BMS mezigdomide, iberdomide to transform multiple myeloma treatment landscape: GlobalData

The latest results from a Phase II study highlight the potential of an all-oral combination therapy, featuring Bristol Myers Squibb’s (BMS) cereblon E3 ubiquitin ligase modulator (CELMoD) mezigdomide and dexamethasone in treating patients with triple-class-refractory multiple myeloma (MM). Consequently, the sales of mezigdomide and iberdomide are expected to increase significantly, amid the shifting dynamics within the MM treatment market, forecasts GlobalData.

According to GlobalData’s analyst consensus forecast, the sales for mezigdomide and iberdomide are predicted to reach $125 million and $389 million, respectively. With Revlimid recently going off patent and sales expected to plummet, BMS hopes these therapies could take their place, but there is plenty of competition in the refractory MM space.

Israel Stern, Oncology & Hematology Analyst at GlobalData, comments, “CELMoDs, including iberdomide, are more potent than the immunomodulatory drugs (IMiDS) Revlimid and Pomalyst traditionally used in earlier lines of MM therapy. Mezigdomide is suited for patient’s refractory to the IMiDS, many of whom also received prior BCMA-targeted therapies. In the study, 41 per cent of the 101 patients dosed responded; the median duration of response was 7.6 months, and the median progression-free survival (PFS) was 4.4 months.”

The common adverse events (AEs) observed included neutropenia in 77 per cent of patients and infections in 65 per cent of patients, 35 per cent of which had grade ≥3 but the AEs were proven to be reversible.

Before this readout, there were concerns amongst the key opinion leaders as to the low blood counts observed for patients on this doublet regimen.

Stern continues, “This remains a bit worrisome, as patients receiving IMiDs in refractory settings typically receive them as part of a triplet combination with an anti-CD30 antibody or with a proteasome inhibitor. So, this is something to look out for if physicians wish to combine these treatments.”

In the last two years, novel therapies such as bispecific antibodies Tecvayli and Talvey as well as CAR-T Carvykti have entered the market and have shown durable responses and strong PFS rates.

Stern concludes: “It is reasonable to question where a modest drug such as mezigdomide will fall on the treatment landscape. The good news is that while those novel therapies may be more effective, they may not be suitable for all patients due to toxicity or the logistics of accessing specialised hospitals providing these therapies. An all-oral regimen will have its place in real-world practice.