Impact of Daratumumab-Containing Induction Therapy on Stem Cell Mobilization in Multiple Myeloma: A Retrospective, Single-Center Analysis
Authors: Figueiroa Hegta R. , Medeiros Germano , Pessoa Juliana Matos , Zenero Paula Lucafo , Pittol Isabella , Ayoub Fauze Lutfe , Machado Pedro Paulo Faust , Camargo Gabriela , Delijaicov Dimitra Oliveira , Larubia André , Lazar Arlett Edna , Filho Jose Ulysses A. , Gusmao Breno , Kerbauy Fabio R. , Americo André Dias , Scheinberg Phillip 
Published: December 2024

Introduction:
Autologous hematopoietic stem cell transplantation (aHSCT) remains a cornerstone treatment for multiple myeloma (MM). A significant limitation in peripheral blood stem cell (PBSC) collection is the challenge of obtaining a sufficient quantity of hematopoietic progenitor stem cells (hSC) in some cases. This study aimed to assess the impact of daratumumab-containing induction therapy on hSC harvest.
Methods:
We conducted a retrospective, single-center, observational cohort study of all aHSCTs for MM performed from September 2016 to December 2022 at Beneficência Portuguesa de São Paulo (BP). Our center employs a ‘just-in-time’ approach, using a colony-stimulating factor followed by plerixafor as the preferred mobilization regimen. We analyzed the impact of pre-mobilization daratumumab exposure on stem cell yield, mobilization failure, and plerixafor requirement. Multivariate logistic regression was used to evaluate predictors of plerixafor use, and multivariate linear regression was applied to assess predictors of hSC yield.
Results:
A total of 333 mobilizations for aHSCT were performed, with data available for 306 mobilizations. The median patient age was 63 years. The mobilization strategies included filgrastim (n=156) and pegfilgrastim (n=150). Among these patients, 63 received daratumumab-containing protocols, 58 received lenalidomide-containing protocols, and 8 received both agents prior to aHSCT referral. The median number of CD34+ cells collected per million/kg was similar regardless of daratumumab exposure (5.6 vs. 5.54, p &gt; 0.9). However, patients with prior daratumumab exposure experienced higher stem cell mobilization failure rates (0/243, 0% vs. 2/63, 3.2%, p = 0.04) and required plerixafor rescue more frequently (35% vs. 56%, p = 0.002). In the multivariate logistic regression analysis, independent predictors of plerixafor use included lenalidomide exposure (exp(β) 1.90, 95% CI 1.01-3.55, p = 0.04) and pegfilgrastim as the mobilization strategy compared to filgrastim (pegfilgrastim, exp(β) 4.11, 95% CI 2.37-7.07, p &lt; 0.001). The multivariate linear regression analysis identified increased age as independently associated with lower hSC yield (exp(β) 0.91, 95% CI 0.88-0.94, p &lt; 0.001).
Conclusion:
Patients exposed to daratumumab prior to HSCT referral had a higher demand for plerixafor to achieve adequate hSC yield in our cohort. However, this finding was not confirmed in the multivariate linear regression analysis, where only increased age was associated with reduced hSC yield. The predictors of plerixafor utilization due to poor mobilization were lenalidomide use (2-fold increase in risk) and the mobilization strategy involving pegfilgrastim (4-fold increase in risk). We did not pursue a logistic regression analysis for mobilization failure due to the low number of events observed (n=2). Despite the limitations in our study, we conclude that in our cohort, daratumumab-containing induction therapy did not significantly impact stem cell mobilization in patients with MM. However, these findings require further validation by prospective, randomized larger studies.