Mapping Practical Steps to Expand CAR T-Cell Access in Multiple Myeloma

With 2 CAR T-cell therapies now approved in earlier lines of relapsed multiple myeloma, the question may no longer be whether CAR T-cell therapy works. Instead, the question is how to get the right therapy to the right patients at the right time.

In a special CancerNetwork^® discussion, Joshua Richter, MD, and Marco Davila, MD, PhD, highlighted key considerations for the practical use of CAR T-cell therapies in multiple myeloma. They discussed when to refer, how to sequence CAR T-cell therapy with bispecific antibodies, how to manage toxicities across care settings, and how to reach patients who live far from a treatment center.

Richter is an associate professor of Medicine in the Division of Hematology and Medical Oncology at The Tisch Cancer Institute, as well as the director of Multiple Myeloma at the Blavatnik Family - Chelsea Medical Center at Mount Sinai. Davila is the senior vice president and associate director for Translational Research, a professor of Oncology, chief of Lymphoma/Multiple Myeloma Service, and Rustum Family Endowed Chair in Translational Research at Roswell Park Comprehensive Cancer Center.

Evaluate Every Patient Early

With ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma) both approved in earlier lines, Davila said earlier use offers more time to coordinate, better-quality T cells, lower toxicity risk, and more treatment-sensitive disease. Not every patient needs CAR T-cell therapy in the second line, but every patient should be evaluated.

“Who’s the optimal patient for referral? All of them,” Davila said. “I may not recommend cell therapy for all of them, but I want to see them all.”

Richter noted that the “rainy day” clinicians once saved therapies for often never comes. “Patients in the US only get around 3 to 4 lines of therapy,” he said.

The Case for CAR T Before Bispecifics

Because many patients will receive both a CAR T-cell therapy and a bispecific antibody, Richter called sequencing “the billion-dollar question in [multiple] myeloma.” He noted findings from the University of Pennsylvania group showing better outcomes when CAR T-cell therapy comes first, driven largely by a longer interval between BCMA-directed treatments.

“You want to give them not just the best therapy now, but [the best therapy] in the overall landscape of their journey,” Richter said.

Who is a Candidate?

The ideal candidate for CAR T-cell therapy has early relapse, low tumor burden, and few comorbidities. However, Davila stressed that older populations and those with comorbidities or higher tumor burden can still achieve durable remissions. He is more cautious with patients who have baseline neurologic conditions such as parkinsonism or seizure disorders, recurrent infections, or very limited life expectancy.

Richter acknowledged that “the average patient on a clinical trial is not the average patient that’s going to walk into your clinic,” but said that real-world data, alongside findings from the phase 3 KarMMa-3 (NCT03651128) and CARTITUDE-4 (NCT04181827) trials, show benefit for patients outside trial eligibility criteria.^1,2 “There are far fewer patients that are CAR T ineligible compared with auto transplant ineligible,” he said.

Referral as a Partnership

Davila compared the referral relationship to a marriage in which both sides have an equal say. The referring physician follows the patient across the full treatment journey while the cell therapy team includes the referrer in decisions about eligibility, holding therapy, and bridging. “There is a role incumbent on us as academic cell therapy clinicians,” he said. “How can I make it easier for referrers and patients to be able to get this therapy?”

Richter shares his cell phone number with community physicians and texts with them about new symptoms. “It’s an ongoing relationship,” he said.

Managing Toxicities After Discharge

Richter asks community physicians to call him about “anything other than the sniffles.” New diarrhea may warrant academic gastroenterology evaluation to distinguish infection from immune effector cell–associated enterocolitis, and unexplained fevers may call for testing for cytomegalovirus or Epstein-Barr virus reactivation.

Davila said consensus management has followed quickly once toxicities are named and discussed across centers, as happened with movement disorders. “Early identification [and] early intervention really does improve outcomes,” he said. Now that patients return home sooner, centers must make sure practice changes reach their community partners.

Closing Rural Access Gaps

Davila described upstate New York as a CAR T “desert,” with 2 main treatment centers serving a large rural population. Roswell Park now offers cell collection closer to home in Syracuse; is working on a site near Albany; and relies on telemedicine, local holding and bridging therapy, shared long-term surveillance, and manufacturer support programs for travel and lodging. “We don’t want them to think that the barriers that existed 5 years ago are still there today,” he said.

Richter added that care plans should fit the patient. For example, an older patient who lives far away may be safer admitted than treated as an outpatient.

Misconceptions That Delay Referral

Richter said he still hears 2 misconceptions: that transplant ineligibility means CAR T ineligibility, and that CAR T-cell therapy is reserved for triple-class refractory disease. “Age is just a number,” he said. “We all have 80-year-olds who are running marathons and 50-year-olds who come in in wheelchairs after a quadruple bypass.”

Davila said other options can simply seem easier for a busy oncologist with 10 to 15 minutes per visit. “I really think it’s just [an] incomplete understanding of where the field is today,” he said.

Key Takeaways

“Cell therapy is one of the best opportunities available for patients that put them into remission for years. That’s the goal,” Davila said, adding that his team’s role in a patient’s care “doesn’t end at day 15.”

Richter expects positive readouts from the phase 3 CARTITUDE-5 (NCT04923893) and CARTITUDE-6 (NCT05257083) trials of cilta-cel in newly diagnosed disease. “CAR T-cell therapy is now deeply entrenched in the world of relapsed multiple myeloma, soon to be likely entrenched in the newly diagnosed world,” he said. “Having that ongoing communication back and forth, especially as the field is moving so quickly, is absolutely key in providing optimal care for our patients.”

References

1. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023;388(11):1002-1014. doi:10.1056/NEJMoa2213614
2. Einsele H, San-Miguel J, Dhakal B, et al. Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): an updated analysis including overall survival from an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2026;27(2):254-268. doi:10.1016/S1470-2045(25)00653-9