‘Immunotherapy is here’ for treatment of multiple myeloma
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Novel B-cell maturation antigen-directed immunotherapies are ready to take their place as the new standard for treatment of advanced multiple myeloma, according to a panel at NCCN 2022 Annual Congress: Hematologic Malignancies.
“Immunotherapy is here for multiple myeloma,” Christopher R. D’Angelo, MD, assistant professor in the division of hematology and oncology at University of Nebraska Medical Center, told the audience.
D’Angelo joined two other multiple myeloma specialists who presented case studies and gave the audience recommendations on how to incorporate newer B-cell maturation antigen (BCMA)-directed immunotherapies — including belantamab mafodotin-blmf (Blenrep, GSK) and chimeric antigen receptor T-cell therapy — into the treatment arsenal.
The process begins with identifying who would likely benefit from treatment with immunotherapy based on patient and tumor characteristics, according to Patricia A. Mangan, RN, MSN, APRN-BC, nurse coordinator for the multiple myeloma/lymphoma and autologous stem cell transplant programs at University of Pennsylvania's Abramson Cancer Center.
Clinicians will also need to educate themselves on potential adverse events related to the use of BCMA-directed therapies, she added.
The current immunotherapy landscape for treatment of multiple myeloma also includes monoclonal antibodies and antibody-drug conjugates, with pending FDA approval of the first bispecific antibodies currently in later-stage clinical trials, Mangan noted.
Belantamab mafodotin-blmf
Belantamab mafodotin-blmf, administered as an IV infusion, is “nicely designed to be given as an outpatient regimen,” Mangan said.
With median OS not yet reached in the pivotal clinical trial leading to FDA approval, belantamab mafodotin-blmf provides durable responses and is a “nice agent to have in our therapy arsenal,” she said.
However, Mangan cautioned about adverse events related to the agent, including keratopathy and other ocular-related toxicities, which occurred in more than three-quarters of patients. Additional adverse events include hematologic toxicities, such as thrombocytopenia and anemia.
With patients facing such a high risk for keratopathy while receiving belantamab mafodotin-blmf, Mangan said she’s found it helpful to prepare them for the likelihood of this toxicity prior to therapy.
The risk for keratopathy led the FDA to include belantamab mafodotin-blmf as part of its risk evaluation and mitigation strategy (REMS) program, according to Jason Bergsbaken, PharmD, MBA, BCOP, pharmacy coordinator of regional oncology services at UW Health and University of Wisconsin Carbone Cancer Center. This will require one-time enrollment by prescribers and ongoing ocular exams of patients who receive the agent, he added.
“Work with your ophthalmology colleagues to develop a workflow for these patients before they receive therapy,” D’Angelo said. “It’s important to catch any issues early because there are dose-mitigation strategies available.”
CAR T cells
Two BCMA-directed CAR T-cell products have been approved for commercial use in the United States for patients with heavily pretreated multiple myeloma — ciltacabtagene autoleucel (Carvykti; Janssen, Legend Biotech) and idecabtagene vicleucel (Abecma; Bristol Myers Squibb, bluebird bio).
One of the largest questions related to use of these products involves whether to provide bridging therapy in the lead-up to CAR-T infusion while patients wait for manufacturing of the final product.
Emerging data suggest that bridging therapy before CAR-T lessens treatment-related toxicity by reducing tumor burden, D’Angelo said.
“There is not a one-size-fits-all solution to using bridging therapy,” he said. “Rather, you should consider what you want to achieve for the patient in each case.
D’Angelo said goals include controlling disease to limit overall toxicity and get patients through to CAR T-cell therapy, but also to hopefully maximize the effectiveness of CAR T cells after infusion.
In terms of safety, both FDA-approved CAR-Ts have low rates of treatment-related high-grade cytokine release syndrome and even lower rates of neurotoxicity, D’Angelo noted. He cautioned about limited cases of Parkinson’s-like syndrome reported in clinical trials among patients who received ciltacabtagene autoleucel.
There are numerical differences in response rates between the two therapies, but no head-to-head randomized comparisons have been conducted, D’Angelo said. Regardless of which therapy a patient receives, patients are “truly blessed” to have two such options available at this time, he added.
“For the first time, we now have a single-dose treatment with high efficacy for many of our patients with multiple myeloma,” D’Angelo said. “It offers them a break from treatment that many of them have not had in years.”
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D’Angelo CR, et al. How to incorporate immunotherapies in the management of multiple myeloma. Presented at: NCCN 2022 Annual Congress: Hematologic Malignancies; Oct. 14-15, 2022; New York.
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