there was 1 mobilization failure (0.2%) and all but one patient who required remobilization collected sufficient stem cells. Conclusion: The addition of Dara to RVd induction therapy led to impressive hematologic responses and did not have a deleterious effect on stem cell mobilization with an upfront plerixafor strategy. The median stem cell yield in this real-world experience was slightly better than that reported in the GRIFFIN trial.

Varga:LavaTherapeutics: Research Funding; Janssen: Consultancy, Research Funding. Hofmeister:BMS: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Kaufman:Sebia: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Ascentage: Consultancy, Honoraria; Genentech: Consultancy. Dhodapkar:Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Lava Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees. Lonial:AbbVie Inc, Amgen Inc, Bristol Myers Squibb, Celgene Corporation, Genentech, a member of the Roche Group, GSK, Janssen Biotech Inc, Novartis, Pfizer Inc, Regeneron Pharmaceuticals Inc, Takeda Pharmaceuticals USA Inc: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics Inc (no cancer agents currently): Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb, Janssen Biotech Inc, Novartis, Takeda: Research Funding. Ferreri:Janssen: Consultancy; Sanofi: Consultancy; Affimed Therapeutics.: Current equity holder in private company. Paul:Bristol-Myers Squibb: Research Funding; AbbVie Inc: Membership on an entity's Board of Directors or advisory committees; Regeneron Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees. Bhutani:BMS: Research Funding; Takeda: Research Funding; Caribou Biosciences: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Abvvie: Research Funding. Voorhees:Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lava Therapeutics: Consultancy; AstraZeneca: Consultancy; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Joseph:Pfizer Oncology: Research Funding; GSK: Honoraria, Research Funding; BMS: Consultancy, Research Funding; J&J Oncology: Consultancy, Honoraria, Research Funding; AstraZeneca: Research Funding.