ASCO 2024: Quadruplet vs Triplet Regimen for Newly Diagnosed Transplant-Ineligible Multiple Myeloma

By: Julia Cipriano, MS
Posted: Tuesday, June 25, 2024

According to Xavier P. Leleu, MD, PhD, of the Université de Poitiers and Centre Hospitalier Universitaire de Poitiers, France, and colleagues, the addition of the proteasome inhibitor bortezomib to the monoclonal antibody isatuximab plus lenalidomide and dexamethasone appeared to significantly deepen responses, including an increase in undetectable measurable residual disease (MRD), for newly diagnosed patients with transplant-ineligible multiple myeloma. These results from the multicenter phase III BENEFIT/IFM2020-05 study, which were presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 7501), seem to support the quadruplet regimen as a new standard of care.

“CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone for newly diagnosed transplant-ineligible multiple myeloma, and it is considered the current standard of care,” the investigators commented. “The best treatment combinations are important in [this clinical context], as outcomes worsen with successive lines of therapy.”

The investigators thus sought to improve the current standard of care, randomly assigning 270 nonfrail patients aged 65 to 79 (median age, 73.2 years) to receive isatuximab plus lenalidomide and dexamethasone with or without bortezomib. Stratification factors included age, the presence of high-risk cytogenetics, and the treatment center.

The 18-month rate of undetectable MRD at a sensitivity threshold of 10^-5 cells was found to be significantly higher with vs without bortezomib (47% vs 24%; odds ratio = 2.96; P < .001). According to the investigators, the MRD benefit was consistent across subgroups. At a median follow-up of 21.2 months, 12% of the patients had relapsed, and 7% had died; no significant differences were observed between the arms. The addition of a reduced-intensity weekly schedule of bortezomib did not appear to significantly impact the relative dose intensity of the triplet regimen. More patients treated with vs without bortezomib experienced a neurologic adverse event of grade 2 or higher (33% vs 20%).

Disclosure: Dr. Leleu reported no conflicts of interest. For full disclosures of the other study authors, visit coi.asco.org.

2024 ASCO Annual Meeting

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