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December 17, 2020 - Lisocabtagene maraleucel exhibited promising antitumor activity with low rates of grade 3 or higher cytokine release syndrome and neurotoxicity in patients with relapsed/refractory mantle cell lymphoma.
Lisocabtagene maraleucel (liso-cel) exhibited promising antitumor activity with low rates of grade 3 or higher cytokine release syndrome (CRS) and neurotoxicity in patients with relapsed/refractory mantle cell lymphoma (MCL), according to phase 1 results of the single-arm TRANSCEND NHL 001 trial that were presented during the 2020 ASH Annual Meeting and Exposition.1
The objective response rate (ORR) among the 32 patients treated in the study was 84%, with a complete response (CR) rate of 66% at a median on-study follow-up of 5.9 months, lead study reported Maria Lia Palomba, MD, reported in a presentation during the virtual meeting.
The median time to first CR or partial response was 0.95 months.
“The median duration of response was not reached after a median follow-up of 3.9 months,” said Palomba, a hematologist/oncologist, Memorial Sloan Kettering Cancer Center. “A total of 6 patients have demonstrated a durable response over 1 year in this ongoing study. Importantly, responses were generally similar in patients with blastoid morphology and in patients who were resistant to ibrutinib [Imbruvica].”
Among the patients with Ki-67 level at 30% or higher, the ORR was 83% and the CR rate was 65%. Of those with blastoid morphology, the ORR and CR rates were 77% and 54%, respectively, and among patients with a TP53 mutation, these rates were 100% and 57%, respectively.
Prognosis is poor in patients with MCL, with disease progression likely following receipt of a BTK inhibitor. The median overall survival with salvage therapy is typically 6 to 10 months.2-4 Liso-cell previously demonstrated an ORR of 73%, with a CR rate of 53%, among a subcohort of patients with relapsed/refractory large B-cell lymphoma who were enrolled on TRANSCEND NHL 001, in whom the rate of grade 3 or higher CRS was 2% and neurologic events occurred in 10% of these patients.5
Liso-cel, a CD19-directed, 4-1BB CAR T-cell product, is administered as separate CD8+ and CD4+ T-cell components at equal target doses. “Importantly, the defined dose and CD8+/CD4+ ratio [of CAR T cells] may influence the incidence and severity of CRS and neurologic events,” she said.
At data cutoff, the relapsed/refractory MCL cohort consisted of 32 patients who, after lymphodepletion, were treated with liso-cel at 1 of 2 dose levels—6 at dose level 1 (50 x 106 CAR T cells) and 26 at dose level 2 (100 x 106 CAR T cells). Administration of CAR T cells and monitoring were allowed in either the inpatient or outpatient setting. Bridging therapy was permitted and could include chemotherapy or radiotherapy. Eligible patients had at least 2 prior lines of therapy.
“After a protocol amendment, patients were required to have received a BTK inhibitor, an alkylating agent, and an anti-CD20 agent,” said Palomba.
The primary end points were adverse events (AEs), dose-limiting toxicities, and ORR by independent review committee per Lugano classification.
The median time to maximal liso-cel expansion was 10 days after infusion. “Liso-cel showed long-term persistence at 1 year in 67% of patients and at 2 years in 33% of patients with sufficient follow-up,” she said.
The median age was 67 years, 41% had blastoid morphology, 72% had documented Ki-67 at least 30%, and 22% had TP53 mutations. Patients received a median of 3 prior lines of therapy, 81% had disease refractory to their most recent prior therapy, and 31% were refractory to prior ibrutinib.
Eighty-four percent had a grade 3 or higher treatment-emergent (TEAE), including anemia (38%), neutropenia (44%), and thrombocytopenia (31%). Prolonged grade 3 and higher cytopenias present at study day 29 were reported in 34% of patients.
Two grade-5 treatment-emergent adverse events occurred in 2 patients, both at dose level 2 and both were considered related to liso-cel: 1 patient experienced tumor lysis syndrome and 1 patient with cryptococcal meningoencephalitis died. There were no deaths related to CRS or neurologic events.
Grade 3 or higher CRS was reported in 1 patient (3%), with a median time to onset of 6 days and a median to resolution of 4 days. Grade 3 or higher neurologic events were reported in 4 (12.5%), with a median time to onset of 8 days and a median time to resolution of 4 days. For management of CRS and neurologic events, 12.5% of patients required both tocilizumab (Actemra) and corticosteroids, 12.5% required corticosteroids alone, and 6% tocilizumab only.
Enrollment into the study is ongoing at dose level 2 in the MCL cohort, said Palomba.