Reflecting on CAR T for First Relapse in Multiple Myeloma

As chimeric antigen receptor (CAR) T-cell therapy becomes increasingly accessible, awareness among both community oncologists and patients is shaping the course of referral to academic centers for the logistically challenging process. During a live event, Syed Abbas Ali, MBBS, associate professor of oncology at Johns Hopkins Medicine, and participants explored the growing evidence base for CAR T-cell therapy in early relapsed/refractory multiple myeloma and the persistent logistical and attitudinal barriers preventing community oncologists from referring patients sooner.

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CASE SUMMARY

• A 60-year-old man who was diagnosed 2 years ago with IgG-kappa multiple myeloma presents to his oncologist at first relapse.
• Medical history: hypertension controlled with lisinopril
• Patient received previous treatments with: D-VRd (daratumumab [Darzalex], bortezomib [Velcade], lenalidomide [Revlimid], and dexamethasone) followed by autologous stem cell transplant (ASCT) with lenalidomide maintenance
• Achieved very good partial response (VGPR) post ASCT
• Seventeen months following ASCT, the patient is now progressing and complains of excessive fatigue and low back pain exacerbated by movement.
• Now weighs 170 pounds (77 kg); down 15 pounds in last 4 months
• ECOG performance status: 0
• After discussion, it was decided to refer the patient for CAR T evaluation.

When Ali asked whether participants were already referring patients for early-line CAR T, every respondent indicated they do refer, though the conversation quickly revealed a wide range of thresholds, comfort levels, and practical concerns shaping those decisions.

Ali reviewed the approved CAR T landscape: ciltacabtagene autoleucel (cilta-cel; Carvykti) is FDA approved for patients at first relapse, whereas idecabtagene vicleucel (ide-cel; Abecma) carries approval after 2 or more prior lines.¹ BCMA-targeting bispecific antibodies should generally be reserved for after, not before, CAR T when both are potential options.

Long-term data from CARTITUDE-1 (NCT03548207) anchored the discussion. At a 61.3-month median follow-up reported at the 2025 ASCO Annual Meeting, roughly one-third of patients remained progression free 5 years after a single cilta-cel infusion without maintenance therapy, and median overall survival reached 60 months.² Ali described these results as unprecedented for a heavily relapsed population.

CARTITUDE-4 (NCT04181827) then addressed whether that durability holds in earlier lines. Updated data with a 33.6-month median follow-up, presented at the 2024 International Myeloma Society Annual Meeting and published in The Lancet Oncology, showed that cilta-cel produced a progression-free survival that was not reached vs 11.8 months with standard of care, an overall response rate (ORR) of 84.6% vs 67.3%, a stringent complete response rate of 73.1%, and minimal residual disease negativity at 10⁻⁵ in 85.6% of intent-to-treat patients vs 18.6% with standard of care (OR, 7.6).³ Among functionally high-risk patients with 1 prior line, the ORR was 100% and the complete response or better rate was 77.1%.⁴ The benefit was consistent across every subgroup examined: cytogenetic risk, ISS stage, tumor burden, and number of prior lines.

Ali tempered his enthusiasm with a candid acknowledgment that treatment-related mortality is not negligible. At high-volume academic centers, early mortality approaches 1%, but across broader practice the figure runs closer to 5% to 10%, and he has had patients die from CAR T complications at first relapse even as mortality is becoming rarer in early myeloma treatment. “Even if we are still learning about it, our patients are already aware; this needs to be part of the conversation.” He also noted a limitation of CARTITUDE-4: standard of care did not include carfilzomib (Kyprolis)-based regimens, which he would have preferred tested head-to-head.

All 11 participants voted to refer the 60-year-old directly for CAR T. The discussion then surfaced the nuanced picture of who actually makes it to infusion. Jackson Gao, MD, of Cancer Care Associates of York, described referring patients aged 80 or older for first-relapse evaluation and leaving eligibility determinations to the academic center. Grigori Okoev, MD, of Cancer Care Associates of York, agreed that fitness, motivation, access, and caregiver support are barriers, but sending patients for evaluation should be done without hesitation as it can also connect patients to the academic center for clinical trials and bispecific therapies.

Distance and accessibility of urban academic centers in Baltimore and Philadelphia were recurring barriers for patients in rural areas. Okoev noted that some older patients are more willing to travel for care than others, and Haiyun Wang, MD, Cancer Care Associates of York, described patients with Medicare who returned from Johns Hopkins Medicine, citing high out-of-pocket costs. Ali pointed to manufacturer financial assistance programs as underutilized tools of which patients should be aware. Natalia Melnyk, MD, of Upper Chesapeake Health, raised waiting times and bridging therapy as an unexpected barrier, as patients who respond well sometimes use that response as a reason to defer CAR T. Ali responded that reducing disease burden before collection is known to improve outcomes, so patients should not use this as a reason to delay infusion.

After the full data review, 70% of participants said they were very likely to refer for cilta-cel at first relapse, and 20% said likely. Ali closed by encouraging the group to send patients for evaluation even when the outcome of that evaluation is uncertain, arguing that an early consult preserves options and, critically, keeps the manufacturing clock from running behind the disease.

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_{DISCLOSURES: There were no known relevant disclosures.}

REFERENCES

1. Costa LJ, Banerjee R, Mian H, et al. International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma. Leukemia. 2025;39(3):543-554. doi:10.1038/s41375-024-02482-6

2. Jagannath S, Martin TG, Lin Y, et al. Long-Term (≥5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma. J Clin Oncol. 2025;43(25):2766-2771. doi:10.1200/JCO-25-00760

3. 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

4. Weisel K, Costa LJ, van de Donk N, et al. Ciltacabtagene autoleucel vs standard of care in patients with functional high-risk multiple myeloma: CARTITUDE-4 subgroup analysis. Presented at: EHA Congress; June 13-16, 2024; Madrid, Spain. Abstract P959.