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IMS 2026 | Update on the MELT-MM study: mezigdomide plus elranatamab in R/R MM
Ja Min Byun, MD, PhD, Seoul National University College of Medicine, Seoul, South Korea, shares an update on the MELT-MM study (NCT06645678), a two-part trial investigating the combination of mezigdomide and elranatamab for relapsed/refractory multiple myeloma (R/R MM). Dr Min Byun highlights that the Phase Ib results demonstrate favorable efficacy outcomes and a manageable safety profile. This interview took place at the 23rd International Myeloma Society (IMS) Annual Meeting in Glasgow, UK.
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Transcript
So the MELT-MM study is a two-part study where we do a phase 1b, which is the part 1, which I’ll be presenting later today. And part 2 study is the phase equivalent of the phase 2 study of the whole schema. So BCMA T-cell engagers have transformed the multiple myeloma treatment paradigm, but even so, they’re not perfect, especially when used alone. One of the problems is that it ultimately leads to T-cell exhaustion, which causes the resistance...
So the MELT-MM study is a two-part study where we do a phase 1b, which is the part 1, which I’ll be presenting later today. And part 2 study is the phase equivalent of the phase 2 study of the whole schema. So BCMA T-cell engagers have transformed the multiple myeloma treatment paradigm, but even so, they’re not perfect, especially when used alone. One of the problems is that it ultimately leads to T-cell exhaustion, which causes the resistance. So our hypothesis was that by adding mezigdomide to elotuzumab, it will be able to enhance T-cell fitness and reverse the T-cell exhaustion, thereby giving us a more durable response and a deeper response. For part one, we were able to screen 15 patients and enroll 15 patients, but out of the 15, one actually progressed during cycle zero and one withdrew consent during cycle zero. So we were able to get the safety and efficacy results from 13 patients and out of the 13 patients the median age at enrollment was 69 I believe and the prior lines of therapy was four and even in that heavily pre-treated patients we were able to achieve an overall response rate of 100%. Very good PR in one patient, and everyone else was able to achieve a stringent CR. So that’s very good news. And out of the 13, MRD results were available in 11 patients. And out of the 11, 10 were MRD 10 to the negative 5 CR, which is very good news. So efficacy-wise, it works brilliantly. And it doesn’t matter whether we use mezigdomide 0.3 or 0.6, and the prior lines of therapy doesn’t really affect the efficacy. That’s very good news. Safety-wise, the most prominent adverse event was actually neutropenia, but it was pretty manageable. It did not lead to febrile neutropenia, which was good news. And the most common non-hematologic toxicity was fatigue, but that was also manageable. One of the interesting things about the MELT-MM study is that we were able to provide evidence that mezigdomide does overcome T-cell exhaustion by attenuating PD-1 upregulation and decreasing TGF-beta expression from patient samples as well as preclinical data. And we were able to show that T-cell fitness is also enhanced, both preclinical data and patient samples. So we’re pretty excited about this combination and we are currently enrolling patients into phase two part or the part two study from Singapore and Korea.
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