BMS publishes 'modest' multiple myeloma survival data on heir to Revlimid, Pomalyst

Bristol Myers Squibb has reported full phase 1 data on one of its successors to Revlimid and Pomalyst. An outside expert called the multiple myeloma survival data “modest,” but the potential for the therapy, mezigdomide, to find a place in combination therapies is spurring hopes heading into phase 3 readouts. 

BMS shared an earlier cut of the data, which tracked patients through to May, late last year. The figures shifted a little, both for and against mezigdomide, in the New England Journal of Medicine paper posted Wednesday. The paper covers outcomes in recipients of mezigdomide, a cereblon E3 ligase modulator created in light of insights into the mechanism of thalidomide analogues, up to mid-September. Subjects had received at least three prior lines of treatment, including Revlimid and Pomalyst. 

The final median duration of response (DoR) and progression-free survival (PFS) are shorter than the preliminary data released last year. DoR fell from 8.3 months to 7.6 months. PFS slipped slightly, falling from 4.6 months to 4.4 months. Overall survival data remained immature as of the September cutoff. In an accompanying editorial, Jake Shortt, a professor at Monash University, called the PFS “modest.”

Response rates ticked up between the two looks at the data. The overall response rate rose from 40% to 41%, while the proportion of participants experiencing a very good partial response climbed from 18% to 20%. The data leave unanswered questions about whether mezigdomide can find a place in the changing multiple myeloma landscape.

Late-line treatment of multiple myeloma has changed since Celgene began the mezigdomide clinical trial in 2018. Over the past two years, Johnson & Johnson has won approval for a pair of bispecific T-cell engagers, Tecvayli and Talvey, and a CAR-T cell therapy, Carvykti, in people who have received four or more lines of therapy, by linking the treatments to response rates upward of 65% and “game changing” PFS.

The authors of the mezigdomide paper note the efficacy of cell therapies and bispecifics but caution that the “therapies may not be available or appropriate for all patients, and the risk of severe toxic effects such as cytokine release syndrome” may outweigh the potential benefits in some patient populations.

“Oral regimens such as mezigdomide and dexamethasone can readily translate a potential clinical benefit into real-world practice, especially among patients with limited access to specialized hospitals, since patients do not have to be hospitalized to receive these treatments,” the authors wrote.

BMS has identified mezigdomide as a potential replacement for its own Pomalyst in combinations aimed at patients who have received one to three lines of therapy, including Revlimid. A phase 3 trial in that setting got underway 11 months ago. BMS is also studying the effect of adding mezigdomide to Amgen’s Kyprolis and dexamethasone in a second phase 3 trial that began enrolling patients earlier this year.