|The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Lisocabtagene maraleucel (liso-cel) demonstrated promising clinical activity with low rates of grade 3 or higher cytokine release syndrome (CRS) and neurotoxicity among patients with relapsed/refractory mantle cell lymphoma (MCL), according to results of a phase 1 study presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
Relapsed MCL is associated with poor response to salvage therapy. Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy has demonstrated promising efficacy in other subtypes of non-Hodgkin lymphoma.
Liso-cel is a CD19-directed, 4-1BB CAR-T product administered as separate CD8-positive and CD4-positive CAR-positive T-cell components at equal doses.
“The objective of this study was to determine the safety and initial antitumor activity of liso-cel in patients with relapsed/refractory MCL from the TRANSCEND study,” Maria Lia Palomba, MD, of Memorial Sloan Kettering Cancer Center in New York City, and presenter of the study, said.
The phase 1 study included a cohort of 32 patients with relapsed/refractory MCL treated with liso-cel at 1 of 2 doses. All patients received lymphodepleting chemotherapy, and bridging therapy was allowed between leukapheresis and lymphodepletion. The coprimary endpoints were safety and objective response rate (ORR). The secondary endpoints included complete response (CR) rate, duration of response, progression-free survival (PFS), and overall survival (OS).
At baseline, the median age of patients in the cohort was 67 years, and 84% were male. Blastoid morphology was present in 41% of patients, Ki67 was 30% or higher among 72% of patients, TP53 mutations was found among 22% of patients, and a complex karyotype was seen in 34% of patients. The median number of prior lines of therapy was 3 (range, 1-7) and 81% of participants were refractory to their last treatment.
Among evaluable patients, the overall ORR was 84%, with a CR rate of 66%. The ORR benefit was 83% for patients with a Ki67 of 30% or higher, at 77% in those with blastoid morphology, and in 100% of those harboring TP53 mutations. The median duration of response was not yet reached, with a median follow-up of 3.9 months.
“A total of 6 patients have demonstrated a durable response of over 1 year in this ongoing study,” Dr Palomba said.
The median time to liso-cel expansion was 10 days after infusion, and persisted for at 1 year among 67% of patients and 2 years among 33% of patients with sufficient follow-up.
Serious treatment-emergent adverse events (TEAEs) developed in 56% of patients, with the most common grade 3 or higher TEAEs including neutropenia, anemia, and thrombocytopenia. Cytokine release syndrome occurred in 50% of patients, with 1 grade 4 event and no grade 3 or 5 events. Neurotoxicity occurred in 34% of patients, including 3 grade 3 events and no grade 4 or 5 events.
Dr Palomba concluded that these results suggest that liso-cel is “associated with promising clinical activity and a low incidence of grade 3 or higher CRS and neurologic events.”
Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ASH 2020 meeting by visiting the conference page.
Palomba ML, Gordon LI, Siddiqi T, et al. Safety and preliminary efficacy in patients with relapsed/refractory mantle cell lymphoma receiving lisocabtagene maraleucel in Transcend NHL 001. Presented at: 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-9, 2020. Abstract 118.