How to Navigate Ramantamig’s Low-Grade Toxicities in Multiple Myeloma

Because ramantamig (JNJ-5322) targets both BCMA and GPRC5D, it carries the distinct toxicity profiles associated with each target, including the infection risk from BCMA engagement, and on-target, off-tumor effects such as taste disturbance, skin rash, and nail changes from GPRC5D engagement. In the TRIlogy-1 trial (NCT05652335), grade 3 or higher infections occurred in about 25% of patients with relapsed/refractory multiple myeloma, which preceded proactive antiviral, PJP, and immunoglobulin replacement prophylaxis. Taste changes, skin, and nail adverse events were common but mostly grade 1, with mean weight loss under 5% and only 1 of 56 patients discontinuing treatment because of skin rash.

Jeffrey V. Matous, MD, a member physician at the Colorado Blood Cancer Institute at Presbyterian St. Luke’s Medical Center, part of the Sarah Cannon Blood Cancer Network, and a clinical professor of Medicine at the University of Colorado Health Sciences Center, who presented these findings at the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition, spoke with CancerNetwork^® about how oncologists should counsel patients on these chronic, low-grade toxicities so they don’t derail adherence over months of therapy.

Transcript:

CancerNetwork: Taste changes, skin, and nail toxicities were common but almost entirely low-grade, with minimal impact on weight loss or discontinuation. How should oncologists counsel patients on these chronic, low-grade toxicities so they don’t derail adherence over months of therapy?

Matous: In the hematology-oncology community, the concerns over targeting BCMA are primarily related to infection risk, and the concerns over targeting GPRC5D, for example with talquetamab-tgvs [Talvey], the bispecific, are the on-target, off-tumor [adverse] effects such as taste disturbance, skin rash, dry mouth, sore tongue, difficulty swallowing, and weight loss.

Let’s address the BCMA aspect first: the infection risk. Fortunately, we’ve learned a lot over the years about how to mitigate infection when targeting BCMA [by] using antiviral prophylaxis, PJP prophylaxis, and routine immunoglobulin infusions. With that, we’ve decreased the rate of grade 3 or worse infections, and on this trial, that was about 25% of the patient population. Recall that this trial enrolled patients on the heels of the [COVID-19] pandemic, so that was a good proof of concept to show that with a triple mitigation strategy, we can decrease grade 3 infections.

With respect to targeting GPRC5D, this is a very daunting thing for both patients and clinicians, and the hope here is that with the trispecific nature of ramantamig, and its novel binding domains, we would see less of the on-target, off-tumor [adverse] effects of targeting GPRC5D. Indeed, we saw that in this trial; there was no weight loss difference between patients who reported taste disturbance vs those who didn’t, and weight loss was less than 5% overall. We saw very manageable taste disturbance and manageable skin rash, although we did have 1 patient out of the 56 who came off study because of skin rash. We still have to be on the lookout for that, but it’s the sense of all the investigators participating in this trial that we are seeing fewer of these GPRC5D-targeting [adverse] effects.

Reference

Matous JV, Varga C, Krishnan AY, et al. Updated safety and efficacy of ramantamig (JNJ-5322) at the recommended phase 2 dose demonstrating feasibility of outpatient dosing in relapsed/refractory multiple myeloma. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Abstract OA-70.