Managing Talquetamab-Related Rash in Relapsed/Refractory Multiple Myeloma

Mary Steinbach, NP, Huntsman Cancer Institute, Salt Lake City, Utah, discusses a case of a 52-year-old patient with high-risk, relapsed/refractory IgA multiple myeloma who progressed after multiple lines of therapy, including autologous transplant and CAR T-cell therapy. With the development of extramedullary disease, talquetamab was initiated, leading to a rapid clinical response. 

Early treatment was complicated by a grade 2 dermatologic toxicity with rash and blistering. This case highlights practical strategies for managing talquetamab-related skin toxicity while maintaining therapy in a heavily pretreated patient.

Transcript: 

Hello, my name is Mary Steinbach, I am a nurse practitioner at Huntsman Cancer Hospital in Salt Lake City, Utah. Today, we are going to talk about treating relapsed/refractory multiple myeloma through a case study with a high-risk patient.

Here we have a 52-year-old woman who has high-risk IgA myeloma. This was initially diagnosed back in 2015, and she had smoldering multiple myeloma at diagnosis. Her markers and symptoms were monitored closely, and then in about 2017, she presented with an increasing M spike, frequent infections, and profound immunoparesis, so the decision was made to start her on treatment at that time. She didn’t have CRAB features at diagnosis, but her monoclonal protein had been increasing. Her bone marrow biopsy showed about 20% monoclonal plasma cells, with cytogenetics that showed 1q21 gain and t(4;14), so high-risk disease. She was staged at R-ISS stage II at that time.

She started with VRd induction, had her first autologous transplant, and was in a stringent CR with MRD positivity after that. Unfortunately, she did not really tolerate maintenance therapy, so she went without maintenance and then had a progression event a few years later, in 2020. At that time, she started carfilzomib, lenalidomide, and dexamethasone and went on to a second autologous transplant. This was a decision made with her physicians and care team, based on her tolerance of treatment knowing that maintenance might again be difficult. She achieved MRD negativity after this second transplant, though still had a measurable monoclonal protein. Carfilzomib and pomalidomide consolidation was attempted, but she did not tolerate it, and then went without treatment for almost 2 years, 

She then had another progression and required her next line of therapy. At that time, she started daratumumab, pomalidomide, and dexamethasone. IMiDs have been very hard on this patient, so the pomalidomide was not tolerated. She received daratumumab monotherapy for about 6 months. At this time, she had elevated serum free light chains and was no longer making a monoclonal protein, so the kinetics of her disease had shifted. She was then collected for CAR T-cell therapy and received ciltacabtagene autoleucel in December of 2023. She achieved a stringent complete response at about 6 months from CAR-T, though unfortunately within a year had a large extramedullary progression. At that time, her disease was characterized by significant extramedullary involvement, and she was started on talquetamab. 

We’re going to talk about talquetamab post–CAR-T. It is a very good treatment choice, as it targets a different antigen than CAR-T therapies, talquetamab targets GPRC5D, which is also expressed on keratin cells, and many of the side effects are related to that expression. This patient was admitted for step-up dosing of talquetamab and had a couple of CRS events that were managed well with tocilizumab. Similar to many patients starting talquetamab, she developed oral and skin side effects quickly. For this patient, the skin side effects were more pronounced. She developed a maculopapular rash within the first cycle, which was treated with topical steroids. Unfortunately, her skin then began to blister, she continues to work and needs to be on her feet, so this was quite symptomatic, with blisters developing on her feet. 

Importantly, her light chains responded very nicely, and a short-interval PET/CT after about 2 cycles showed a dramatic response. This is encouraging, as patients who respond early to talquetamab are more likely to maintain responses. Of course, in a high-risk patient, we remain concerned about durability of response in later lines, though this patient has done well so far. 

Our clinical question is: A 52-year-old with high-risk IgA multiple myeloma started talquetamab following progression after CAR-T and quickly developed a grade 2 rash with blisters involving her feet. What would be the preferred management approach? 

• Continue talquetamab at the current dose with supportive care, such as topical steroids, emollients, and wound care.
• Hold talquetamab and start systemic steroids, then resume once improved. 
• Hold talquetamab, initiate supportive care, and consider switching to another bispecific if the rash recurs.
• Permanently discontinue talquetamab and move to another therapy.

The best answer is A: continue talquetamab at the current dose with supportive care. With bispecifics such as talquetamab, dose reductions are not recommended, but dose holds are. For grade 3 adverse events, you would hold until improvement to grade 1. In this case, the rash was grade 2, despite being symptomatic, and it was early in treatment. Given her high-risk disease and patient preference after discussion, continuing therapy with strong supportive care was appropriate. We also know that as patients respond and remain on therapy longer, dose holds and delays can help improve tolerability and reduce adverse events.

Thank you for listening and participating in this case study. We’ve learned that talquetamab, a GPRC5D-directed bispecific antibody, is an excellent option for patients who progress after CAR-T therapy. Management of adverse events can be more complex than what we are traditionally used to in multiple myeloma, particularly due to effects on keratin-expressing tissues, leading to skin, hair, and nail toxicities. Despite these symptoms, patients can do very well on this therapy, and strong supportive care and close clinical assessment are critical.