Earlier Line Therapy With Cilta-Cel To Treat Relapsed/Refractory Multiple Myeloma

Evolving Treatment of Relapsed/Refractory Multiple Myeloma

In this interview, Hamza Hashmi, MD, and Maximilian Merz, MD, both of Memorial Sloan Kettering Cancer Center, examine the evolving treatment landscape of multiple myeloma. They focus on the use of Ciltacabtagene autoleucel (cilta-cel) in earlier lines of therapy, the criticality of bridging therapy, and the short-term and long-term toxicities that patients and physicians should anticipate.

Implications of CARTITUDE-4

Initially, cilta-cel was approved after three lines of therapy for the treatment of relapsed or refractory multiple myeloma, according to Dr. Merz. However, based on findings from CARTITUDE-4, an open-label, randomized, phase 3 trial, it was approved by the FDA for earlier lines of therapy, which has “changed the way we use cilta-cel in clinical practice,” he said.

The most effective strategy, Dr. Merz noted, is to begin treatment right away, sending T-cells to the manufacturer, which then produces CAR T-cells. “We try to use them right away to get this very effective treatment to the patient.”

Eligibility criteria for CAR T-cell therapy

One of the challenges for physicians, Dr. Merz noted, is identifying patients who are candidates for CAR T-cell therapy — a process that changed following the CARTITUDE-4 trial. In the past, “a lot of us confused transplant eligibility with CAR-T eligibility,” when in fact, the two are distinct, Dr. Merz said. “Any time you think about applying a next line of treatment to your patient, he or she should definitely be evaluated for CAR-T therapy, because there are only mild contraindications.”

For those who do meet the criteria, he advised starting as soon as possible. “Every time you recognize that the monoclonal protein (M spike) level is crawling up and there are signs for serological progressive disease, even at the frontline setting, your patient should be evaluated for CAR-T therapy,” Dr. Merz said. “The earlier, the better.”

Cilta-cel and bridging therapy

According to data from CARTITUDE-4, cilta-cel can play a critical role in bridging therapy. When used in earlier lines of treatment, it can reduce the tumor burden prior to infusion, which can “pave the way for longer, progression-free survival — and in some patients, long-term survival without any disease” — while also helping to reduce side effects, said Dr. Merz. 

Ensuring patients continue bridging therapy from T-cell collection to actual infusion is vital, Dr. Merz said, along with checking for remission prior to starting infusion therapy. “If the patient develops a problem during bridging, like rapidly progressive disease, then we have to change plans,” he said. “It’s never a good idea to use CAR-T in a patient who’s actively progressing.”

Hematotoxicity

Another important component is educating both physicians and patients on which toxicities are likely to occur after discharge from CAR T-cell therapy. The most prevalent is hematotoxicity, which can result in low white blood cell counts. In rare instances, patients may present with neurotoxicities, including parkinsonism, or colitis, both of which should be reported as soon as possible. “We try to brief our patients and caregivers in great detail,” Dr. Merz said.

Collaboration, Dr. Hashmi added, is a critical aspect in providing care for patients with multiple myeloma, and will continue to be the case. “It’s a team effort between the referring providers, the CAR-T physicians, and multiple other sub-specialties.”