Insurance Delays and Travel Strain CAR T Referral in Early Relapsed Myeloma

For patients with relapsed/refractory multiple myeloma (RRMM) who are candidates for chimeric antigen receptor (CAR) T-cell therapy, treatment decisions must be made carefully before cells are collected. Myeloma must be controlled through the course of apheresis and manufacturing without harming the T cells that will be used, and insurance approval, travel, and caregiver support can delay the whole sequence. Choosing a holding or bridging regimen therefore depends on disease burden, the target of the CAR T product, and whether the patient can reach a treatment center.

In a live Case-Based Roundtable event in Houston, Texas, Robert Orlowski, MD, PhD, professor of medicine in the Departments of Lymphoma/Myeloma and experimental therapeutics in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, reviewed CAR T and bridging data for RRMM and moderated discussion of a 72-year-old man with an aggressive first relapse who lives an hour from an academic center. Orlowski emphasized that he favors CAR T-cell therapy at second line for patients with molecularly high-risk disease or aggressive relapse but does not make it the default for all second-line patients.

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This article is part 1 of a 2-part series from a Case-Based Roundtable event.

CASE SUMMARY

• A 72-year-old man with newly relapsed multiple myeloma presents to the clinic to discuss his next treatment options.
• ECOG performance status, 1; International Staging System (ISS) I/Revised ISS I; standard cytogenetic risk
• He typically prefers to minimize time spent in the hospital and has an hour-long commute to the academic center.
• He understands that CAR T requires treatment at a specialized facility and is willing to proceed with CAR T given his aggressive relapse.

Treatment History

• March 2019: daratumumab (Darzalex), bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Dara-VRd); complete response (CR)
• August 2019: autologous stem cell transplant (ASCT) followed by lenalidomide maintenance
• October 2023: Relapse

EVENT RECAP

Asked how they would treat the patient at first relapse, 45.5% of 11 respondents chose referral for CAR T, 27.3% an anti-CD38–based regimen, 18.2% daratumumab plus teclistamab (Tecvayli), and 9.1% a selinexor (Xpovio)-based regimen.

Orlowski reviewed NCCN listings that include bispecific antibody regimens, ciltacabtagene autoleucel (cilta-cel; Carvykti), and selinexor-based combinations.¹ The International Myeloma Working Group recommendation is to use CAR T-cell therapy before a T-cell engager when a patient is a candidate for both, and a T-cell engager first when rapidly progressing disease makes completing apheresis and bridging unlikely.² Natalie Rafaeli, MD, of the University of Texas in Houston, asked about a non–B-cell maturation antigen (BCMA) T-cell engager first. Orlowski responded that talquetamab (Talvey) is technically approved only at the fifth line or later, though a lower infection risk made it worth considering, at the cost of skin, nail, and taste toxicity.

Orlowski discussed the phase 3 CARTITUDE-4 trial (NCT04181827), which randomly assigned patients with 1 to 3 prior lines of therapy and lenalidomide-refractory disease to cilta-cel or standard-of-care triplets. At a median follow-up of 33.6 months, median progression-free survival (PFS) was not reached with cilta-cel vs 11.8 months with standard of care (HR, 0.29; 95% CI, 0.22-0.39), and overall survival (OS) was associated with a lower risk of death (HR, 0.55; 95% CI, 0.39-0.79; P = .0009).³ In the phase 3 KarMMa-3 trial (NCT03651128), which enrolled patients with 2 to 4 prior lines, median PFS with idecabtagene vicleucel (ide-cel; Abecma) was 13.8 months vs 4.4 months with standard regimens (HR, 0.49; 95% CI, 0.38-0.63) at a median follow-up of 30.9 months. Median OS was 41.4 months vs 37.9 months, which did not differ significantly (HR, 1.01; 95% CI, 0.73-1.40).⁴ This study did allow crossover to CAR T, and Orlowski noted that the OS data were immature. The trials enrolled different populations, so their results cannot be compared directly.

When the question of CAR T access was raised, 45.5% of the participants called insurance delays the greatest challenge to CAR T access, 36.4% logistics and caregiver support, and 18.2% patient eligibility. Tri Vu, MD, named insurance first. Anirudha Dasgupta, MD, of Texas Oncology in The Woodlands, Texas, described a patient with primary refractory disease whose insurer refused both ASCT and cellular therapy. Orlowski described a patient who was denied CAR T for lack of a prior ASCT, even though the FDA approval of CAR T does not require prior ASCT.

Bachar Samra, MD, of Kelsey-Seybold Clinic in Spring, Texas, said he explains the basics of cell therapy, including neurotoxicity and the need for a caregiver: "I don't overwhelm them because I don't want to scare them." Asked what proportion of referred patients complete infusion, 4 of 11 respondents estimated half, 3 estimated three-quarters, 3 estimated nearly all, and 1 estimated one quarter. Participants cited patient decision, difficulty navigating 2 health systems, clinical decline, and disease that did not respond to bridging.

When discussing bridging to CAR T, Orlowski specifically defined holding therapy as treatment before apheresis and bridging as treatment after collection while manufacturing continues.² He advised a washout of at least 2 weeks, the minimum regimen that controls disease, and avoiding bendamustine and, when possible, the same target as the CAR T product.⁵

In a retrospective analysis of 45 patients with heavily pretreated disease, prior selinexor exposure did not appear to compromise outcomes of BCMA-directed CAR T-cell therapy (response rate to CAR T, 89%; median follow-up, 68 months).⁶ In a multicenter retrospective analysis of 134 patients who received talquetamab as a bridge, 119 (89%) proceeded to CAR T; 71% responded to talquetamab and 88% responded after CAR T (complete response, 54%).⁷

Participants differed on when to bridge. "I try not to bridge if it's possible," Rafaeli said, aiming for low disease burden at infusion. Vu said he uses a variation of the holding regimen. Mohsen Arani, MD, of Texas Oncology in The Woodlands, Texas, said symptomatic bone disease, kidney dysfunction, and a short response to prior therapy would push toward aggressive bridging. For this patient, 36.4% of 11 respondents chose an immunomodulatory drug with or without an anti-CD38 antibody, 27.3% selinexor, 27.3% talquetamab, and 9.1% other. For a patient with heavily pretreated disease, 54.5% chose talquetamab and 36.4% selinexor.

For third line after relapse on cilta-cel, 63.6% of 11 respondents chose a talquetamab-based regimen. Tejo N. Musunuru, MD, of MD Anderson in League City, Texas, said the choice is "whatever they haven't seen before, and the insurance approves at that point." Dasgupta said a long third-line discussion can confuse patients and families and backfire on the physician, so the options are sorted and offered as one choice. One oncologist said practice pathways leave little room to choose. Orlowski said that if selinexor had been the bridge and produced a response, reusing it could be reasonable.

Participants treated insurance approval and travel as the main limits on CAR T-cell therapy, and they chose bridging by disease tempo and prior drug exposure rather than by a single standard. Orlowski stressed the CAR T conversation belongs at second line, though some patients will choose to wait.

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_{DISCLOSURES: Orlowski previously reported equity interest in Asylia Therapeutics; consulting fees from Amgen, Bristol Myers Squibb, Celgene, EcoR1 Capital, Forma Therapeutics, Genzyme, GlaxoSmithKline, Ionis Pharmaceuticals, Janssen, Juno Therapeutics, Kite Pharma, Legend Biotech, Molecular Partners, Sanofi, Servier, and Takeda; and research funding from Asylia Therapeutics, BioTheryX, Heidelberg Pharma AG, and Genentech.}

REFERENCES

1. NCCN. Clinical Practice Guidelines in Oncology. Multiple Myeloma, version 1.2027. Accessed September 15, 2026. https://tinyurl.com/37vy9pm2

2. 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

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. 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

5. Ailawadhi S, Anderson LD Jr, Dhakal B, Shune L, Sborov DW, Hansen DK. Optimizing selection of bridging therapies prior to CAR-T therapy administration for multiple myeloma: clinical pearls from an expert roundtable. Clin Lymphoma Myeloma Leuk. 2026;26(2):85-93. doi:10.1016/j.clml.2025.08.005

6. Costa BA, Dima D, Mark T, et al. Impact of prior selinexor exposure on outcomes of chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma: an exploratory analysis. J Clin Med. 2025;14(4):1316. doi:10.3390/jcm14041316

7. Dhakal B, Akhtar OS, Fandrei D, et al. Sequential targeting in multiple myeloma: talquetamab, a GPRC5D bispecific antibody, as a bridge to BCMA CAR-T cell therapy. Blood. 2025;146(17):2063-2072. doi:10.1182/blood.2025029773