(PA-446) DVRD Induction Followed by Autologous Hematopoietic Stem Cell Transplantation for Older Patients with Multiple Myeloma

There are limited data on the outcome of older patients with newly-diagnosed multiple myeloma (MM) receiving daratumumab, bortezomib, lenalidomide (Len), and dexamethasone (DVRD) followed by upfront autologous transplant (autoHCT). In both the GRIFFIN (Voorhees et al. Blood 2020) and PERSEUS (Sonneveld et al. NEJM 2024) trials the upper age limit for inclusion was 70 years.

Methods:

This is a single-center, retrospective chart review of consecutive adult MM patients that received upfront autoHCT after standard of care DVRD between 2021-2024. Primary outcomes were progression-free (PFS) and overall survival. We used stabilized inverse probability weights (IPW) to compare outcomes between the older group (age ≥70) and the younger group (age < 70).

Results:

125 patients were included: 27 (22%) in the older group and 98 (78%) in the younger age group. Median age at autoHCT was 74 (range 70-78) years for the older group and 59 (40-69) years for the younger group. 16 (64%) patients in the older group had R2-ISS III/IV and 12 (44%) had high-risk cytogenetic abnormalities, compared to 42 (49%; p=0.26) and 52 (53%; p=0.52) in the younger group, respectively. Most patients received post-transplant maintenance (85% in the older group and 82% in the younger group; p=0.78), mostly Len alone (65% and 71%, respectively).

Median time to neutrophil engraftment (ANC >500) after transplant was 12 days (range 10-15) in the older group and 12 days (range 10-13) in the younger age group (p=0.06), and median time to platelet engraftment (plt >20K) was 14 days (range 10-18) and 13 days (range 9-20), respectively (p=0.09).

The pre-and post-transplant response rates in the older and younger groups were ≥CR and ≥VGPR: pre-transplant 30% and 81% vs. 24% (p=0.62) and 78% (p=0.79); at best post-transplant response 78% and 100% vs. 77% and 99% (both p=1.00), respectively. Prior to transplant, 42% of the patients in the older group achieved MRD negativity compared to 49% in the younger group (p=0.66); at best-post transplant response, 50% and 75% had MRD negativity, respectively (p=0.10).  

After a median follow up of 19.1 (range 3.6-47.4) months, 1-year and 2-year PFS rates were 91% and 78% for the older age group vs. 93% and 89% in the younger group (p=0.41). The median OS was not reached for both age groups. 1-year and 2-year OS rates were 100% and 92% in the older age group vs. 98% and 93% in the younger group. There was no significant difference in either PFS (hazard ratio [95% CI] 1.23 [0.34-4.42], p=0.75) or OS (0.49 [0.02-14.29], p=0.68) between the two age groups, using stabilized inverse probability weights.

There were no non-relapse mortality (NRM) events in both age groups. Four patients developed second primary malignancies, all in the younger age group.

Conclusions:

MM patients aged ≥70 years, who  received DVRD induction followed by autoHCT had similar response rates, PFS and OS  as younger patients, without any treatment-related deaths.