IMS 2025 | Quadruplet induction therapy followed by autoSCT in multiple myeloma: insights from two studies

I will talk about a couple of abstracts that we are presenting at the IMS meeting this year. These are both studies involving myeloma patients who got quadruplet induction followed by autologous transplant and both were performed in collaboration with Dr Kazabash who is a senior author. So the first one is a real-world comparison of DARA-VRD versus DARA-KRD induction in transplant-eligible multiple myeloma. So we know that autologous transplant is still considered standard of care for eligible patients. We have recent evidence from prospective studies that adding an anti-CD38 monoclonal antibody for a quadruplet induction regimen provides deeper responses and longer progression-free survival compared to triplet induction. Specifically, DARA-KRD with carfilzomib and DARA-VRD with Velcade were increasingly used in clinical practice. However, there is limited real-world data comparing these two regimens. We conducted one of the first retrospective analyses directly comparing outcomes of transplant-eligible patients receiving these regimens outside of clinical trial at MD Anderson Cancer Center. We included 140 patients who underwent autologous transplant at our center between 2021 and 2024. After induction with either Dara-VRD, 125 patients, or Dara-KRD, 15 patients. Median age for the entire cohort was 61 years. High-dose melphalan was the most commonly used conditioning regimen used in 67% of patients. Most patients got post-transplant maintenance therapy at 84%. Baseline characteristics were generally balanced, though a maximum lenalidomide dose of 20 milligrams or higher during induction was more commonly used in the DARA-VRD group at 78% compared to 47% in the DARA-KRD group. There was a trend towards a higher proportion of high-risk cytogenetics in the DARA-KRD group versus the DARA-VRD group at 73% versus 49%. Response rates were excellent in both induction groups. Prior to transplant, in the DARA KRD group, all patients had achieved at least a VGPR. In the DARA VRD group, 78% achieved at least a VGPR. And at best post-transplant response, all the DARA KRD patients had achieved at least a VGPR and 73% achieved a CR. In the DARA VRD group, 99% achieved at least a VGPR and 77% of patients achieved a CR. None of these differences were statistically significant. MRD negativity was achieved by approximately 40% of both groups at best post-transplant response. After approximately 19 months of follow-up, the median progression-free and overall survival were not reached in either group. For patients who got DARA-KRD, the two-year progression-free survival and overall survival were 100%. For patients who got DARA-VRD, the two-year progression-free survival rate was 86%, and the two-year overall survival rate was 93%. We performed a propensity score model using inverse probability weights and found that the type of induction regimen was not associated with either progression-free or overall survival. Receiving at least four induction cycles was associated with improved progression-free survival also in the adjusted model. Post-transplant maintenance was associated with a trend towards improved overall survival. Non-relapse mortality at day 100 and at one year after transplant were 0% in both groups and all deaths were related to disease progression. Some of the limitations of the study include a relatively small cohort, especially in the DARA-KRD group, and also a relatively short follow-up. But overall, our real-world retrospective comparison does demonstrate that DARA-KRD and DARA-VRD induction both achieve a high rate of deep response and comparable short-term outcomes in transplant-eligible newly diagnosed myeloma. The second abstract I would like to talk about is about the safety and efficacy of DARA-VRD induction and autologous transplants in patients aged 70 years or older. So the GRIFFIN and PERSEUS clinical trials evaluated the Dara-VRD induction regimen in transplant-eligible myeloma patients and showed excellent results. However, both trials excluded patients over the age of 70, limiting the generalizability of these findings to older adults. And that’s a population where myeloma is most commonly diagnosed. So we conducted a retrospective study to evaluate the outcomes of patients aged 70 years and above with newly diagnosed myeloma who were treated with DARA-VRD induction followed by autologous transplant. We included consecutive patients transplanted at our center between 2021 and 2024, and patients were certified by age at transplant. Those aged 70 years or above were considered the older group and patients less than 70 years of age were considered the younger group. We included a total of 125 patients. That’s 27 patients in the older group and 98 patients in the younger age group. Most baseline characteristics were similar between the two age groups. A higher proportion of patients in the younger age group had a maximal lenalidomide dose of at least 20 mg during induction, 85% compared to 52% in the older age group. Younger patients more often received busulfan melphalan conditioning for transplant at 30% compared to 7%. Response rates before and after transplant were similar between the two age groups with all patients in the older age group achieving at least the VGPR at best post-transplant response compared to 99% in the younger age group. CR rates at best post-transplant response were also similar between 77 and 78% for both age groups. Time to neutrophil and platelet engraftment was similar between the two age groups. After a median follow-up of 19 months, again the median progression-free and overall survival were not reached in both age groups. At two years, the progression-free survival for the older age group was 78% and for the younger age group 89%. The two-year overall survival was 92% in the older age group and 93% in the younger age. Using inverse probability weighting adjusted analysis, there was no significant difference in either progression-free or overall survival. In this study, we also did not observe any non-relapse mortality events in either group. Four patients developed second primary malignancies, all in the younger cohort. Our findings suggest that in appropriately selected older adults, autologous transplant following DARA-VRD induction remained safe, feasible, and associated with excellent short-term outcomes.

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