Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial

Patients with large B-cell lymphoma (LBCL) primary refractory to or relapsed within 12 months of first-line therapy are at high risk for poor outcomes with current standard of care, platinum-based salvage immunochemotherapy and autologous haematopoietic stem cell transplantation (HSCT). Lisocabtagene maraleucel (liso-cel), an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has previously demonstrated efficacy and manageable safety in third-line or later LBCL. In this Article, we report a prespecified interim analysis of liso-cel versus standard of care as second-line treatment for primary refractory or early relapsed (within 12 months after response to initial therapy) LBCL. TRANSFORM is a global, phase 3 study, conducted in 47 sites in the USA, Europe, and Japan, comparing liso-cel with standard of care as second-line therapy in patients with primary refractory or early (≤12 months) relapsed LBCL. Adults aged 18–75 years, Eastern Cooperative Oncology Group performance status score of 1 or less, adequate organ function, PET–positive disease per Lugano 2014 criteria, and candidates for autologous HSCT were randomly assigned (1:1), by use of interactive response technology, to liso-cel (100 × 106 CAR+ T cells intravenously) or standard of care. Standard of care consisted of three cycles of salvage immunochemotherapy delivered intravenously—R-DHAP (rituximab 375 mg/m2 on day 1, dexamethasone 40 mg on days 1–4, 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 1–3, and carboplatin area under the curve 5 [maximum dose of 800 mg] on day 2), or R-GDP (rituximab 375 mg/m2 on day 1, dexamethasone 40 mg on days 1–4, gemcitabine 1000 mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 1)—followed by high-dose chemotherapy and autologous HSCT in responders. Primary endpoint was event-free survival, with response assessments by an independent review committee per Lugano 2014 criteria. Efficacy was assessed per intention-to-treat (ie, all randomly assigned patients) and safety in patients who received any treatment. This trial is registered with ClinicalTrials.gov, NCT03575351, and is ongoing. Between Oct 23, 2018, and Dec 8, 2020, 232 patients were screened and 184 were assigned to the liso-cel (n=92) or standard of care (n=92) groups. At the data cutoff for this interim analysis, March 8, 2021, the median follow-