Talquetamab Side Effects: Managing Taste Loss, Hair & Nail Changes in Myeloma 

Dr. Joseph Mikhael: 

We have a new target on the myeloma cell called GPRC5D that we can use to destroy myeloma, but when patients are treated this way, they can develop some unique side effects. How can we best manage those side effects? 

Hi, everybody. Dr. Joseph Mikhael, here, chief Medical Officer of the International Myeloma Foundation. Welcome to the Myeloma Made Simple series where we work hard to make sure the complicated world of myeloma is understandable to everybody. Before I dive into today's episode, let me remind you that the IMF is here for you. We want to help you through this complicated journey. You can call us on the info line. You can visit us at myeloma.org. You can even use our chatbot, Milo, to answer questions 24/7. And of course, we want you to employ this Myeloma Made Simple video series where we take complicated topics and ideas and make them straightforward for patients and their partners so they can understand their treatments and understand their journey in myeloma. 

Today's episode is on GPRC5D-related side effects. I know that's a bit of a mouthful, but GPRC5D stands for a target or for something that sticks out of the myeloma cell. Of course, we know in multiple myeloma, this is a disease of the plasma cell or the cell that makes our antibodies that lives in the bone marrow. Interestingly, these cells have lots of different things that stick out of them, and many of them can be used as targets to destroy the cell. For years, in myeloma, we've used CD38 or BCMA, and now we have this relatively new target of GPRC5D. It's exciting because we want a new way to attack myeloma, and we actually now have a drug that is FDA approved Talquetamab that works to target the GPRC5D. The benefit of targeting GPRC5D is that even when we've exhausted other options and use the other targets, we know that the therapy we use with Talquetamab can be highly effective, giving people a deep and a durable response. 

The challenge is we do see some unique side effects. So to be clear, as a bispecific antibody like we see with other bispecific antibodies and even with CAR T-cell therapy, we see the typical three side effects we always look for, cytokine release syndrome, neurological toxicities, and infections. We see those with this drug Talquetamab, maybe a little bit less on the infection side, which is one of the attractive features to it. But now we do see some unique GPRC5D-related side effects because we know, as I've said, GPRC5D sometimes can exist on other tissues. So there are four other side effects that we have to watch for when patients are being treated with Talquetamab. Let's walk through these four things. 

Number one, we know that people can lose a little bit of their taste. We don't have a perfect antidote for that, but we have learned that if we can keep the mouth moist, if we can optimize their nutrition very often with help from a dietician or from a nutrition consult to see what tastes good, what doesn't taste good, and we take that approach, we've often found that over time those taste buds do come back. Over time, those patients are able to keep eating and eat well so that they don't have long-term effects from that loss of taste. 

The second side effect we can see with Talquetamab is the way it affects nails. And unfortunately, the nails can thin and sometimes even drop off. Now, thankfully, they will grow back and sometimes it may take a few months for that to occur. In the interim, we try to do things like use nail hardeners and moisturizers that can sometimes keep the nails more intact and make the process easier. 

The third side effect we can see from Talquetamab is it can thin hair. For individuals like myself, it may not be as big a deal, but for some people, we can really see a change in their hair. There's no perfect solution to this, but we've learned that if we can keep the hair moisturized, it can keep it stronger and more intact. 

The fourth side effect is rash. Sometimes we see this on the palms of hands or the soles of feet, and this can be quite uncomfortable for patients, but if we moisturize very well and keep the area clean, very often that rash will dissipate. Indeed, for all of these four side effects, they sound rather dramatic, but for the majority of patients, they're more dramatic for the first few months on therapy and then they become easier to manage and they become less severe. 

Overall, one of the things that has helped us reduce the severity of these side effects has been reducing the frequency of dosing of Talquetamab. Typically, the drug is given every other week, but we have learned that we can often go down to once a month and that makes these side effects less. But I should say that there are still some patients, unfortunately, who do have to come off the therapy because of these side effects, but as we've learned to manage them better and use these supportive care tactics, the vast majority of our patients can indeed stay on this drug. 

So we've learned that GPRC5D is a great target on myeloma, that we have a highly effective therapy to be able to take down myeloma in the form of the bispecific antibody Talquetamab, but we have to be aware that there are certain side effects. And when you go into your treatment knowing that these can happen, having an open, honest conversation with your healthcare team about what is happening and what steps we're taking to try and improve them, we know a patient's experience can be better. When you're more aware of what's to come, it's easier to get through these side effects, and more often than not, patients can indeed continue on this Talquetamab therapy and stay in a durable remission for long periods of time. 

Well, I hope this video has been helpful to you as we've thought through the details of GPRC5D-related side effects and how we can manage them when a patient is being treated with Talquetamab. Don't miss the rest of the Myeloma Made Simple series as we try to take the complex themes and concepts of myeloma and make them understandable to you and your care partner.