The Determination Trial Impact on Upfront (vs Delayed) Autologous Stem Cell Transplantation for Transplant-Eligible Newly Diagnosed Multiple Myeloma

Abstract

Background: Following the completion of induction therapy for newly diagnosed multiple myeloma (NDMM) patients who are transplant-eligible, autologous stem cell transplantation (ASCT) consolidation with high-dose melphalan followed by lenalidomide maintenance therapy is considered standard of care. However, accumulated evidence of significant benefit and deep responses to newer induction therapies that contain combinations of immunomodulatory drugs and proteasome inhibitors have raised questions about the role as well as timing (upfront vs delayed) of ASCT consolidation in the initial treatment of ASCT-eligible NDMM. DETERMINATION is a phase III clinical trial (NCT01208662) that randomly assigned transplant-eligible NDMM patient to treatment with lenalidomide, bortezomib, and dexamethasone with and without an ASCT consolidation, followed by lenalidomide maintenance until progression. The present study surveyed oncologists and hematologists to evaluate their perceptions of the DETERMINATION trial and the benefits and barriers of integrating ASCT into 1L therapy for transplant-eligible NDMM. Methods: In July 2022, U.S.-based oncologists were invited to attend a live meeting to discuss abstracts presented at ASCO 2022. Demographics data were collected in a premeeting survey. The perceptions and reactions of these providers to abstract data, including an abstract detailing the findings from the DETERMINATION trial, were captured via audience response system (ARS) technology. Not all participants answered every question. Responses were aggregated and analyzed using descriptive statistics. Results: Among the 52 participants who attended the live meeting, 79% (n=41) identified as community providers; these providers reported that they see an average of 20 patients on clinic days. Ninety percent (n=45) of the participants who were responders to the DETERMINATION trial data (n=50) indicated that they treat NDMM. After reviewing the trial data, slightly less than half of providers (42%) reported that the data were compelling enough to increase the use of ASCT in the 1L for patients with transplant-eligible NDMM. Of those respondents who treat NDMM, three-quarters were likely to give lenalidomide maintenance therapy until disease progression as opposed to a fixed duration of maintenance therapy. We also found that a lack of overall survival (OS) benefit was a major drawback in DETERMINATION results for most respondents; specifically, when queried on the top limitation of the trial, 73% of respondents (n=33) chose lack of significant OS data. Finally, when making decisions on triplet regimens in multiple myeloma, OS and progression-free survival (PFS) benefits were reported as treatment decision drivers by 44% and 23% of respondents who treat NDMM, respectively. Conclusions: Overall, our data show that OS (which was not a primary endpoint in DETERMINATION) is viewed as the most significant factor when considering 1L treatment decisions in NDMM, and less than half respondents indicated that PFS (a primary endpoint in DETERMINATION) persuaded them to increase their use of upfront, vs delayed, ASCT in their patients with transplant-eligible NDMM. Future research by the Cardinal Health Specialty Solutions will aim to clarify various aspect of novel therapies for NDMM including quadruplet 1L therapy, other anti-CD38 antibody upfront usage, minimal residual disease, and their respective impacts on the choice of upfront (vs delayed) ASCT consolidation in the 1L setting.