Optimizing Supportive Care for Talquetamab Adverse Events in Myeloma
During a live event, Alfred L. Garfall, MD, discussed the dose adjustments and supportive care for toxicities seen with talquetamab in multiple myeloma.
Alfred L. Garfall, MD
Patients with relapsed/refractory multiple myeloma sometime require novel therapies after they exhaust standard treatment options. Alfred L. Garfall, MD, director of autologous hematopoietic stem cell transplantation, section chief of myeloma, hematology-oncology, and associate professor of medicine (hematology-oncology) at the Hospital of the University of Pennsylvania, discussed talquetamab (Talvey), a GPRC5D–directed therapy, at an in-person Case-Based Roundtable meeting in Philadelphia, Pennsylvania. Garfall highlighted strategies to manage adverse events, including dose reduction, schedule modification, and supportive care to improve patient tolerability while maintaining therapeutic benefits.
CASE SUMMARY
- A 72-year-old man was diagnosed 6 years ago with multiple myeloma, 60% plasma cells, and translocation 14;20.
- Medical history: respiratory infections (2 episodes of pneumonia, and multiple episodes of bronchitis over prior 10 years)
- The patient received 5 prior line of therapy, most recently B-cell maturation antigen (BCMA)–directed CAR (chimeric antigen receptor) T-cell infusion.
- He now presented with progressive disease (increased free light chain, creatinine 2.3 mg/dL)
- ECOG performance status: 2
- Talquetamab was initiated via step-up dosing (800 mcg/kg every 2 weeks).
- During admission, he experienced grade 1 cytokine release syndrome (CRS) after the second step-up dose.
- He also reported altered taste and dry mouth during step-up dosing.
- By end of the first month of treatment, the patient achieved stringent complete response (sCR), but is experiencing the following adverse events (AEs):
- Oral: complete loss of taste and dry mouth
- Skin: dry skin, skin exfoliation on hands and feet
- Nails: ridging and peeling
Targeted OncologyTM: What do you think of the toxicities seen for the patient with relapsed/refractory multiple myeloma given talquetamab in MonumenTAL-1 (NCT03399799)?
Alfred L. Garfall, MD: The toxicities sometimes start during the step-up dosing; patients are already starting to experience especially the oral and taste toxicity. CRS is very common. It mirrors the response rate, so there was 77% any-grade CRS, very close to the response rate, and very rarely grade 3 or 4. Time to onset is about a day after whatever dose is causing it. It always resolves and lasts for a day or so. Immune cell-associated neurotoxicity syndrome is pretty rare at 7.7% incidence, and almost all low grade. Encephalopathy syndrome also very readily resolves. The infection profile with talquetamab is more, I think, the infection profile of the typical patient with relapsed/refractory myeloma at 64% incidence, 20% or so grade 3 or 4.1,2
I would say the clinical output of the oral and taste toxicity, aside from the patient not feeling well, is weight loss. Forty percent of patients experience weight loss; that weight loss is evident within the first couple months of therapy, and it is very dose responsive. I think the only surefire way to reverse some of this toxicity is to hold the drug. Responses happen very quickly, and so what we're doing in practice is getting patients into a response and backing off on the frequency, and most of the patients that we have on long-term dosing are receiving the drug every 4 to 8 weeks.
Dysphagia, dysgeusia, and dry mouth go along with the oral and taste toxicity, in 70% of patients. So not all patients get this, but most patients do. Rash is in 35% or so, and very rarely grade 3. This does tend to respond well to topical therapies, especially topical corticosteroids. Nail-related adverse events, about half of patients have these, and it's like a pitting and peeling of the nail, and can progress to complete onycholysis, so separation and detachment of the nail bed. It's not painful, actually; it's unsightly, but patients don't mind very much. Patients mind much more the oral and taste toxicities. The nails look a little funny, but it doesn't bother them very much.
Do you hold talquetamab and then resume when it resolves in some of these situations?
If you hold it long enough, it tends to resolve. It does take weeks to months to resolve, so most of us are getting some doses in before it's completely resolved. But it is a continuum, though, so you do get some benefits symptomatically from lowering the dose intensity, even if the symptoms don't completely resolve.
Very few patients in the trial discontinued the drug due to AEs, and even very few patients dose reduced. Although I have to say, in our practice, we're doing a lot of dose reduction or dose deintensification for these AEs. They tend to be dose responsive.
CASE UPDATE
- The following supportive care was provided to help the patient with AEs:
- CRS (grade 1): 1000 mg acetaminophen
- Dermatologic: heavy moisturizing cream; ammonium lactate 12% lotion to hands and feet twice daily; nail hardener, topical vitamin E oil, triamcinolone 0.025% ointment
- Oral: Dexamethasone/nystatin oral rinse; diet changes; dose reduction (cycle 6, 800 mg dropped to 400 mg); schedule modification (monthly dosing)
- He remained in a sCR on monthly dosing. His taste changes were intermittent and grade 1 or less.
- Skin exfoliation resolved during cycle 2
- Nail changes continued
Have you used these methods for oral AEs in your practice?
For oral toxicities, what we found is that reactive use of dexamethasone rinses is not very effective. But I heard from a colleague at Mount Sinai, where they've given a lot of this drug, [that] giving dexamethasone rinses during the step-up dosing—which makes sense is that's where this starts—does help prevent the onset of the oral toxicities. This is something I've started to do with a couple patients in our practice. Most important is the dose reduction and the schedule modification. That's what makes those toxicities more tolerable. Our longest patient who's been on this is approaching 3 years from one of the clinical trials, and she still has some symptoms. She comes in once a month, gets her treatment, continues in a complete response, and was able to live life with, I would say, mild toxicity.
[For dysgeusia], patients will, in my experience—there are certain foods that really work. It's patient by patient, but they'll home in on certain tastes that still manage to get through for whatever reason, and they'll try to double down on those tastes. One patient said they don't know the difference between good and bad food. They can still taste it but can't discriminate tasty food from unpleasant.
What late toxicities were seen in MonumenTAL-1 for these patients?
If we think about later toxicities like infections, most patients develop infections at some point, but there were pretty low rates of grade 3 and 4 infections and very low incidence of opportunistic infections.3 [MonumenTAL-1] looks more like a conventional relapsed/refractory myeloma population for late toxicities. I think these are the kind of numbers you would get with any like triplet or quadruplet regimen in relapse/refractory disease. There was a fair amount of hypogammaglobulinemia, relatively. On these trials, there was not very good adherence in the beginning to introduce immunoglobulin prophylaxis. So very few patients got immunoglobulin prophylaxis, and that may inflate the infection instances on the trial compared with what we see in the real world where we're a little bit more aggressive about that prophylaxis.
