Effect of Prior Daratumumab Treatment on Hematopoietic Progenitor Cell Mobilization in Newly Diagnosed Multiple Myeloma

Background:

Autologous hematopoietic cell transplantation (HCT) is a standard of care consolidation treatment after induction therapy for multiple myeloma (MM). Hematopoietic progenitor cell (HPC) mobilization has been shown to be affected by prior induction therapy. The monoclonal CD38 antibody daratumumab (dara) has been increasingly used as part of frontline treatment or salvage therapy in patients with new MM who are eligible for autologous HCT. It has been previously suggested that patients treated with dara have decreased yield of HPC mobilization as demonstrated by Hulin et al in the CASSIOPEIA study. However, there has been significant variability in these results among institutions. More data are needed to clarify how treatment with dara affects mobilization in these patients. In this study, we analyze mobilization outcomes at our institution for patients who received dara as part of induction therapy compared to those who did not.

Methods:

We retrospectively collected HPC mobilization data on patients undergoing HCT for MM from 1/1/2024 to 7/2/2024 at our institution. All patients were mobilized with G-CSF +/- plerixafor. Plerixafor was administered preemptively or just-in-time for peripheral blood CD34+ count <20/microliter or first day CD34+ yield <2 x10^6/kg. For each patient we determined the day 1 CD34 yield, total CD34 yield, number of apheresis sessions, doses of daratumumab, and mobilizing regimen. Student's t-test or Wilcoxon rank sum test were used to compare numeric variables. Fisher's exact test was used to compare the choice of mobilization regimen. All tests were two-sided and p-values of 0.05 or less were considered statistically significant.

Results:

53 patients with MM underwent HPC mobilization from 1/1/2024 to 7/2/2024. Of these, 37 had previous treatment with dara and 16 did not. The CD34 collection target at our institution is 4 x 10^6 / kg CD34 cells with a minimum of 2 x 10^6 / kg to proceed. Median day 1 CD34 collection was 0.92 x 10^6 / kg (IQR 0.38, 1.6) for patients who received dara and 2.3 x 10^6 / kg (IQR 0.78, 3.8) for those who did not (p = 0.02). Total CD34 collection was 3.5 x 10^6 / kg (SD = 1.9) on average for the dara group and 4.2 x 10^6 / kg (SD = 1.6) for the no dara group (p = 0.22. The dara group required on average 2.5 days (SD = 0.99) of apheresis to complete collection while the no dara group required 1.9 (SD = 0.89) days on average (p = 0.02). There was no significant difference in mobilization regimen. 29.7% (11/37) of the dara group were mobilized with G-CSF + plerixafor while 18.8% (3/16) of the no dara group were mobilized with this regimen (p = 0.51). Patients who received dara received a median of 6 doses (Range = 1, 32).

Conclusion:

We show that patients who received induction therapy with dara collected significantly fewer CD34 cells on day 1 and required significantly more days to complete collection. Our present institutional mobilization algorithm is relatively conservative in regards to upfront plerixafor and does not take prior treatment with dara into account. The results described here argue for strong consideration of upfront plerixafor in patients who have received induction therapy with dara, especially with the recent implementation of generic plerixafor which has reduced cost.

Sauter:GSK: Consultancy; Sanofi-Genzyme: Research Funding; Actinium Pharmaceuticals: Research Funding; Bristol-Myers Squibb: Research Funding; Precision Biosciences: Research Funding; Juno Therapeutics: Research Funding; Cargo Therapeutics: Research Funding; Syncopation Life Sciences: Consultancy; Affimed: Research Funding; NKARTA: Research Funding; CSL Behring: Consultancy; Kite/a Gilead Company: Consultancy; Ipsen Biopharmaceuticals: Consultancy; Gamida Cell: Consultancy; NKARTA: Consultancy; CRISPR Therapeutics: Consultancy; Celgene/BMS: Consultancy; Karyopharm Therapeutics: Consultancy; Ono Pharmaceuticals: Consultancy; MorphoSys: Consultancy; Celgene/BMS: Research Funding. Anwer:BMS: Consultancy. Brunstein:Allovir: Other: Data Safety and Monitoring Board. Raza:Pfizer: Consultancy, Honoraria; Prothena Biosciences: Consultancy; Kite Pharma: Consultancy. Williams:Bristol Myers Squibb: Honoraria; Abbvie Inc.: Research Funding; Janssen: Honoraria. Khouri:Legend: Membership on an entity's Board of Directors or advisory committees; GPCR Therapeutics, Inc.: Honoraria; Prothena: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consultant.