Referral Before Salvage Therapy Keeps CAR T an Option in Myeloma

Chimeric antigen receptor (CAR) T-cell therapy with ciltacabtagene autoleucel (cilta-cel; Carvykti) is a preferred category 1 option for patients with multiple myeloma who have relapsed after 1 to 3 prior therapies,¹ but access depends on more than disease biology and patient fitness. Manufacturing can lead to delays in treatment, payers may question referrals made after a salvage regimen has started, and the nearest treatment center may be far from the patient’s home.

In a live Evolving Paradigms Roundtable event in Orlando, Florida, Rushang Patel, MD, PhD, director of the Malignant Hematology, Stem Cell Transplant, and Cellular Therapy programs at AdventHealth Orlando, reviewed long-term and real-world data on CAR T-cell therapy in early relapsed myeloma and moderated discussion of how community oncologists select candidates, time referrals, and manage patients after infusion. Patel emphasized that referral at the first rise in disease markers, before salvage therapy begins, can help get patients timely access.

Register today to join a Case-Based Roundtable near you.

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

DISCUSSION QUESTIONS

• How do you decide if a patient is eligible for CAR T-cell therapy?
• How early in the treatment process do you refer your patients for CAR-T?
• What supportive care guidelines would be helpful for the referring site to receive from the treatment center during patient transition post CAR-T?

EVENT RECAP

Participants were polled on the preferred early relapse option for patients refractory to anti-CD38 therapy. Of 9 respondents, 6 (66.7%) chose CAR T-cell therapy, and 1 respondent (11.1%) each chose a regimen based on teclistamab (Tecvayli), belantamab mafodotin (Blenrep) with bortezomib and dexamethasone, or conventional triplet therapy. Patel commented that “not giving [CAR T-cell therapy or a bispecific antibody] to a second line…patient is like trying to use chlorambucil for [chronic lymphocytic leukemia].”

For patients with 1 to 3 prior lines of therapy and lenalidomide-refractory disease, Patel reviewed 5-year follow-up from cohort A of the CARTITUDE-2 trial (NCT04133636), which enrolled 20 patients. At a median follow-up of 60.7 months, 50% of patients were alive and progression-free without further antimyeloma treatment 5 years or more after infusion, median progression-free survival (PFS) was 60.5 months, and the 5-year overall survival (OS) rate was 69.2%.² Median PFS and OS were numerically higher than in CARTITUDE-1 (NCT03548207), which enrolled patients with 3 or more prior lines, but the cohorts differ in size and population, so the results cannot be compared directly.² Patel attributed the benefit of earlier use to the fitness of a patient’s own T cells, which Patel said declines with each line of therapy.

A retrospective multicenter analysis of 640 patients compared starting with CAR T-cell therapy vs a bispecific antibody. Starting with CAR T-cell therapy was associated with longer remission and higher OS, and the risk of death after progression did not differ significantly by initial treatment; the authors called the findings exploratory.³ Patel cautioned that the data were not randomized and said that about 80% of patients who started with a bispecific antibody did so because they could not reach a CAR T center, whether from insurance, distance, or health.

On selection, one participant said that patients who are much older, with multiple comorbidities and limited family support, are an easy call to exclude. Asad Sheikh, MD, of Orlando Health Cancer Institute in Sanford, Florida, added that distance from a small-town practice to the treatment center is a major barrier. Patel said CAR T eligibility is more lenient than for autologous stem cell transplant, which Patel personally stops offering at age 75, and that the program has treated patients in their 80s. Sreeram Maddipatla, MD, of Orlando Health in Orlando, Florida, described leaning toward CAR T because the alternatives are “going to be [given for] a lifetime…we have to keep giving the treatments.”

Sheikh noted that CAR T-cell therapy requires time for manufacturing, whereas bispecific antibodies are available off the shelf. Patel said that the approval of bispecifics in the second line has eased that dilemma, and now the CAR T program can use a bispecific antibody as salvage and bridging while cells are manufactured. As a clinical call rather than a rule, Patel avoids a bispecific antibody that targets B-cell maturation antigen (BCMA) before BCMA-directed CAR T-cell therapy.

Payers were a second constraint. In Patel’s experience, some plans used by Medicaid beneficiaries do not deny CAR T-cell therapy outright but would reimburse roughly 10% of its cost, which no hospital can sustain, leaving bispecific antibodies as the only option for those patients. For other patients, Patel advised referral at the first rise in biomarkers for progression in patients on maintenance, and documenting CAR T candidacy before any salvage regimen so that authorization can be defended if a payer argues the regimen has not failed.

Response to bridging also mattered. In CARTITUDE-4 (NCT04181827), which enrolled patients with relapsed, lenalidomide-refractory disease, better response to bridging was associated with longer PFS and OS after cilta-cel.⁴ Immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 4.8% of patients (2 of 42) with a very good partial response or better, 4.3% (3 of 70) with a partial response, 4.9% (3 of 61) with minimal response or stable disease, and 35.0% (7 of 20) with progressive disease. Cranial nerve palsy followed no such pattern (11.9%, 7.1%, 8.2%, and 5.0%).⁵ Patel read the results as a reason not to wait until disease is refractory, and said the small numbers suggest only that the mechanism of cranial nerve palsy may not depend on disease burden.

Sheikh asked for guidance on prophylaxis after infusion, and other participants sought explicit instructions on how long to continue it and when to vaccinate. Patel said his program restages near day 100, returns patients to the referring oncologist, and continues antiviral and Pneumocystis jirovecii pneumonia prophylaxis for a year. Patel gives intravenous immunoglobulin monthly for 5 to 6 months and delays revaccination until patients no longer depend on it.

When asked about enabling patients 50 to 60 miles away to receive CAR T, Patel said his center’s program works with manufacturer travel assistance, social work, and a transplant house, and that ultimately, “the success of an outpatient [CAR T] program depends more on the caregiver than the patient or the program itself.”

Participants treated early referral, documented CAR T candidacy before any salvage regimen, and a caregiver and follow-up plan as the practical steps that preserve access, while payer coverage and travel distance remained barriers for some patients.

Register today to join a Case-Based Roundtable near you.

_{DISCLOSURES: Patel previously reported consulting or other fees from Abbvie, Genmab, Janssen, Kite Pharma, and Pfizer.}

REFERENCES

1. NCCN. Clinical Practice Guidelines in Oncology. Multiple myeloma, version 2.2027. Accessed September 29, 2026. https://tinyurl.com/37vy9pm2

2. Cohen AD, Mateos MV, Cohen YC, et al. Long-term (≥5-year) remission and survival with ciltacabtagene autoleucel in relapsed/refractory multiple myeloma with 1–3 prior lines of therapy: CARTITUDE-2 cohort A. Presented at: International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Poster abstract PA-59.

3. Merz M, Jelinek T, Pabst T, et al. Outcomes of CAR-T cell therapy and bispecific antibodies as single-modality and sequential strategies in relapsed/refractory multiple myeloma. Blood Cancer Discov. 2026;7(5):697-710. doi:10.1158/2643-3230.BCD-25-0461

4. Zamagni E, Dhakal B, Iida S, et al. Effectiveness of bridging therapy corresponds to improved outcomes after ciltacabtagene autoleucel: phase 3 CARTITUDE-4 study of patients with relapsed, lenalidomide-refractory multiple myeloma. Haematologica. 2026;111(suppl 2):P36. doi:10.3324/haematol.2026.s2.14045

5. Dhakal B, et al. Effectiveness of bridging therapy corresponds to improved outcomes after ciltacabtagene autoleucel: phase 3 CARTITUDE-4 study of patients with relapsed, lenalidomide-refractory multiple myeloma. Blood. 2025;146(suppl 1):2215. doi:10.1182/blood-2025-2215