Dr Chari on the Selection of BCMA-Targeted Therapies Within Multiple Myeloma

Ajai Chari, MD, director, clinical research, Multiple Myeloma Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses important patient factors to consider when selecting between currently approved BCMA-targeted therapies for the treatment of patients with multiple myeloma.

Of the recent BCMA-directed therapies that have been approved in multiple myeloma treatment, many have an indication for patients who received 4 or more lines of therapy and are triple-class exposed to a proteasome inhibitor, immunomodulatory agent, and anti-CD38 therapy, Chari begins. If a patient meets those criteria, the next biggest determinant aside from insurance approval is the rate of their disease progression, he says.

The biggest differentiation between bispecific antibodies and CAR T-cell therapy is the infusion wait time for CAR T-cell therapy, Chari explains. Manufacturing CAR T-cell therapy is a lengthy procedure in which T cells are collected from the patient through apheresis. Logistical challenges associated with this process can often result in manufacturing delays, longer wait-times for patients, or a complete lack of access to this therapy, Chari details. Conversely, bispecific antibodies are off-the-shelf and are more readily available for administration, Chari adds.

Another key factor to consider is the selection bias that arises from the patient enrollment process in early-phase clinical trials, Chari continues. Historically, CAR T-cell trials involving CAR T-cell therapy were often conducted in heavily pretreated populations and had limited slots, Chari describes, leading institutions to carefully choose their patients. The resulting selection bias has influenced real-world decision-making and reflects the difficulty many patients experience when attempting to access CAR T-cell therapy, Chari says.

In order to receive CAR T-cell therapy, patients with rapidly progressing disease must remain stable for apheresis, while awaiting insurance approval, Chari states. After obtaining this approval many patients must wait several more weeks for their scheduled time slot. Patients’ stability must be maintained for a minimum of 4 to 6 weeks after apheresis, which can be a challenge, he adds. Chari also notes that some of the most recent CAR T-cell products have data that do not meet the predefined efficacy cutoffs agreed upon by health authorities. This complicates long-term follow-up data for these patients, he says.

Ultimately, patients with rapidly progressing disease may benefit more from treatment with a bispecific antibody, as this is a more immediate treatment option, Chari advises. Conversely, patients with indolent disease who are considered fit, are far from academic centers that administer ongoing bispecific therapy and can tolerate potential treatment-related neurotoxicity may be better candidates for CAR T-cell therapy, Chari concludes.