Biomedicine Xagena
Longer-term follow-up results from two pivotal studies of the CAR T-cell therapy Tecartus ( Brexucabtagene autoleucel; Brexu-cel ).
The three-year follow-up of ZUMA-2, a phase 2 global, multi-center study evaluating the efficacy of Tecartus in patients with relapsed / refractory ( R/R ) mantle cell lymphoma ( MCL ), and two-year follow-up of ZUMA-3, a global, multi-center, single-arm, open-label phase 1/2 study evaluating Tecartus in adult patients ( greater than or equal to 18 years old ) with R/R B-cell acute lymphoblastic leukemia ( B-ALL ) were both presented during the 2022 American Society of Clinical Oncology ( ASCO ) Annual Meeting.
At nearly three years of follow-up ( median 35.6 months ) in the ZUMA-2 trial, the overall response rate ( ORR ) was 91%, with 68% of treated patients achieving a complete response ( CR; 95% CI, 55.2–78.5 ).
The median duration of response ( DOR ) was 28.2 months, with 37% of treated patients in ongoing response at data cut-off.
Median overall survival ( OS ) among treated patients was 46.6 months.
Among those patients who achieved a complete response ( CR ), the median overall survival has not yet been reached ( 30-month OS rate was 60.3% ).
Late relapse, classified as more than 24 months post-infusion, was infrequent ( n=3 ).
In the ZUMA-3 trial, longer follow-up of the pivotal analysis and outcomes of a newly-conducted larger pooled analysis of phase 1 and 2 patients by independent review who received the pivotal dose of Tecartus were reported.
Most patients in the analysis were heavily pre-treated, with a median of two prior therapies, and 47% had received three or more prior therapies.
At a median follow-up of 29.7 months for pooled phase 1 and 2 patients, 73.1% of treated patients achieved a CR or CR with incomplete hematological recovery ( CRi ).
Median overall survival was 25.4 months for both phase 2 treated patients and pooled phase 1 and 2 treated patients.
At data cutoff, median overall survival had not yet been reached in phase 2 patients who achieved a complete response.
Similar outcomes among phase 2 treated patients ( n=55 ) and the pooled analysis of phase 1 and 2 patients ( n=78 ) were observed.
Across both trials, no new safety signal has been observed in this extended follow-up period.
In ZUMA-2, 3% of treatment-emergent adverse events of interest occurred since the primary report. The most frequent grade 3 or more adverse effects was neutropenia ( 1 [ 1% ] grade 3; 7 [ 10% ] grade 4 ).
Two patients had treatment-related grade 3 serious infections, pneumonia and upper respiratory tract infection ( n=1 ) and influenza ( n=1 ).
There were no new cytokine release syndrome adverse effects.
In ZUMA-3, no new-onset CRS, neurological events, infections, or hypogammaglobulinemia of any grade have occurred since the phase 2 primary analysis.
One new grade 5 adverse effects has occurred since the primary analysis ( graft-versus-host disease; deemed not treatment-related ).
Mantle cell lymphoma is a rare form of non-Hodgkin lymphoma ( NHL ) that arises from cells originating in the mantle zone of the lymph node and predominantly affects men over the age of 60. Approximately 33,000 people worldwide are diagnosed with mantle cell lymphoma each year.
Mantle cell lymphoma is highly aggressive following relapse, with many patients progressing following therapy.
Acute lymphoblastic leukemia is an aggressive type of blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system and other organs.
Globally, approximately 64,200 people are diagnosed with acute lymphoblastic leukemia each year. Of those, 60% of cases occur in those under age 20. Approximately 1,000 adults in the U.S. are treated annually for relapsed or refractory acute lymphoblastic leukemia.
B-cell precursor acute lymphoblastic leukemia is the most common form, accounting for approximately 75% of cases, and treatment is typically associated with inferior outcomes compared with other types of acute lymphoblastic leukemia.
Survival rates remain very poor in adult patients with relapsed or refractory acute lymphoblastic leukemia, with median overall survival at less than eight months. ( Xagena )
Source: Kite / Gilead Sciences, 2022
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