Can an MRD-Adaptive Study Design Help to De-escalate Therapy for Multiple Myeloma?
Posted: Thursday, August 5, 2021
During the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Benjamin Avi Derman, MD, of the University of Chicago, Illinois, and colleagues reported the results of their interim analysis of a minimal residual disease (MRD)-adaptive trial of combination therapy with the monoclonal antibody elotuzumab, the proteasome inhibitor carfilzomib, the immunomodulatory agent lenalidomide, and the corticosteroid dexamethasone (Elo-KRd) in patients with newly diagnosed multiple myeloma (Abstract 8011). These investigators met their primary endpoint and observed that when combined, these agents displayed consistent tolerability with the known toxicities of the agents alone.
“With longer follow-up, the study results may validate that a minimal residual disease–adaptive design for de-escalation of therapy in multiple myeloma can generate deep responses while reducing treatment exposure,” the investigators stated.
This phase II study enrolled 44 patients with newly diagnosed multiple myeloma who received 12 cycles of Elo-KRd. Individuals who were eligible for autologous stem cell transplantation were allowed to undergo collection after the fourth cycle and then continue treatment. Participants who converted from MRD positivity to negativity between cycles 8 and 12 were administered 6 additional cycles; patients with MRD positivity after cycle 12 received an additional 12 cycles.
Of the total, 39 patients were evaluable for response. The median patient age was 62, with 23 individuals expressing high-risk cytogenetic abnormalities; 34 patients had trackable MRD. By the end of cycle 8, next-generation sequencing identified a stringent complete response of 58% and/or negative MRD.
The median follow up was 24 months, with an estimated 2-year progression-free survival and 2-year overall survival of 87% and 89%, respectively. There was no disease progression observed in patients who were MRD-negative after cycle 8, including six individuals who had high-risk cytogenetic abnormalities. Treatment-emergent adverse events affected 89% of patients, with serious adverse events being reported in 30 individuals. The most common adverse event was pneumonia (14%), and one patient had a grade 5 myocardial infarction.
Disclosure: Dr. Derman reported no conflicts of interest. For full disclosures of the other study authors, visit coi.asco.org.