Lisocabtagene Maraleucel Superior to Standard of Care for Second-Line R/R LBCL: Updates From the TRANSFORM Study

Investigators in the phase 3 TRANSFORM clinical trial compared CAR T-cell therapy, lisocabtagene maraleucel (liso-cel), versus the standard of care (SOC) for patients with second-line primary refractory/early relapsed, within 12 months or less, large B-cell lymphoma (LBCL).

Researchers randomly assigned 184 patients 1:1 eligible for autologous stem cell transplant (ASCT) to receive (liso-cel) or SOC. Of these, 89 received liso-cel and 91 started SOC, including 43 who received high-dose chemotherapy (HDCT) and ASCT. After a median follow-up of 33.9 months, patients treated with liso-cel had an event-free survival (EFS) of 29.5 months (95% CI: 9.5 to not reached), compared with 2.4 months (95% CI: 2.2 – 4.9) for those receiving standard care. The hazard ratio was 0.375 (95% CI: 0.259 to 0.542), favoring liso-cel.

After leukapheresis, removing white blood cells to prepare for HDCT and ASCT, patients were either assigned to the liso-cel arm (target dose, 100 × 10⁶ CAR⁺ T cells) or SOC. The SOC arm included three cycles of an investigator’s choice of immunochemotherapy followed by HDCT and ASCT in patients with a complete or partial response.

Following the treatment, 15 (16%) had adverse effects (AE), including prolonged cytopenia grade 3 or higher at 35 days in the liso-cel arm. Around 2 months after infusion, this group had improved to grade 2 or lower cytopenia. Rates of infections were similar in both arms. Following treatment, 2% of patients died from COVID-19-related infections, 1% had human metapneumovirus (similar to the common cold according to the Cleveland Clinic), but recovered, and 1% had pneumonia, and also recovered.

Neither arm reached median overall survival (OS). The 36-month OS rate was 63.0% for liso-cel vs 52.0% for SOC. After adjusting for crossover (66% of SOC patients received liso-cel later), the OS HR was 0.566 (95% CI: 0.359–0.895).

First author Manali Kamdar, MD, MBBS, and colleagues published the results of the three-year follow-up in the Journal of Clinical Oncology.

The team concluded that second-line liso‑cel provided significantly more durable and improved outcomes in EFS and PFS compared to SOC, with better 36-month OS and a favorable safety profile, supporting its curative potential for relapsed/refractory LBCL. Larger studies with more patients will further inform the safety, efficacy, and statistical significance of these treatments.