Cell Therapy / Resource Centers 08/18/2026

CAR-T First Emerges as Recommended Therapy For Relapsed/Refractory Multiple Myeloma

A bald man wearing a pink sweater and blue checkered bow tie, standing outdoors with blurred background in natural light. Hamza Hashmi, MD Professional man in a blue suit and glasses smiling in an office setting. Maximilian Merz, MD

Key Points

  • Although CAR T cell therapy and bispecific antibodies have been approved as early as first relapse in patients with multiple myeloma, evidence supports the use of CAR-T first.
  • Notable exceptions include elderly patients and those with major organ comorbidities, who “may be a better fit” for bispecific antibody-based therapy.
  • The CARTITUDE trials have produced valuable data in guiding the treatment of relapsed/refractory multiple myeloma; however, more information is needed regarding neurocognitive toxicities.

Sequencing BCMA-Directed Therapies in Multiple Myeloma

In this interview, Hamza Hashmi, MD, and Maximilian Merz, MD, both of Memorial Sloan Kettering Cancer Center, discussed some of the “exciting developments” that have surfaced regarding the use of B-cell maturation antigen (BCMA)-directed therapies in relapsed/refractory multiple myeloma, and explored how those findings are affecting treatment decisions.

Although Chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies have been approved for use as early as first relapse in patients with multiple myeloma, evidence still supports using CAR T-cell therapy first. However, there are notable exceptions, along with toxicities that physicians should be aware of.

CAR-T Before Bispecifics

In the multiple myeloma treatment community, there are ongoing efforts to determine the optimal course of treatment with BCMA-directed therapies in patients with relapsed or refractory multiple myeloma. As clinical trial data become available, physicians continue to question how to sequence CAR-T therapies and bispecific antibodies, since both have been approved for use as early as first relapse.

“The general pattern, based on some of the research data, consortium-based data, and guidelines-based consensus that we have, favors CAR-T before a BCMA-directed bispecific antibody rather than the reverse,” said Dr. Hashmi.

Real-world data indicate that patients tend to fare better with CAR-T first, likely because prior bispecific exposure can select for BCMA-resistant clones. Additionally, “long-term exposure with T cell engagers raises the risk for CAR-T manufacturing failure,” Dr. Hashmi said. Therefore, if sequential BCMA exposure is unavoidable, he recommended at least a three-month—if not a six-month—washout period between two BCMA-directed treatment options, including CAR-T and bispecifics.

If a patient has had a prior BCMA-directed bispecific antibody and it is difficult to avoid a washout, Dr. Hashmi’s preference is to use a non-BCMA target, such as GPRC5D-directed Talquetamab, for patients who are relapsing more quickly. Importantly, “a lot of the risk factors that we took into consideration previously have been mitigated by the availability of these options at first relapse,” Dr. Hashmi stated.

Notable Exceptions

There are, however, notable exceptions to the sequencing, including advanced age (80 years or older), compromised performance status, major organ comorbidities, oxygen-dependent COPD, advanced stage symptomatic heart failure, renal failure, and dialysis. Patients who fall into those groups, according to Dr. Hashmi, “may be a better fit” for bispecific antibody-based therapy.

Similarly, patients who don’t have a full-time caregiver or don’t reside near a major academic center may want to consider bispecifics, provided they are “understanding and are accepting of some of the risks associated with long-term use,” Dr. Hashmi said.

Neurocognitive Toxicities

Dr. Hashmi highlighted a critical learning that has emerged in the CARTITUDE trials around the movement of neurocognitive toxicities. “As we moved from late-line relapses to early-line relapse, we realized there are a bundle of strategies, including better bridging options, to lower the tumor burden through aggressive early management of CRS and ICANS with tocilizumab and corticosteroids,” he said. Careful handwriting monitoring and screening at least twice a day for all patients during the first 14 days are highly recommended, with extended monitoring in some cases.

Where the CARTITUDE program falls short, Dr. Hashmi noted, is in producing data around some of the rare, delayed-onset non-ICAN neurological toxicities, particularly the parkinsonism profile. “I still find it’s a little harder to predict and doesn’t always reliably respond to prophylactic corticosteroids.”

In fact, “a lot of the management strategies that we have employed do not reliably work in all of our patients whether it is in the form of steroids, IVIG (Intravenous Immunoglobulin), or parkinsonism drugs,” Dr. Hashmi said. He emphasized the need for “long-term surveillance vigilance and a very low threshold for neurology evaluation, even a year beyond infusion to effectively identify and mitigate manage some of these complications.”

Continued Evolution

Both Drs. Hashmi and Merz expect that the treatment landscape for BCMA target therapies will continue to evolve in the next few years. Based on preliminary data, “we’re seeing some very deep and durable MRE-negative responses with single-time infusion of cilta-cel without requiring any further ongoing therapy,” said Dr. Hashmi, who anticipates that CAR-T will obtain additional approvals in earlier lines of therapy.

An area they will continue to monitor is off-the-shelf allogeneic CAR-T, which could offer a solid option, but is associated with an increased risk of infection. “The field has more powerful tools today than it has clear rules to how to use some of these tools,” Dr. Hashmi said. “The next few years of real-world data and clinical trials are going to have a significant impact on our practice.”