Pharmacists Play an Essential Role in Bispecific Therapy for Multiple Myeloma

Pharmacists play a crucial and varied role in the administration of bispecific medications, particularly in the treatment of multiple myeloma (MM), according to the moderator of a Pharmacy Times^® Clinical Forum discussion held in Detroit, Michigan.

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MM remains incurable, although progress is being made towards a cure. Individuals who have failed triple or quadruple classes of drugs face a poor survival rate of less than 1 year.

The moderator, Brooke Adams, PharmD, BCOP, a clinical pharmacy specialist in blood and marrow transplantation and cellular therapy at Orlando Health and a clinical assistant professor at the University of Florida College of Pharmacy, explained that since 2020, there has been an increase in new therapies, but it is unclear how to sequence them. Chimeric antigen receptor (CAR) T-cell therapy, which is often used for MM treatment, is effective but has limitations, including a manufacturing time of up to 6 weeks. After several lines of therapy, T cells may become exhausted, which could limit the effectiveness of CAR T-cell therapy in later lines of treatment. Bispecifics are an off-the-shelf option that work by engaging T cells to bind to CD3 on the cells.

Currently, bispecifics are approved by the FDA for use after 4 prior lines of therapy that must have included an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory drug (IMiD).

The responsibilities of pharmacists begin once a provider decides that a patient will start bispecific therapy. These include determining the logistics of administering the medications and playing a central role in Risk Evaluation and Mitigation Strategy (REMS) programs, which are specific to myeloma bispecifics, the panelists noted. REMS programs are designed to monitor and mitigate the potential risks associated with these powerful drugs.

“The multiple myeloma bispecifics have the luxury of a REMS program, where every other bispecific doesn't. Then we have step-up dosing to try to mitigate these side effects, pre-medications, and then recommended in-patient observation,” Adams said.

The Clinical Forum participants also discussed individual bispecific therapies, including talquetamab-tgvs (Talvey; Janssen Pharmaceutical), highlighted for its unique target, the G protein-coupled receptor, class C, group 5, member D (GPRC5D). The panelists noted that pharmacists are observing a trend toward weekly administration of talquetamab in some institutions, although not all pharmacists agree with this shift.

“These agents don't work as quickly as your traditional agents, so I think that there is still a huge unmet need because you can't just start these agents, and patients acutely need to be treated. You have to bridge as you would with CAR T-cell therapy—and I think that is a reason why this patient population is still an unmet need with this line of therapies,” Izabela Mazur, PharmD, BCOP, a hematology oncology specialist at Henry Ford Health System, explained.

Talquetamab is administered weekly or biweekly, though there is a debate about the potential impact of weekly dosing on adverse effects, with some providers suggesting that it may increase toxicity. In addition to this, talquetamab is noted to have a distinct adverse effect profile, including taste disturbances, dry skin, and weight loss.

“We don't know how to treat them. We don't know if they're dose-related; we don't know if they're peak- or trough-related; we know nothing. Over time, people get their taste back by doing nothing, but we will absolutely get there,” Adams said.

The panelists also discussed the sequencing of bispecific therapies in relation to other treatments, like CAR T-cell therapy. As an example, a panelist shared that there is a preference for using bispecific antibodies that target B-cell maturation antigen (BCMA) before GPRC5D, unless the patient has received prior BCMA-targeted CAR T-cell therapy.

In cases where patients have received prior BCMA-targeted CAR T-cell therapy, providers are often preferring talquetamab first, according to the panelists. The decision-making process for treatment options is complex and individualized, with pharmacists often involved in presenting advantages and disadvantages of each treatment to providers and patients.

“What I started doing is sitting down with the provider and the patient, and we make a pro and con list on our whiteboard for the patient. Because, ultimately, it's their decision. It's their therapy, it's their treatment, it's their money, it's their myeloma—who are we coming in to tell you what's right?” Adams said.

Pharmacists play an indispensable role in the evolving landscape of MM treatment, particularly with the advent of bispecific therapies. The panelists emphasized that pharmacists are not merely dispensers of medication; they are active participants in the multidisciplinary care team, and their knowledge is crucial in determining the administration of bispecifics. This is demonstrated as they navigate the REMS programs and monitor and manage adverse effect profiles associated with these drugs, such as talquetamab.

“As pharmacists, we're the ones that figure it out and do all of the work to get it to our patients,” Adams said.

As treatment paradigms shift and new agents become available, pharmacists serve as essential resources for healthcare providers, contributing to informed decision-making and ultimately optimizing patient outcomes and safety in the use of bispecific antibodies.