Case 2: A 57-Year-Old With R/R MM Treated with Bispecifics and Develops Neuropathy

A panel of experts on multiple myeloma offer insights on the case of a 57-year-old with relapsed/refractory MM treated with an FcRH5 bispecific antibody who develops peripheral neuropathy.


Saad Z. Usmani, MD, MBA, FACP: We can move on to the next case. Dr Tan, would you like to present this next case for us?

Carlyn Tan, MD: Patient case 2 is a 57-year-old male with R-ISS [Revised-International Staging System] stage 2 IgG [immunoglobulin G] kappa relapsed/refractory [RR] multiple myeloma [MM]. He was treated with an FcRH5 [Fc receptor-like protein 5] bispecific antibody in clinical trial. He was initially diagnosed in May 2017 and had standard risk cytogenetics. He had had 6 prior lines of therapy, including proteasome inhibitor, immunomodulatory agent, anti-CD38 monoclonal antibody, and had 2 autologous stem cell transplants. Comorbidities of note include hypertension, coronary artery disease status post-CABG [coronary artery bypass grafting], obesity, peripheral neuropathy from prior bortezomib exposure, hyperlipidemia, and fatty liver disease. He had presented with significant back pain, chest wall pain, and right shoulder pain when he had progression of disease.

The PET [positron emission tomography]-CT, as you can see on the right, shows an anterior mediastinal mass, and he had multiple lytic bone lesions. He had a salvage autologous stem cell transplant but had progressive disease based on labs in the PET-CT after 4 months. He received palliative radiation therapy to the anterior mediastinal mass as well as the shoulder lesion due to significant pain despite opiates. The patient has a history of narcotic abuse and wanted to minimize his opiate use for pain.

He enrolled in the clinical trial for FcRH5 bispecific antibody. He tolerated the step-up dosing with grade 1 CRS [cytokine release syndrome], but subsequently developed bone pain involving the shoulder, chest wall, and back. With each treatment dose, that resolved after 24 to 48 hours with the initial cycles. During cycle 2, the patient noticed increased numbness and tingling in the feet, which did not affect his activities of daily living or his gait. He did have a history of bortezomib-induced peripheral sensory neuropathy, which had improved after bortezomib was discontinued but did not resolve completely. He then developed a burning sensation in his feet that was especially worse at night with subsequent cycles. He was initially monitored for grade 1 peripheral sensory neuropathy with a burning sensation. He started on gabapentin with some relief. His sensory neuropathy did not affect his ADLs [activities of daily living]. His neuropathy remained stable, and as of late, was on a very good partial response on the clinical trial.

Saad Z. Usmani, MD, MBA, FACP: This is a very unique adverse effect. When the early reports started to come out with FcRH5 as a target and this neuropathy, it was kind of reminiscent of the bortezomib or even the thalidomide days of treating patients, but the mechanism of action for the neuropathy being induced in those patients was a bit different. Here you have a bispecific antibody that’s probably causing this through the FcRH5 expression on the peripheral nerves. Dr Tan, was this something that was expected with the FcRH5 bispecific antibody? What are your thoughts?

Carlyn Tan, MD: To be honest, I wasn’t expecting it with a bispecific antibody, but I think with more data being put out there, it is being seen and reported not just for FcRH5 bispecific antibodies but other BCMA [B-cell maturation antigen] bispecific antibodies as well. It was relatively mild, and the patient felt that it was tolerable, so he was able to continue on the clinical trial.

Saad Z. Usmani, MD, MBA, FACP: It appears that, at least from the word of mouth with investigators on these trials, there are patients who might have a propensity for this kind of neuropathy with preexisting neuropathy from other drugs in the past. Dr Scordo, what are your thoughts even with the use of second-generation IMiDS [immunomodulatory imide drugs] in someone who has had prior bortezomib-induced neuropathy? You do see some worsening in certain patients.

Michael Scordo, MD: Absolutely. We’re taking a population of patients who already have some vulnerability for this type of adverse effect, given their prior history and multiple agents in the past that can induce neuropathy. And sometimes that neuropathy is kind of getting better over time, but then they’re exposed to these newer agents where you can actually see a recrudescence of the neuropathy, or worsening. Again, I think probably a lot of the same techniques we use to treat neuropathy and the sort of pre-bispecific treatment time frame will be useful. And then, as we’ll probably discuss over the course of the next couple of cases, this idea of potentially increasing the time between doses of these agents is something that will be of interest. The other thing is there are obviously combination studies coming in the pipelines with these agents, and we might see even an increased risk of these types of adverse effects when you combine, for example, a bispecific with something like an IMiD, etc.

Transcript edited for clarity.

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