(141) Impact of Quadruplet Induction Therapy on Stem Cell Mobilization Yields in Newly Diagnosed Multiple Myeloma

Poster Abstract:

Background:
Standard of care for patients with newly-diagnosed multiple myeloma (NDMM) who are transplant eligible is a three drug induction with bortezomib, lenalidomide, dexamethasone (VRd) followed by autologous stem-cell transplantation (AutoHSCT) and maintenance lenalidomide. Recently, the addition of daratumumab combined with VRd (D-VRd) was shown to improve progression-free survival (PFS) when compared to VRd. However, daratumumab is a known immunosuppressant and may have an impact on hematopoietic stem cell yields, which is critical to successful AutoHSCT. There have been mixed results in demonstrating the impact of daratumumab-containing induction therapy on successful stem cell mobilization and these studies are confounded by inconsistent mobilization practices. To address these inconsistencies, this study utilized upfront plerixafor and granulocyte-colony stimulating factor (G-CSF) for all patients.

Objective:
The purpose of this study is to determine whether the incorporation of quadruple drug induction with daratumumab impairs CD34 cell collection yield compared to standard three-drug induction.

Methods:
This single-center, retrospective observational study included patients 18 years or older with NDMM deemed to be eligible for transplant and who underwent mobilization and collection of CD34 cells at our institution. We included patients that underwent collection from August 2018 to August 2023, and divided them up into two groups. Enrollment was NDMM patients receiving D-VRd or daratumumab-carfilzomib, lenalidomide, dexamethasone (D-KRd) (group1); or, VRd or KRd (group 2). Exclusion criteria included known human immunodeficiency virus (HIV) and first-line treatment other than D-RVd, D-KRd, RVd, or KRd. The primary outcome is the percentage of patients achieving patient-specific minimally required CD34+ cell yield after the first mobilization attempt. Secondary outcomes evaluated the effect of age over 60 years, female sex, the effect of lenalidomide 25 mg, radiation therapy to the spine, greater than or equal to very good partial response (VGPR) status prior to AutoHSCT, and having received over 4 induction cycles. Data will be collected through a manual chart review of the electronic medical record utilizing RedCap. Statistical analysis will include descriptive statistics, chi-squared tests, independent t-tests for normal data, and Wilcoxon rank sum test for non-normally distributed data as appropriate. Multivariable linear regression models will be used to determine factors associated with CD34+ cell yield with covariates based on baseline characteristics such as age, conditioning regimen, and number of stem cell collections required.

Results: Results will be presented at the Hematology/Oncology Pharmacy Association Annual Meeting.

DISCUSSION/

Conclusions: Conclusions will be presented at the Hematology/Oncology Pharmacy Association Annual Meeting.

References (must also be included in final poster): 1. Rosiñol L, Oriol A, Rios R, et al. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma. Blood. 2019;134(16):1337-1345. doi:10.1182/blood.2019000241
2. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. Published online December 12, 2023. doi:10.1056/NEJMoa2312054
3. Krejcik J, Casneuf T, Nijhof IS, et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128(3):384-394. doi:10.1182/blood-2015-12-687749
4. Thurlapati A, Roubal K, Davis JA, et al. Stem Cell Mobilization for Multiple Myeloma Patients Receiving Daratumumab-Based Induction Therapy: A Real- World Experience. Transplant Cell Ther. 2023;29(5):340.e1-340.e4. doi:10.1016/j.jtct.2023.02.013
5. Chhabra S, Callander N, Watts NL, et al. Stem Cell Mobilization Yields with Daratumumab- and Lenalidomide-Containing Quadruplet Induction Therapy in Newly Diagnosed Multiple Myeloma: Findings from the MASTER and GRIFFIN Trials. Transplant Cell Ther. 2023;29(3):174.e1-174.e10. doi:10.1016/j.jtct.2022.11.029