Management Considerations for Oral Toxicities Associated With Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma

Samantha Shenoy, NP, University of California San Francisco, discusses considerations for nurses and advanced practitioners managing patients with relapsed/refractory multiple myeloma experiencing oral toxicities after treatment with talquetamab. This guidance was presented at the 2024 Oncology Nursing Society (ONS) Congress in Washington, DC.

Transcript:

Hi, my name is Samantha Shenoy. I'm the research nurse practitioner at UCSF in San Francisco, California, for patients with hematologic malignancies.

What is talquetamab and its indication?

Talquetamab is a T cell redirecting bispecific antibody targeting GPRC5D, which stands for G protein coupled receptor family C, group 5, member D on myeloma cells and CD3 on T cells, thus activating T cells to kill the GPRC5D-expressing myeloma cells.

Talquetamab was approved by the FDA for the treatment of patients with relapsed/refractory multiple myeloma who received at least 4 lines of prior therapy, including a proteasome inhibitor and immunomodulatory agent and an anti-CD38 monoclonal antibody. Talquetamab has shown an overall response rate of greater than 71% in patients with relapsed/refractory myeloma in the MonumenTAL-1 study.

Can you briefly describe the Monumental-1 study?

MonumenTAL-1 is an open-label, single-arm phase 1/2 study of patients with relapsed/refractory multiple myeloma, evaluating the recommended phase 2 doses of subcutaneous talquetamab at 0.4 mg/kg weekly and 0.8 mg/kg every other week.

What background information motivated you and your coinvestigators to describe strategies for monitoring and managing GPRC5D-related oral adverse events (AEs)?

My co-authors and I were motivated to look at the MonumenTAL-1 study and come up with management strategies for some of these oral AEs because of the fact that the oral AEs have such a significant impact on quality of life. So, we wanted to investigate strategies that could help with these different oral AEs, so that we could improve patients’ quality of life while they were receiving talquetamab.

Can you describe the common oral AEs seen in MonumenTAL-1?

The common oral adverse events that we're seeing in the MonumenTAL-1 study were dysgeusia, which is alteration and taste quality, ageusia, which is loss of taste and hypogeusia, which is reduced ability to taste. In addition to these taste alterations, dysphasia was also seen, which is difficulty swallowing, and that's mainly due to dry mouth and dry mouth was another major AE seen, also known as xerostomia.

Table 1 illustrates the summary of oral adverse events associated with talquetamab in MonumenTAL-1. As you can see the incidence of dysgeusia was about 72%, and the time to onset was around 13 to 20 days, and about 38% of these cases resolved and about 0.6% of patients discontinued treatment due to dysgeusia.

In terms of dysphasia, the incidence was about 24% with grade 3 to 4 events about 0.9%. Time to onset was 21 to 29 days and about 65% of these events resolved.

And then, lastly, for dry mouth or xerostomia, the incidence was 36%. The time to onset was around 19 to 26 days and about 39% of these in the cases of dry mouth resolved. I forgot to say that no patients were discontinued because of dysphasia or dry mouth.

Can you explain the recommended management strategies for each of the oral AEs seen with talquetamab?

The management strategies recommended for the oral AEs are really broken down into different interventions for each of the different oral AEs. For example, for dysgeusia, some of the management strategies are rinsing with baking soda and salt rinses before and after eating, and this helps wake up the taste buds.

Another management strategy is using the fat/acid/salt/sweet formula developed by Rebecca Katz to help target what the different tastes are. For example, if something tastes metallic, she he has different recommendations for different mixtures of these different ingredients that you can use to help with a metallic taste. Some other things that you can do are marinating foods in different bases to add more flavor and some other examples of strategies are to avoid eating using metal utensils, for example, if something tastes metallic.

I would say, the dysgeusia, ageusia, and hypogeusia management strategies that are illustrated in this poster really highlight different strategies for each of the different taste alterations. It's really important to identify what the taste alteration is, and then you can target your management strategy for what that actual taste alteration is for each individual patient.

For dry mouth, that's another very common oral AE that you'll see and that patients will complain about and one of the best things they can do is stay really well-hydrated. Rinsing with baking soda and salt water before and after eating is also helpful for this. Interventions, such as eating soft or bland foods that are colder room temperature or adding broth gravy to foods to help moisten foods are important.

It's also important to educate patients about limiting their caffeine and alcohol intake because that can dry out the mouth. There are various dry mouth lozenges or rinses that can be used to help target dry mouth. And another intervention is sucking on sour candies or something tart prior to meals to help stimulate the salivary glands or chewing on sugarless gum, which has xylitol, which stimulates saliva and eating tart food or drinking tart drinks can be other management strategies for dry mouth.

For dysphasia, which is difficulty swallowing, and that's due to dry mouth, some strategies that can be used are cutting foods into bite-size pieces or using a blender or food processor to puree food so it's easier to swallow. And adding high calorie liquids instead of water when cooking to make sure you're getting adequate caloric intake and avoiding meat or dry foods. Also, sitting upright when eating and taking small sips of liquid between bites is also very helpful for dysphagia.

And for weight loss, that is also another concern with these patients due to the fact that they have the taste alteration, the dry mouth, we are seeing patients lose weight. It's really important to educate patients about eating small and frequent meals or snacks, to carry snacks with them at all time, to eat nutrient-dense and calorie-boosting foods or liquids, and to eat fatty fish 2 or 3 times a week. You could also consider an appetite stimulant and stay active, because as we all know, when we're active, it helps to simulate appetite as well.

What general guidance can you provide for nurses educating and managing patients experiencing GPRC5D-related AEs?

Some general guidance for nurses and APPs and physicians caring for these patients is to educate these patients from the very start. Before they've even started, to educate them about the possible AEs and the management strategies that I've mentioned here. For example, at UCSF, we give patients a handout prior to them even starting talquetamab so that they can be empowered to play a role in their care and be ready for the oral AEs that they will experience while getting talquetamab.

And it's really important to work with our nutrition team. So, if someone's really high risk for weight loss, it's good idea to consult nutrition at the beginning and or if someone starts to lose a significant amount of weight while they're on talquetamab, it's also a good idea to consult nutrition. And it's also really important to acknowledge and validate the patient's experience, because food is such an important part of life, and when patients lose their ability to taste, it really affects their quality of life. So, just acknowledging that with patients and providing emotional support while they're going through the treatment is really important.

And another good tip is to consider dose modifications once patients have achieved a response. This could be reducing the dose, delaying, or reducing the frequency. Because data has shown that patients who have a dose reduction after they've achieved a response do not have a compromise and advocacy, and they also have a decrease in the severity of AEs.

Are there any takeaways from this study you would like to close with?

I would say MonumenTAL-1, as you all know, was a pivotal trial that led to FDA approval for talquetamab, and it's really important to also educate patients about the efficacy of the drug. It's a drug that has shown efficacy in heavily pretreated patients and patients who are high risk and have extramedullary disease, so it's really important to as a clinician also remember and remind patients about the efficacy of this drug. And, as I mentioned early earlier, the overall response rates of greater than 71%.

And I think the other thing that's really important is to remind patients that this is not forever, that it may take some time, but symptoms will get better. So, if you can really utilize some of these recommendations and try out some of these recommendations, and talk to your provider about it, just know that it's not forever and that's really important for patients to know.