Managing Oral Toxicities Among Patients With R/R MM Receiving Talquetamab Therapy

Beth Faiman PhD, MSN, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, provides expert insight on tactics and considerations for managing oral toxicities seen with GPRC5D bispecific antibody talquetamab treatment among patients with relapsed/refractory (R/R) multiple myeloma (MM), highlighting data from MonumenTAL-1.

Transcript:

Hello, my name is Beth Faiman. I am a nurse practitioner at the Cleveland Clinic in Cleveland, Ohio. I'm pleased today to be discussing management considerations for oral toxicities associated with talquetamab, which is one of the new [FDA-approved] treatments for multiple myeloma.

The thing about talquetamab is, first of all, multiple myeloma is a cancer of the bone marrow plasma cells, and plasma cells are programmed to survive. So many of our patients will go through induction and consolidation and be in a nice remission after a standard therapy. But after 1, 2, or 3 prior lines of therapy, they become ultimately relapsed and refractory to the disease because these plasma cells are programmed to survive.

Talquetamab is a bispecific antibody that's humanized against CD3, which is a T-cell service antigen, and a human G protein coupled receptor family C group 5 (GPRC5D) tumor-associated antigen. What happens is it takes a helping hand and binds to cause cell death of the myeloma cells. Now this is an orphan receptor, and this is a little bit different than some of the other drugs to treat myeloma because it has some other off-target effects as it's expressed on tumor cells to crosslink and redirect those T-cells to become fighters against the cancer.

Talquetamab was approved by the US Food and Drug Administration [(FDA)] for the treatment of patients with relapsed/refractory myeloma who've had 4 prior lines of therapy and they had to have drugs such as proteasome inhibitor, that's your carfilzomib and bortezomib, immunomodulatory drugs like lenalidomide and an anti-CD38 monoclonal antibody like daratumumab or isatuximab.

The study that gained the FDA approval was MonumenTAL-1. That was an open-label single arm study, So everybody got the drug with varying subcutaneous doses, starting at 0.4 milligrams per kilogram weekly and 0.8 milligrams per kilogram every other week. The neat thing about this study is that it did show that you didn't have to give the drug every week, and it did show a nice response rate. Think about those patients of yours that have had lots of prior therapies and now we just can't get them back into remission. Their overall response rates are over 70%. It doesn't matter if you've had 1, 2, 3, or 4 prior therapies—it's likely that this therapy will be effective.

There was a poster presented at the Oncology Nursing Society  (ONS) Conference this year, which talked about adverse events. From my personal experience, and I've treated many patients with this drug, it tends to be the oral [and dermatologic] toxicities that are biggest concern in this study. Management of these things is important because this is an effective therapy in patients that have had lots of prior therapies. I've had people that have been on this drug for a long, long time. The key is to give effective nursing consideration strategies—or whatever domain you're in—if you're a physician provider, nurse practitioner, PA.

Dysgeusia is the alteration in the quality and sensitivity of taste changes. That's what I think is one of the number 1 things that bother patients when they have this drug. You can also have dysphasia, which is difficulty swallowing, where they just feel like the food can't get down as easily. You can also have dry mouth or xerostomia. That's another thing that we've seen and what was reported at the Oncology Nursing Society meeting. These happen quite frequently. We worry about the acute effects of giving the drugs such as cytokine release syndrome (CRS) or [immune effector cell-associated neurotoxicity syndrome] (ICANS), which we won't go into detail here because we're talking about management strategies of the oral toxicities. But those are the long-term things we have to deal with.

Now, in my experience, some of the strategies that have been very effective at helping our patients is number 1, setting expectations. Let your patients and their caregivers know that this is going to be an issue. Most patients in the study did experience some types of taste alterations, and that's okay.

We want the drug to be effective. Of course, we want it to be safe, and we want them to take the drug because we know it's likely to work if we can keep them on it. Giving them mouthwashes and mouth rinses is really important in my experience and what was reported in the poster. Mouth rinses will also be very helpful in rinsing, baking soda and salt water before and after eating.

We recommend to eat bland foods, kind of like if they have a transplant. We recommend our patients not to eat something they really like. If you love pizza, don't eat that. Especially it's maybe a little bit more greasy, which might turn you off, or the sauce in the pizza might turn you off. Eating bland food, small bites, soft foods can help as well. Caffeine and alcohol can dry out [and lead to] oral mucositis, so we tend to recommend not to do that.

Sugarless gum and hard candies have been shown to be helpful. For my patients I do recommend dexamethasone rinses. There's some discussion about whether or not that is effective, but definitely giving them nystatin because they're at risk for thrush, due to the immunosuppression from the treatment. Also look in their mouth. Do they have white patches? Do they have budding yeast, or is it just red? Because these are all signs of oral thrush. Also, and this should go without saying, try to avoid tobacco use because many of our patients have been prior or current smokers. Try to tell them to limit or avoid or even stop. Finally, I think keeping the lips nice and soft is really helpful. We tell them to put lip balm on and not to stress.

We get them in with a nutritionist as soon as we can. I write prescriptions for Ensure and Boost nutritional supplements and encourage them to do the best that they can. But if this really has become an issue, then we can hold the treatment or dose delay. A little bit of talquetamab is better than no talquetamab. We want them to stay on effective therapy. I think that's the important highlight is that the longer you stay on this, the toxicities are less likely to be an issue.

Community practitioners are important to our patient care because most of our patients aren't treated at large medical centers. Most of our patients are treated in the community near their places of residence, where it's easier to get in, and you don't have to pay for parking. For community practitioners, it can be a little bit concerning when you have a patient who's had many prior therapies.

I like to start the relationship with the patient and the medical center early on, maybe that first diagnosis where they're referred for stem cell transplant. The larger hospital centers should form that relationship earlier with the community practices and [tell them to] stay connected with these folks. Because oftentimes, even though it's available in the community, patients need to be started in a large hospital medical center for their step-up dosing, because we give them a short hospital stay it can vary according to the person—in most institutions. Some do outpatient dosing, but because cytokine release syndrome and ICANS are 2 main considerations that we worry about, so they have to be admitted and started on their step-up doses.

After they are then discharged, we can have a handoff to the community where we say, make sure that they're on this appropriate supportive care for their skin and nail toxicities. Make sure that they're on antibiotic prophylaxis against [pneumocystis jirovecii pneumonia] (PJP) pneumonia, if it's appropriate. Make sure that they're on shingles prophylaxis for acyclovir.

Then we give them a list of the things to consider so that the community practice is watching for these side effects. I think the important thing is that these are all new drugs, and it does take some time for community to feel comfortable to refer patients or start them on in the community. It also takes some time for the hospital, large hospital systems, to feel comfortable to send them back. But establishing that relationship also brings the patient in. The patient will then comfortable with that treatment team.

Again, the treatment toxicities will lessen over time. I have patients that have been on this for many, many months to years, so I did not firsthand participate in the MONUMENTAL-1 study, but I have treated over 80 patients with this drug. So we have a good amount of experience. Not everybody experiences these side effects, but most people do.

If you can hold the doses, reduce the doses—there was an abstract at ASH last year by Dr. Chari and colleagues and some other subsequent follow-up papers that suggests that if you hold the dose and if you've restart it, but then you're getting a nice remission or very-good partial response (VGPR) or you're getting a nice response, then you can go to monthly administration. Below dose is better than no dose. Listen to your patient, ask from about the toxicities and try to do the best you can about supportive care, because it's really about keeping the patient on the drug as long as you can.

Source:

S Shenoy, S Leahey, D Catamero, et al. Management Considerations for Oral Toxicities Associated With Talquetamab, a GPRC5D×CD3 Bispecific Antibody, in Patients With Relapsed/Refractory Multiple Myeloma: Experience in MonumenTAL-1. 49th Annual Oncology Nursing Society (ONS) Congress. Washington, DC. April 24-28, 2024.