Elotuzumab-based quadruplet produces durable responses in newly diagnosed multiple myeloma
- Stringent complete response and/or MRD-negativity rate of 58% reported after treatment cycle 8.
- MRD-negativity rate increased to 70% by the end of the study.
- “Novel immunotherapies are here to stay,” editorial authors write.
A quadruplet regimen comprising the monoclonal antibody elotuzumab plus weekly carfilzomib, lenalidomide and dexamethasone conferred a 72% 3-year PFS rate among patients with newly diagnosed multiple myeloma, phase 2 trial results showed.
Data from the study published in JAMA Oncology suggest that use of a minimal residual disease (MRD)-guided regimen can limit treatment exposure while maintaining deepened responses to therapy without the need for front-line autologous stem cell transplant (ASCT), the investigators noted.
Background
Results of randomized studies have shown that quadruplet regimens comprising a monoclonal antibody plus a proteasome inhibitor and immunomodulatory imide drugs have produced deeper responses and superior PFS than triplet regimens in patients with newly diagnosed multiple myeloma, according to Benjamin A. Derman, MD, assistant professor of medicine at University of Chicago Medical Center, and colleagues.
What is not yet known is the optimal combination of these drugs.
“More intensive upfront therapy may allow for shorter courses of therapy and the elimination of ASCT from the front-line treatment paradigm,” Derman and colleagues wrote. “An MRD-adapted treatment approach is rational because it may identify which patients can be administered shorter courses of intensive therapy without compromising efficacy.”
Methodology
Derman and colleagues enrolled 46 patients (median age, 62 years; range, 43-81; 72% men) between July 2017 and February 2021 in phase 2 multicenter study to evaluate the safety and efficacy of elotuzumab (Empliciti; Bristol-Myers Squibb, AbbVie) plus weekly carfilzomib, lenalidomide and dexamethasone in adults with newly diagnosed multiple myeloma.
Study participants received between 12 to 24 cycles of the quadruplet regimen. The researchers determined the duration of therapy by two consecutive MRD-negative results using next-generation sequencing after treatment cycles 8 and 12. Those who achieved MRD-negative status transitioned to maintenance therapy with elotuzumab plus weekly lenalidomide and dexamethasone until they experienced disease progression.
Stringent complete response and/or MRD-negativity served as the study’s primary endpoints. Secondary endpoints included safety, PFS and OS.
Median follow-up was 28.7 months (range, 1.4-50.1 months).
Key findings
The study met its predefined statistical threshold for treatment efficacy, with a stringent complete response and/or MRD-negativity rate of 58% after treatment cycle 8.
The MRD-negativity rate increased to 70% by the end of the study, suggesting a deepening of responses over time, the investigators noted.
Median PFS and OS have not yet been reached.
Researchers calculated an estimated 3-year PFS of 72% for the entire study population that increased to 92% among MRD-negative patients after treatment cycle 8.
Additionally, investigators noted an estimated 3-year OS of 78% for the entire study population that increased to 100% among MRD-negative patients after treatment cycle 8.
The most common hematologic treatment-related grade 3/grade 4 adverse event, neutropenia, occurred in 11% of patients. Other grade 3 or grade 4 treatment-related adverse events included lung infections (13%) and nonpulmonary infections (11%). One patient experienced a grade 5 treatment-related myocardial infarction.
Clinical implications
“In this study [the quadruplet regimen] was associated, at face value, with an impressive MRD negativity/stringent complete response rate of 58%,” Dickran Kazandjian, MD, and Ola Landgren, MD, PhD, of University of Miami’s Sylvester Comprehensive Cancer Center, wrote in an accompanying editorial.
Nevertheless, Kazandjian and Landgren noted that single-arm studies such as the one conducted by Derman and colleagues are limited by the isolation of treatment effect. They said the question of whether the addition of elotuzumab to the treatment regimen had clinical benefit will likely be answered by future results of an ongoing phase 3 trial.
“Regardless of what the future holds for elotuzumab-based combinations, it is clear that the new treatment paradigm of newly diagnosed [multiple myeloma] will incorporate antibody-based quadruplet regimens and that novel immunotherapies are here to stay,” Kazandjian and Landgren wrote. “They are already transforming the lives of patients with [multiple myeloma] and bringing a bright horizon to the treatment landscape.”
References:
- Derman BA, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2022.2424.
- Kazandjian D, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2022.2421.
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