Peripheral blood stem cell collection for patients with multiple myeloma undergoing autologous transplant after quadruplet induction Free

Background: In recent years, quadruplet induction regimens, including daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRD) and daratumumab, carfilzomib, lenalidomide and dexamethasone (D-KRD) are increasingly used for patients with newly diagnosed multiple myeloma (MM). There are limited data on the impact of these anti-CD38 containing regimens on the collection of CD34 peripheral blood stem cells (PBSC) in transplant-eligible MM patients.

Methods: We performed a retrospective, single-center analysis on newly diagnosed MM patients, who received D-VRD or D-KRD quadruplet induction followed by autologous stem cell transplantation (autoHCT) between January 2021 and August 2024. We divided patients into two groups: low (<5 X10⁶/Kg) or high (≥5 X10⁶/Kg) collected CD34+ cells. High risk cytogenetic abnormalities (HRCA) were defined as del17p, t(4;14), t(14;16), 1q21 gain or amplification by fluorescence in situ hybridization. Primary outcomes analyzed were time to neutrophil and platelet engraftment, progression-free survival (PFS), and overall survival (OS). Minimal residual disease (MRD) status was determined in bone marrow samples using an 8-color next generation flow (NGF) assay with a sensitivity of 1/10⁵ cells (0.001%) on 2 million events.

Results: Out of 140 patients included in our analysis, 125 (89%) received D-VRD induction and 15 (11%) received D-KRD. There were 22 (16%) patients in the low CD34 group and 118 (84%) in the high CD34 group. In the entire cohort, patients received a median of 4 induction cycles (range 2-11). There was no significant difference between the low or high CD34 groups in proportion of patients who received ≥4 induction cycles (95% vs. 89%; p=0.70). Compared to the high CD34 group, patients in the low CD34 group were older (median age 68.5 years vs. 60 years; p<0.001), required more days of stem cell collection (median of 4 days vs. 3 days; p=0.003), and more often required >3 days of collection (82% vs. 45%; p=0.002). The majority of patients in both CD34 groups (n=123, 88%) received GCSF+plerixafor for stem cell mobilization. Six patients received chemo-mobilization with cyclophosphamide, all in the high CD34 group.

Male patients collected a significantly higher number of PBSC compared to females (median 6.8 vs. 6.2 CD34 X10⁶/Kg cells; p=0.031). However, race (black or non-black; p=0.44), cytogenetic risk (standard or high; p=0.68), type of induction regimen (D-VRD or D-KRD; p=0.81), number of induction cycles (<4 or ≥4; p=0.74), duration of induction (<4 months or ≥4 months; p=0.75), maximal lenalidomide dose during induction (<20mg or ≥20mg; p=0.25) or hematological response prior to transplant (p=0.18) did not have a significant impact on the number of PBSC collected.

Time to platelet (Plt) engraftment (Plt>20K) was 12 days in both CD34 groups, and time to neutrophil engraftment (ANC>500) was 13.5 and 13 days in the low and high CD34 groups, respectively. Median duration of hospitalization for autoHCT was 17 days in both groups.

There was no significant difference between the CD34 groups in pre-transplant (p=0.10), day-100 (p=0.46) or best post-transplant (p=0.39) hematological responses. Similarly, there was no difference in rates of MRD-negative status pre-transplant (p=0.49) or at best post-transplant response (p=0.44) between the two groups.

After a median follow up of 18.7 (3.6-47.4) months, there was no significant difference in PFS or OS between the two CD34 groups. The 2-year PFS rates were 87% and 88% in the low and high CD34 groups, respectively (p=0.74). The 2-year OS rates were 89% and 94% in the low and high CD34 groups, respectively (p=0.62). There was also no significant difference in 2-year rates of PFS (100% vs. 87%; p=0.40) or OS (100% vs. 93%; p=0.71) between patients who received <2.5 or ≥2.5 X 10⁶/Kg cells infused at autoHCT.

Conclusion: In our cohort, approximately one in six patients who received quadruplet induction had suboptimal PBSC collection prior to autoHCT, which was more commonly seen in older patients. The number of induction cycles and lenalidomide dose during induction did not significantly impact the yield of stem cell collection. A lower CD34 collection did not adversely impact the engraftment, response rates or survival outcomes.