As ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma) push into earlier lines of relapsed/refractory multiple myeloma, central questions have shifted from whether CAR T-cell therapy works to when the therapy should be implanted and why so few eligible patients receive it.
“The number of people that actually get CAR T at first relapse is low but rising,” Joshua Richter, MD, an associate professor of medicine in the Division of Hematology and Medical Oncology at the Tisch Cancer Institute and director of Multiple Myeloma at the Blavatnik Family-Chelsea Medical Center at Mount Sinai in New York, New York, said during a recent OncLive® Scientific Interchange and Workshop.1
Moderated by C. Ola Landgren, MD, PhD, of the Sylvester Comprehensive Cancer Center at the University of Miami in Florida, workshop faculty traced sequencing, toxicity, and access challenges with CAR T-cell therapy in multiple myeloma and strategies to address them.
CAR T-Cell Therapy in Early Relapsed/Refractory Multiple Myeloma: Takeaways
- Many patients are eligible for CAR T-cell therapy at first relapse, yet only a small proportion receive this modality in this setting, with referral loss, patient fear, and caregiver requirements, rather than clinical contraindications, driving the shortfall.
- Sentiment has shifted toward second-line CAR T-cell therapy, partly because deeper preinfusion debulking lowers toxicity risk, and using CAR T-cell therapy first preserves a later bispecific antibody option.
- Immune effector cell–associated enterocolitis remains a poorly characterized late toxicity in need of a defined diagnostic and management pathway.
How wide Is the gap between CAR T-cell therapy eligibility and uptake at first relapse?
On April 5, 2024, the FDA approved cilta-cel for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), and who are refractory to lenalidomide (Revlimid).2 On the same day, the regulatory agency also approved a new indication for ide-cel, with the CAR T-cell therapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after 2 or more prior lines of therapy, including an IMiD, a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody.3
Updated data from the phase 3 CARTITUDE-4 trial (NCT04181827), which supported the approval of cilta-cel, showed that the CAR T-cell therapy reduced the risk of progression or death vs standard-of-care (SOC) combination regimens in patients with lenalidomide-refractory disease who had received 1 to 3 prior lines of therapy (HR, 0.29; 95% CI, 0.22-0.39).4 Data showed the 30-month progression-free survival (PFS) rate was 59.4% with cilta-cel vs 25.7% with SOC. The 30-month overall survival (OS) rates were 76.4% vs 63.8%, with a median OS that was NR in both arms (HR, 0.55; 95% CI, 0.39-0.79; P = .0009).
In the phase 3 KarMMa-3 trial (NCT03651128), which supported the third-line indication for ide-cel, updated findings demonstrated the CAR T-cell therapy (n = 254) improved PFS vs standard regimens (n = 132) at 13.8 months (95% CI, 11.8-16.1) vs 4.4 months (95% CI, 3.4-5.8), respectively (HR, 0.49; 95% CI, 0.38-0.63).5 OS outcomes were comparable at 41.4 months (95% CI, 30.9-not reached [NR]) vs 37.9 months (95% CI, 23.4-NR), respectively (HR, 1.01; 95% CI, 0.73-1.40).
Despite these data, workshop faculty estimated that although approximately 60% to 80% of patients are eligible for CAR T-cell therapy at first relapse, only 10% to 30% are treated. Several faculty who once reserved CAR T-cell therapy for later lines now favor earlier use.
“The idea of being able to cycle through a bispecific [antibody] in the next line [of therapy after CAR T-cell therapy] has made it more attractive, as opposed to the reverse, where you’re less likely to be able to go to another BCMA-targeting [agent],” said Sagar Lonial, MD, FACP, FASCO, professor and chair of the Department of Hematology and Medical Oncology, the Anne and Bernard Gray Family Chair in Cancer at Emory University School of Medicine, as well as the chief medical officer at Winship Cancer Institute of Emory University in Atlanta, Georgia.1
Bispecific combination data drew skepticism, given current frontline treatment patterns in the United States. Findings from the phase 3 MajesTEC-3 trial (NCT05083169) supported the March 2026 FDA approval of teclistamab-cqyv (Tecvayli) plus daratumumab (Darzalex) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy. However, Lonial argued that “teclistamab [plus] daratumumab is [intended for] a patient population that doesn’t exist” in US practice, noting the standard frontline use of an anti-CD38 monoclonal antibody in the form of daratumumab or isatuxumab-irfc (Sarclisa).
Faculty pointed to data for teclistamab monotherapy from the phase 3 MajesTEC-9 trial (NCT05572515), which showed a PFS improvement vs investigator’s choice of therapy in patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy.6 Although teclistamab monotherapy is not yet approved by the FDA in the early-relapse setting, Lonial and colleagues pointed to this as a potentially more deployable option after CAR T-cell therapy relapse.1
How should CAR T-cell therapy–associated toxicities be managed and contextualized?
Much of the toxicity discussion centered on correcting perception surrounding CAR T-cell therapy, with Richter noting that patients may raise concerns about adverse effects (AEs) such as Parkinsonism.
“I quote people [the] CARTITUDE-4 data, where that risk [of Parkinsonism] is [less than 1%],” Rahul Banerjee, MD, FACP, said.1,4 “I've had people come to me and say, 'Oh, your colleague [referenced a] 5% Parkinsonism [rate].’ That's not true anymore.”
Banerjee is an assistant professor in the Clinical Research Division of Fred Hutchinson Cancer Center, as well as an assistant professor in the Division of Hematology and Oncology at the University of Washington in Seattle.
“Now that we know the importance of [bridging]…I actually prefer a second-line CAR [T-cell therapy] if I can, because obviously it's much easier to get [patients] deeply debulked, even minimal residual disease [MRD] negative, going into CAR T,” Banerjee added.
What barriers most limit real-world CAR T-cell therapy access?
Faculty identified referral loss and patient misconception as larger obstacles to accessing CAR T-cell therapy, rather than clinical eligibility.
Ehsan M. Malek, MD, an associate professor of oncology and director of Roswell Park Comprehensive Cancer Center as well as an associate professor of medicine at Jacobs School of Medicine and Biomedical Sciences all in Buffalo, New York, called the caregiver requirement a primary main factor limiting CAR T-cell therapy access, noting that manufacturer financial support is generally adequate.
Banerjee urged engagement with patient communities to improve access to CAR T-cell therapy, and Richter warned that as community adoption of bispecific antibody–based regimens grows, it may hamper discussions and referrals for CAR T-cell therapy.
Particularly for patients from remote areas, where referral for CAR T-cell therapy may require considerable time and travel, Banerjee argued that simply getting those patients in the door, even virtually, could help facilitate CAR T-cell therapy conversations and allow access for more patients.
“Just having that Zoom visit to [pull] them in the door has come a really long way,” Banerjee said.
What unmet needs with CAR T-cell therapy in multiple myeloma still need to be addressed?
The workshop faculty agreed that the defining variable for CAR T-cell therapy’s future is whether earlier-line bispecific antibodies are given as fixed-duration therapy, helping preserve the target for a later CAR T-cell therapy.
Furthermore, in vivo CAR T-cell therapies could also represent the next key milestone for this class of agents, which would inherently improve access to a larger population.8
References
- From evidence to practice: interpreting emerging data on CAR T to optimize safety and patient outcomes in early relapsed/refractory multiple myeloma. An OncLive Scientific Interchange and Workshop. OncLive. June 11, 2026. Accessed July 9, 2026.
- Carvykti is the first and only BCMA-targeted treatment approved by the US FDA for patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson. April 5, 2024. Accessed July 13, 2026. https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy
- US FDA approves Bristol Myers Squibb and 2seventy bio’s Abecma for triple-class exposed relapsed or refractory multiple myeloma after two prior lines of therapy. News release. Bristol Myers Squibb and 2seventy bio, Inc. April 4, 2024. Accessed July 13, 2026. https://news.bms.com/news/corporate-financial/2024/U.S.-FDA-Approves-Bristol-Myers-Squibb-and-2seventy-bios-Abecma-for-Triple-Class-Exposed-Relapsed-or-Refractory-Multiple-Myeloma-After-Two-Prior-Lines-of-Therapy/default.aspx
- 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
- Ailawadhi S, Arnulf B, Patel K, et al. Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. Blood. 2024;144(23):2389-2401. doi:10.1182/blood.2024024582
- Mina R, Touzeau C, Hungria V, et al. MajesTEC-9: a phase 3 randomized study of teclistamab monotherapy vs investigator’s choice of pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone (PVd/Kd) in patients (pts) with relapsed refractory multiple myeloma (RRMM). J Clin Oncol. 2026;44(suppl 16):7507. doi:10.1200/JCO.2026.44.16_suppl.7507
- Sidana S, Reid B, Dima D, et al. Enhancing the safety of ciltacabtagene autoleucel in relapsed multiple myeloma (MM): Identification of potentially modifiable risk-factors associated with delayed neurotoxicity and non-relapse mortality. Blood. 2025;146(sippl 1):1034. doi:10.1182/blood-2025-1034
- Dr Spencer on the potential role for in vivo CAR T-cell therapy in myeloma. OncLive. July 8, 2026. Accessed July 9, 2026. https://www.onclive.com/view/dr-spencer-on-the-potential-role-for-in-vivo-car-t-cell-therapy-in-myeloma
