TOPLINE

Mezigdomide in combination with carfilzomib and dexamethasone more than doubled the median progression-free survival (PFS) compared with carfilzomib-dexamethasone in patients with relapsed or refractory (R/R) multiple myeloma, though rates of grade 3 or 4 adverse events, including infections, were higher with the mezigdomide triplet regimen. 

METHODOLOGY

• As anti-CD38 antibodies and lenalidomide have moved into frontline and maintenance therapy for multiple myeloma, an increasing number of patients relapse with disease refractory to one or both agents, creating a growing need for effective treatment options in the relapsed setting.
• Carfilzomib-dexamethasone is a common combination backbone in this setting. In the phase 3 SUCCESSOR-2 trial, researchers evaluated whether adding mezigdomide to carfilzomib-dexamethasone could improve outcomes compared with carfilzomib-dexamethasone alone in this patient population.
• The open-label randomized controlled trial included 479 patients with R/R multiple myeloma; 288 received mezigdomide (up to 1.0 mg orally on days 1-21) plus carfilzomib and dexamethasone while 191 received carfilzomib-dexamethasone.
• Overall, patients had received a median of two previous lines of therapy; all had prior exposure to an anti-CD38 antibody and lenalidomide, 92% were triple-class-exposed, and most were refractory to anti-CD38 antibodies, lenalidomide, or their last line of therapy.
• The primary endpoint was PFS; secondary endpoints included overall survival, complete response or better, very good partial response or better, and overall response. The median follow-up duration was 10.6 months.

TAKEAWAY

• Mezigdomide-carfilzomib-dexamethasone reduced the risk for disease progression or death by 52% compared with carfilzomib-dexamethasone (hazard ratio [HR], 0.48; P < .0001); the median PFS was 18.0 months with mezigdomide-carfilzomib-dexamethasone vs 8.3 months with carfilzomib-dexamethasone. The benefit was seen across subgroups, including patients aged 75 years or older, those with high-risk cytogenetics, those with soft tissue plasmacytomas, and those refractory to anti-CD38 antibodies or lenalidomide.
• A complete response or better was achieved in 27% of patients who received mezigdomide-carfilzomib-dexamethasone compared with 9% of those who received carfilzomib-dexamethasone, with very good partial responses or better in 60% and 31% of patients, respectively.
• The overall response rate was 80% with mezigdomide-carfilzomib-dexamethasone compared with 53% with carfilzomib-dexamethasone. At the interim analysis for overall survival, 62 deaths occurred in the mezigdomide-carfilzomib-dexamethasone group and 51 in the carfilzomib-dexamethasone group (HR, 0.79; 95% CI, 0.54-1.15), predominantly due to disease progression.
• Adverse events of grade 3 or 4 occurred in 84% of patients who received mezigdomide-carfilzomib-dexamethasone vs 56% of those who received carfilzomib-dexamethasone, with neutropenia (61% vs 9%) and infections (34% vs 16%) being most common. Treatment-related grade 5 adverse events occurred in 3% vs 1% of patients.

IN PRACTICE

“Mezigdomide-carfilzomib-dexamethasone showed a significant PFS benefit as early as first relapse” in this patient population, the authors wrote.

SOURCE

The study, led by Meletios A. Dimopoulos, MD, Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Greece, was published online in The Lancet.

LIMITATIONS

The follow-up was relatively short (median, 10.6 months), limiting assessment of long-term durability and overall survival. The study compared mezigdomide-carfilzomib-dexamethasone with carfilzomib-dexamethasone alone rather than with another contemporary triplet regimen, limiting direct comparisons with some currently used treatment approaches. The population excluded patients with prior carfilzomib exposure, which might have limited the generalizability of these results. Additionally, high-risk cytogenetics were defined using the criteria in place when the trial was designed, rather than the newer risk stratification system from the International Myeloma Society and International Myeloma Working Group.

DISCLOSURES

The study was funded by Bristol Myers Squibb. Dimopoulos disclosed receiving consulting fees from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, GSK, Janssen, Menarini, Regeneron, Sanofi, Swixx, and Takeda; honoraria from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, GSK, Janssen, Menarini, Regeneron, Sanofi, Swixx, and Takeda; and travel support from Amgen, Bristol Myers Squibb, Janssen, and Takeda. Seven authors declared being employed with Bristol Myers Squibb and owning stocks in it. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.