IMS 2025: Navigating Toxicities and Improving Care in Novel Myeloma Therapies

Rahul Banerjee, MD, FACP, assistant professor of medicine at the Fred Hutchinson Cancer Center in Seattle, Washington, continued his conversation with Pharmacy Times® at the 22nd annual International Myeloma Society (IMS) meeting and exposition in Toronto, Canada, discussing key safety concerns with emerging myeloma therapies. These include toxicities associated with GPRC5D bispecifics and CAR T-cell treatments, such as skin, nail, tongue, and neurotoxic effects. He highlighted the evolving role of pharmacists in managing these challenges, particularly in preventing cytokine release syndrome, infections, and immunoglobulin deficiencies. Banerjee emphasized that pharmacists are also leading efforts to optimize treatment through prophylactic strategies, supportive care, and dose adjustments to improve safety while maintaining efficacy.

Pharmacy Times: What key safety or toxicity considerations should pharmacists and other healthcare providers keep in mind as these therapies move closer to clinical use?

Rahul Banerjee, MD, FACP: I think GPRC5D is the biggest one that all of us are learning about. Physicians, pharmacists, and nurses are all learning at the same time. Our pharmacist colleagues have been instrumental in managing many of these toxicities, so I think that will probably be the biggest one.

GPRC5D bispecific talquetamab is already here. I still don’t really know how to manage toxicities. I’m still learning myself in terms of the skin, nail, tongue, and even cerebellar toxicity that can happen with this drug, the GPRC5D CAR T, like Arlo. Just as an example, it will hopefully start getting into more practices, either through clinical trials or approval.

The tongue, skin, and nail toxicities aren’t quite as bad because the kinetics of CAR T are different than those of a bispecific antibody. You’re not targeting the antigen again and again, just hitting it once. But about 10% of patients can sometimes get cerebellar toxicities, and that is something that we know very little about. We are trying to figure out why that happens. We think it’s because GPRC5D is found in the inferior olivary nucleus. Figuring out why that happens and how to prevent it is a big deal for the field.

Interestingly, with our existing therapy—cilta-cel (ciltacabtagene autoleucel), a BCMA CAR T therapy—our pharmacists are instrumentally involved with many aspects of it. One of the new frontiers we are still exploring, and that data is being presented here, is in CARTITUDE-1 with cilta-cel. Six percent of patients developed Parkinsonism. Thirty-three percent of them are alive, disease-free, and doing well, but 6% developed severe delayed neurotoxicities. The number comes down to maybe 0.6% with CAR T overall, but that’s still too many for me.

There is a lot of interesting data around using drugs preemptively to prevent that. The thought is that if someone’s lymphocyte count is rapidly rising after CAR T, that may indicate rapid CAR T-cell expansion, which could predispose them to CAR T cells infiltrating areas where they should not be, such as the CSF and around the basal ganglia. So, people are using dexamethasone early—not a new drug and not a new toxicity—but a new combination, using dexamethasone just because the lymphocyte count is rising, to help prevent toxicity.

So, I would say to pharmacists and physicians hearing this: stay tuned to the news. There will be an oral presentation here at ASH, and every year we’ll hear more. This is the idea that what we once thought was a good thing—like rising lymphocyte counts—may actually be harmful. Dr. Martin at UCSF always said that when his CAR T-cell patients’ lymphocyte count rose to 55,000, he’d give them a high five because the cells were expanding. Now we know that might be more harm than good. Even identifying it as a toxicity is step one; figuring out how to manage it is step two. We still have work to do.

Pharmacy Times: Looking ahead, how do you see pharmacists playing a role in integrating these new treatments into patient care and optimizing outcomes for those with RRMM?

Banerjee: I think the biggest way our pharmacists have led the charge is in many of our endeavors around bispecific antibodies, so I’ll focus on that for this question.

As people listening are aware, in the U.S. we have teclistamab, talquetamab, elranatamab, linvoseltamab, and more bispecifics in other malignancies. A lot of data is being presented on strategies to make these antibodies safer—preventing CRS, preventing infections with BCMA bispecifics, and preventing skin, nail, hair, and tongue toxicities with GPRC5D bispecifics.

Our pharmacists are instrumental in this. For example, with all bispecific antibodies, prophylactic tocilizumab is something we are still learning how to operationalize, and pharmacists are helping lead the way. If done right, prophylactic tocilizumab means many patients will have great results without CRS and may not even need admission. Some hospitals still do inpatient step-up dosing, but having pharmacists lead the transition to outpatient care—planning tools, medication timing, and management of grade 1 CRS—is critical.

Should we use dexamethasone instead of tocilizumab? Some of the best work on using dexamethasone to treat grade 1 CRS with bispecifics came from a pharmacist, James Davis at MUSC. That’s an important unmet need.

Infections are also an Achilles’ heel for our patients, and pharmacists have been instrumental in keeping us on track with prophylaxis. I would argue that IVIG or subcutaneous immunoglobulin replacement is imperative in the modern era. Many doctors still go by the “400 rule,” only giving IgG replacement if the IgG level drops below 400. We’ve published data and a thought piece saying not to do that. With bispecific antibodies, patients become immunocompromised so quickly that IVIG should be started right away.

The IgG level of 400 is arbitrary and often meaningless because it may be influenced by an M-protein that is not useful. The principle is complicated, but pharmacists can be on the cutting edge: if a patient is on a bispecific, get them on IVIG.

For patients with a lot of toxicities, pharmacists can also help adjust dosing intensity—reducing from once a week to every two weeks or once a month—to maintain efficacy while improving safety. A lot of that work is being led by pharmacists at my institution, Fred Hutch, and I think they are the best equipped to do it because they know these drugs best.