Clinical trialPhase 3Lymphoma

Lisocabtagene Maraleucel Versus Standard of Care for Second-Line Relapsed/Refractory Large B-Cell Lymphoma: 3-Year Follow-Up From the Randomized, Phase III TRANSFORM Study

J Clin Oncol · 2025184 patients

Kamdar M, Solomon SR, Arnason J, et al. J Clin Oncol. 2025. 43:2671-2678

Study type: Clinical trial
Study name: TRANSFORM
Phase: Phase 3
Design: Randomised trial (1:1); descriptive 3-year follow-up report (median follow-up 33.9 months)
Sample size: 184 patients
Source: J Clin Oncol · 2025
Trial registration: NCT03575351

In plain words

When large B-cell lymphoma does not respond to the first treatment or comes back within the first year, the traditional approach is more chemotherapy followed by a stem cell transplant. In the TRANSFORM study, a newer approach called CAR-T cell therapy (lisocabtagene maraleucel) was compared with this traditional approach; in CAR-T therapy, the patient's own immune cells are changed in the laboratory so that they recognise and destroy lymphoma cells. After about three years, about half of the patients in the CAR-T group were free of disease growth, compared with about a quarter in the standard-treatment group. Many patients in the standard group later received CAR-T, which is why the difference in length of life looks smaller.

Key results

29.5 months vs 2.4 months

Median event-free survival

HR 0.375 (95% CI 0.259 to 0.542)

51% vs 26.5%

36-month progression-free survival

Median: not reached vs 6.2 months; HR 0.422 (95% CI 0.279 to 0.639)

63% vs 52%

36-month overall survival

HR 0.757 (95% CI 0.481 to 1.191); 66% of standard-of-care patients crossed over to liso-cel

HR 0.566

Overall survival adjusted for crossover

95% CI 0.359 to 0.895; favours liso-cel

Drugs in this study:Carboplatin (Paraplatin)Cisplatin (Platinol)Cyclophosphamide (Endoxan)Gemcitabine (Gemzar)Rituximab (Rituxan/MabThera)

Dose and schedule cards

Second-line CAR T-cell therapy: axicabtagene ciloleucel (ZUMA-7) or lisocabtagene maraleucel (TRANSFORM)

Large B-cell lymphoma refractory to first-line treatment or relapsing within 12 months of it (candidates for intensive therapy)Cycle length: Single doseOn the page “Lymphoma” · Treatment regimens and dosing: relapsed or refractory DLBCL, eligible for transplantation or CAR T-cell therapy

Large B-cell lymphoma refractory to first-line treatment or relapsing within 12 months of it (candidates for intensive therapy)

Drug	Dose	Route	Schedule
Axi-cel: lymphodepletion
Cyclophosphamide	500 mg/m²	IV	Days −5, −4 and −3 before infusion
Fludarabine	30 mg/m²	IV	Days −5, −4 and −3 before infusion
Axi-cel
Axicabtagene ciloleucel	2 × 10⁶ CAR-positive viable T cells/kg (maximum 2 × 10⁸ cells)	IV	Once, Day 0
Liso-cel: lymphodepletion
Fludarabine	30 mg/m² daily	IV	3 days
Cyclophosphamide	300 mg/m² daily	IV	3 days
Liso-cel
Lisocabtagene maraleucel	90 to 110 × 10⁶ CAR-positive viable T cells	IV	Once, 2 to 7 days after completion of lymphodepletion

Cycle length: Single dose
Duration: One-time infusion

Doses from the FDA labels for YESCARTA and BREYANZI. Before infusion, acetaminophen and an H1 antihistamine; tocilizumab and emergency equipment must be available; the patient should stay near the treatment centre for at least 2 weeks after axi-cel infusion. In ZUMA-7, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21% of patients. In renal impairment, adjust the fludarabine and cyclophosphamide doses according to the labels of these drugs.

On the page “Lymphoma” · Treatment regimens and dosing: relapsed or refractory DLBCL, eligible for transplantation or CAR T-cell therapy

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Lisocabtagene maraleucel (liso-cel)

Lymphodepleting chemotherapy with fludarabine 30 mg/m²/day and cyclophosphamide 300 mg/m²/day given together for 3 days, then 2 to 7 days later a single infusion of lisocabtagene maraleucel at a dose of 100 × 10⁶ CAR-positive T cells.

2Standard of care

Three cycles of IV salvage chemoimmunotherapy, followed by high-dose chemotherapy and autologous transplantation in responders: R-DHAP (rituximab 375 mg/m² on day 1, dexamethasone 40 mg on days 1 to 4, two infusions of cytarabine 2000 mg/m² on day 2 and cisplatin 100 mg/m² on day 1), R-ICE (rituximab 375 mg/m² on day 1, ifosfamide 5000 mg/m² on day 2, etoposide 100 mg/m² on days 1 to 3 and carboplatin AUC 5 [maximum 800 mg] on day 2) or R-GDP (rituximab 375 mg/m² on day 1, dexamethasone 40 mg on days 1 to 4, gemcitabine 1000 mg/m² on days 1 and 8 and cisplatin 75 mg/m² on day 1).

Source of the regimen details: Abstract of the primary TRANSFORM report (Lancet 2022) for the liso-cel dose and standard regimens; FDA label for BREYANZI (Clinical Studies section, TRANSFORM) for the lymphodepleting regimen

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults with large B-cell lymphoma (LBCL) that was primary refractory or relapsed early (12 months or less after first-line therapy) who were eligible for autologous stem cell transplantation.

Endpoints

Reported outcomes (descriptive): event-free survival (EFS), progression-free survival (PFS), overall survival (OS) and safety.

Safety and side effects

Safety results were consistent with previous reports, and no new safety signals were seen at 3-year follow-up. In the primary TRANSFORM report, the most common grade 3 or higher adverse events (liso-cel versus standard of care) were neutropenia 80% versus 51%, anaemia 49% versus 49%, thrombocytopenia 49% versus 64% and prolonged cytopenia 43% versus 3%; grade 3 cytokine release syndrome occurred in 1% and grade 3 neurological events in 4%.

Clinical significance and place in guidelines

The 3-year follow-up confirms the durable superiority of liso-cel over standard of care in event-free and progression-free survival in primary refractory or early-relapsed LBCL. The overall survival difference was not conclusive in the main analysis but favoured liso-cel after adjustment for crossover. These results strengthen the place of second-line CAR-T for this high-risk group.

Limitations

The results are reported descriptively. Crossover of 66% of standard-of-care patients to liso-cel makes the overall survival comparison difficult, and the crossover-adjusted analysis relies on statistical assumptions. The sample size (184 patients) is relatively small, and only transplant-eligible patients were enrolled.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.