Findings from the phase 2 TRANSCEND-PILOT-017006 supported the use of lisocabtagene maraleucel as a second-line treatment for patients with large B-cell lymphoma who were not able to or didn’t want to receive hematopoietic stem cell transplant.
Lisocabtagene maraleucel (liso-cel; Breyanzi) as a second-line treatment for patients with large B-cell lymphoma not intended for hematopoietic stem cell transplant was further supported by findings from the phase 2 TRANSCEND-PILOT-017006 study (NCT03483103).
The median on-study follow-up was 12.3 months, during which the objective response rate was 80% (95% CI, 68%-89%), with 54% (95% CI, 41%-67%) of patients having a best overall response of complete response (CR). Within 1 year of first-line therapy, 21% of patients relapsed and 25% relapsed after 12 months.
A total of 74 patients underwent leukapheresis, 61 received liso-cel and had confirmed PET-positive disease, and 1 patient received a non-conforming product. There were 12 patients who underwent leukapheresis and did not receive liso-cel, 4 of whom had progressed. Of these patients 3 had died and 1 was admitted to hospice. From leukapheresis to product release, the median time was 24 days with the median time from leukapheresis to liso-cel infusion being 35.5 days.
Among those receiving liso-cel, 41 patients met the protocol criteria, 31 met the age requirement, 6 met the ECOG performance, 3 met the creatine clearance, and 1 met the diffusing lung capacity for carbon monoxide.
The median follow-up was 13.0 months and the median progression-free survival (PFS) was 9.03 months (95% CI, 4.17–not reached [NR]). At a median follow-up of 16.4 months, the median event-free survival was 7.23 months (95% CI, 3.22-22.60). At 17.6 months, the median overall survival (OS) was not reached (95% CI, 17.28-NR).
Forty-nine patients had a CR or partial response, with a median duration of response (DOR) of 12.09 months (95% CI, 6.24-NR). Of those with a CR, the median PFS was 22.60 months (95% CI, 12.98-NR) and the OS was also not reached. Additionally, the median DOR among those with durable responses was 21.65 months (95% CI, 12.09-NR). The post-hoc analysis showed the median time to first response and first CR was 0.95 months in each group, respectively.
The most frequent treatment-emergent adverse effects (TRAEs) included neutropenia, fatigue, cytokine release syndrome (CRS), and anemia. The most common grade 3 TRAEs were neutropenia (48%), leukopenia (21%), and thrombocytopenia (20%). A total of 2 patients died from TRAEs, 1 from COVID-19 after liso-cel infusion, and one from COVID-19 pneumonia. Serious TRAEs related to liso-cel infusion were observed in 21% of patients. Of note, no AEs led to discontinuation and no other TRAEs had occurred.
CRS was observed in 21 patients, 26% of whom were treated with tocilizumab. Grade 3 neurological events presented in 5% of patients, with 1 patient each having aphasia and confusional state, confusional state and encephalopathy, and dysphasia, with all resolving within 5 days. In 13% of patients, neurological events were managed with corticosteroids, and no grade 4 or 5 CRS occurred.
Thirty percent of patients experienced prolonged grade 3 AEs cytopenias, with most patients moving to grade 2 cytopenias by day 90. Sepsis and COVID-19 were the cause of 2 prolonged cytopenias with non-relapse mortality in 2 patients.
TRAEs of special interest included hypogammaglobulinemia in 8% of patients and grade 3 or higher infection in 7% of patients. There were 41 patients who were treated in the inpatient setting and were admitted to the intensive care unit at any time for CRS with or without neurological symptoms. Of those who were in the outpatient setting, 45% were admitted to the hospital and 5% were admitted to the intensive care unit for a pulmonary embolism.
Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. Published Online July 12, 2022. doi:10.1016/S1470-2045(22)00339-4