Case 1: A 61-Year-Old with R/R MM Treated with Bispecifics and Develops Dysgeusia

Experts on multiple myeloma present the case of a 61-year-old with relapsed/refractory multiple myeloma (MM) treated with a BCMA bispecific antibody who develops dysgeusia and offer their initial impressions.


Saad Z. Usmani, MD, MBA, FACP: Hello, and thank you for joining this Cancer Network® Training Academy session titled “Monitoring and Managing Dysgeusia, Neuropathy, and Other Toxicities with Bispecific Antibodies in Multiple Myeloma [MM].” I’m Saad Usmani, the chief of the myeloma service at Memorial Sloan Kettering Cancer Center in New York. I am joined today by a health care team from Memorial Sloan Kettering involved in the management of patients with MM. I would like to welcome my fellow panelists to introduce themselves, starting with Dr Carlyn Tan.

Carlyn Tan, MD: Hi. My name is Carlyn Tan. I’m an assistant attending at Memorial Sloan Kettering Cancer Center in the myeloma service.

Michael Scordo, MD: My name is Michael Scordo. I’m an assistant attending [in] the adult bone marrow transplant service and cell therapy service at Memorial Sloan Kettering Cancer Center.

Anna Howard, RN: I’m Anna Howard. I’m a registered nurse at Memorial Sloan Kettering Cancer Center, and I work in the outpatient setting with the myeloma department.

Saad Z. Usmani, MD, MBA, FACP: Thank you for joining me. In today’s program, we are going to discuss toxicities other than CRS [cytokine release syndrome] and ICANS [immune effector cell-associated neurotoxicity syndrome] that are seen in patients with MM being treated with bispecific antibodies. We will review patient cases to illustrate how to monitor and manage these adverse events [AEs] in clinical practice. Let’s begin with our first case. Carlyn, you’re going to be talking about this case.

Carlyn Tan, MD: The first patient case is MM. She is a 61-year-old female with R-ISS [Revised-International Staging System] stage 2. IgG [immunoglobulin G] kappa relapsed/refractory [RR] MM. She has gained 1q on cytogenetic risk. She was started on a BCMA [B-cell maturation antigen] bispecific antibody for treatment after she had had 5 prior lines of therapy, including a proteasome inhibitor, immunomodulatory agents, anti-CD38 monoclonal antibody, a SLAMF7 [signaling lymphocytic activation molecule family member 7] monoclonal antibody, and cyclophosphamide. She had elected to defer an autologous stem cell transplant. Some of her comorbidities include being on a home oxygen supplementation for COPD [chronic obstructive pulmonary disease] and pulmonary hypertension, hypertension, and obesity. At the start of treatment with her BCMA bispecific antibody, her BMI [body mass index] was 34.

She enrolled in the clinical trial for the BCMA bispecific antibody. She tolerated step-up dosing with grade 1 CRS, managed with Tylenol during cycle 2. However, she started to note mild nausea, decreased appetite, as well as taste alteration. She was responding well to BCMA bispecific antibody and was in an MRD [minimal residual disease]-negative CR [complete response] after a few cycles of therapy. Her adverse events, however, continued to develop with worsening nausea, which now included vomiting as well, dyspepsia, and anorexia. Her symptoms worsened, leading to an approximately 20% decrease in body weight.

After about 5 months of therapy, she was referred to gastroenterology, and they had tentatively planned for an endoscopy for further evaluation, but there was concern regarding her respiratory status and the risks of undergoing an EGD [esophagogastroduodenoscopy]. They did a CT enterography, which was unmarkable, and she was started on omeprazole 40 mg daily and then increased to BID [twice a day]. As for her management, she was treated with nystatin for presumed oral thrush, which resolved without, unfortunately, significant improvement in her dysgeusia and her nausea. She tried multiple antiemetic agents without significant relief, including ondansetron [Zofran], prochlorperazine [Compro], lorazepam, and metoclopramide [Reglan]. She also tried dronabinol, which initially helped with her dysgeusia and appetite, but this only lasted a few weeks without significant improvement in her weight. She also started sucralfate.

Eventually, her BCMA bispecific antibody was dose reduced and transitioned to every other week dosing. Since the reduction in the dose, as well as the change in the dosing schedule, her dysgeusia, nausea, vomiting, and anorexia improved. Her weight initially stabilized, and now she started to gain back weight. Her lowest BMI during treatment was 24, and now it’s increased to 31. She has remained on treatment for about 18 months and has an MRD-negative CR.

Saad Z. Usmani, MD, MBA, FACP: Thank you, Dr Tan, for sharing this case. This is a little atypical for a BCMA bispecific as an AE. We’ve looked at data from many different BCMA constructs that have been reported in the public domain, including the FDA-approved teclistamab, [a] BCMA bispecific. So it’s something that was reported, I guess, more so with the GPRC5D [G protein-coupled receptor class C group5 member D] bispecific antibodies. Dr Scordo, what are your thoughts about the incidence of these kinds of GI [gastrointestinal] adverse effects with either BCMA or GPRC5D-directed treatments?

Michael Scordo, MD: Thanks, Saad. I agree with you. For the most part, we’ve been learning about these types of AEs and patients getting GPRC5D CAR [chimeric antigen receptor] T-cell [therapy]. The thought behind that is that GPRC5D, the target for the bispecific antibodies, is also expressed on eccrine glands and hair follicles, etc. So there may be what we call an on-target, off-tumor effect of that class of drugs, which may lead to dysgeusia.

Dysgeusia is obviously a very common occurrence in patients getting more conventional chemotherapy drugs. We see this, for example, in patients getting high-dose melphalan for a stem cell transplant. But this was a very unique toxicity that I’m not sure everyone was expecting with the bispecific antibodies. Certainly, the incidence is quite high. In fact, most of the studies will report this in the main paper. I think we’re still trying to wrap our heads around what the management really should be. Obviously, a lot of it ends up being supportive management and indirect supportive management. I think we’ll probably need to study this more over the next few years to understand if there’s a way to use a more targeted approach to combating dysgeusia, which in this case, was at least in part leading to significant weight loss and anorexia.

Saad Z. Usmani, MD, MBA, FACP: I agree. I think there have been speculations about whether this has to do with the low-grade BCMA expression. That can happen in the GI tract vs more central because we do know that BCMA is expressed in certain parts of the brain. Certainly, it’s more cerebellar, I guess, in nature. So that may be the cause.

Transcript edited for clarity.

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