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It’s early days, but preliminary data show that a chimeric antigen receptor T-cell therapy (CAR T) product was associated with high rates of minimal residual disease (MRD) negativity, and complete or near-complete responses in children and adolescents with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL).
Among 24 patients aged 3-20 years with relapsed or refractory B-ALL treated with the CAR T construct brexucabtagene autoleucel (KTE-X19; Tecartus), 16 had either a complete response or CR with incomplete recovery of blood counts (CRi), for a combined CR/CRi rate of 67%, reported Alan S. Wayne, MD, from Children’s Hospital Los Angeles and the University of Southern California Norris Comprehensive Cancer Center, also in Los Angeles.
“Optimized KTE-X19 formulation of 40 mL and revised toxicity management were associated with an improved risk/benefit profile,” he said in audio narration accompanying a poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.
Although overall survival for children and adolescents receiving first-line therapy for B-ALL is associated with remission rates of 80% or more, the prognosis is poor following relapse, despite the availability of newer therapies such as blinatumomab (Blincyto) and inotuzumab (Besponsa), with a 1-year overall survival rate of approximately 36%, he said.
To see whether they could improve on these odds, Dr. Wayne and colleagues conducted the phase 1 Zuma-4 trial, a single-arm, open-label study in children and adolescents with relapsed/refractory B-ALL.
He reported long-term follow-up results from the study.
Zuma-4 details
A total of 24 patients, median age 14 (range 3 to 20) years, received the CAR T product. Four patients received the starting dose of 2 x 106 CAR T per kg (these patients were enrolled per protocol for evaluation of dose-limiting toxicities).
Following the initial dosing and evaluation of safety, 11 patients were treated with a dose of 1 x 106 cells per kg with a total volume of 68 mL, and 9 received 1 x 106 per kg at a volume of 40 mL (the dose being used in current phase 2 trials).
The median follow-up at the time of data cutoff in September 2020 was 36.1 months.
The combined CR/CRi rate was 75% for patients treated at the starting dose, 64% for patients treated at the 1 x 106 68-mL dose, and 67% for those who received the 48-mL dose.
The respective median durations of response were 4.14 months, 10.68 months, and not reached.
All patients who had an objective response had undetectable MRD assessed by flow cytometry with a sensitivity of .01%.
The therapy served as a bridge to allogeneic transplant in 16 patients, including 2 in the initial dose group, 8 in the 68-mL group, and 6 in the 40-mL group.
Median overall survival was not reached in either of the two 1 x 106–dose groups, but was 8 months in the 2 x 106 group.
There were no dose-limiting toxicities seen, and the adverse event profile was consistent with that seen with the use of CAR T therapy for other malignancies.
Patients treated at either the 68-mL or 40-mL 1 x 106–dose levels received tocilizumab only for neurologic events occurring in context with the cytokine release syndrome (CRS), and were started on steroids for grade 2 or greater neurologic events.
Rates of grade 3 or greater neurologic events were 25% in the initial-dose group, 27% in the 68-mL group, and 11% in the 40-mL group. Respective rates of grade 3 or greater CRS were 75%, 27%, and 22%.
Four patients died on study, all from causes deemed unrelated to CAR T therapy: two from progressive disease, one from disseminated mucormycosis, and one from Escherichia sepsis.
Investigators are currently enrolling pediatric patients with relapsed/refractory B-ALL or non-Hodgkin lymphoma, including patients with MRD-positive disease and early relapse after first-line therapy, in phase 2 of the Zuma-4 study.
How long will it last?
Howard Weinstein, MD, chief of pediatric hematology/oncology at Mass General for Children in Boston, who was not involved in the study, said in an interview that the response rate and comparatively low toxicity profile look good.
“One of the challenges, though, with CAR T-cell products has been relapse – almost half of the patients who go into remission relapse. Sometimes leukemic cells change their surface properties, resulting in antigen loss, there’s T-cell exhaustion, and other postulates for relapse,” he said.
He noted that due to the high number of patients who went on to transplant, the study lacks good data on the durability of remissions.
“One of the unknowns at the moment is whether CAR T cells are sufficient to cure a high percentage of children who have had a relapse, or do you need to follow it with a bone marrow transplant,” Dr. Weinstein said.
The ZUMA-4 trial is sponsored by Kite Pharma. Dr. Wayne disclosed research funding from Kite, Servier, and Institut de Recherches Internationales. Dr. Weinstein had no relevant disclosures.
It’s early days, but preliminary data show that a chimeric antigen receptor T-cell therapy (CAR T) product was associated with high rates of minimal residual disease (MRD) negativity, and complete or near-complete responses in children and adolescents with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL).
Among 24 patients aged 3-20 years with relapsed or refractory B-ALL treated with the CAR T construct brexucabtagene autoleucel (KTE-X19; Tecartus), 16 had either a complete response or CR with incomplete recovery of blood counts (CRi), for a combined CR/CRi rate of 67%, reported Alan S. Wayne, MD, from Children’s Hospital Los Angeles and the University of Southern California Norris Comprehensive Cancer Center, also in Los Angeles.
“Optimized KTE-X19 formulation of 40 mL and revised toxicity management were associated with an improved risk/benefit profile,” he said in audio narration accompanying a poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.
Although overall survival for children and adolescents receiving first-line therapy for B-ALL is associated with remission rates of 80% or more, the prognosis is poor following relapse, despite the availability of newer therapies such as blinatumomab (Blincyto) and inotuzumab (Besponsa), with a 1-year overall survival rate of approximately 36%, he said.
To see whether they could improve on these odds, Dr. Wayne and colleagues conducted the phase 1 Zuma-4 trial, a single-arm, open-label study in children and adolescents with relapsed/refractory B-ALL.
He reported long-term follow-up results from the study.
Zuma-4 details
A total of 24 patients, median age 14 (range 3 to 20) years, received the CAR T product. Four patients received the starting dose of 2 x 106 CAR T per kg (these patients were enrolled per protocol for evaluation of dose-limiting toxicities).
Following the initial dosing and evaluation of safety, 11 patients were treated with a dose of 1 x 106 cells per kg with a total volume of 68 mL, and 9 received 1 x 106 per kg at a volume of 40 mL (the dose being used in current phase 2 trials).
The median follow-up at the time of data cutoff in September 2020 was 36.1 months.
The combined CR/CRi rate was 75% for patients treated at the starting dose, 64% for patients treated at the 1 x 106 68-mL dose, and 67% for those who received the 48-mL dose.
The respective median durations of response were 4.14 months, 10.68 months, and not reached.
All patients who had an objective response had undetectable MRD assessed by flow cytometry with a sensitivity of .01%.
The therapy served as a bridge to allogeneic transplant in 16 patients, including 2 in the initial dose group, 8 in the 68-mL group, and 6 in the 40-mL group.
Median overall survival was not reached in either of the two 1 x 106–dose groups, but was 8 months in the 2 x 106 group.
There were no dose-limiting toxicities seen, and the adverse event profile was consistent with that seen with the use of CAR T therapy for other malignancies.
Patients treated at either the 68-mL or 40-mL 1 x 106–dose levels received tocilizumab only for neurologic events occurring in context with the cytokine release syndrome (CRS), and were started on steroids for grade 2 or greater neurologic events.
Rates of grade 3 or greater neurologic events were 25% in the initial-dose group, 27% in the 68-mL group, and 11% in the 40-mL group. Respective rates of grade 3 or greater CRS were 75%, 27%, and 22%.
Four patients died on study, all from causes deemed unrelated to CAR T therapy: two from progressive disease, one from disseminated mucormycosis, and one from Escherichia sepsis.
Investigators are currently enrolling pediatric patients with relapsed/refractory B-ALL or non-Hodgkin lymphoma, including patients with MRD-positive disease and early relapse after first-line therapy, in phase 2 of the Zuma-4 study.
How long will it last?
Howard Weinstein, MD, chief of pediatric hematology/oncology at Mass General for Children in Boston, who was not involved in the study, said in an interview that the response rate and comparatively low toxicity profile look good.
“One of the challenges, though, with CAR T-cell products has been relapse – almost half of the patients who go into remission relapse. Sometimes leukemic cells change their surface properties, resulting in antigen loss, there’s T-cell exhaustion, and other postulates for relapse,” he said.
He noted that due to the high number of patients who went on to transplant, the study lacks good data on the durability of remissions.
“One of the unknowns at the moment is whether CAR T cells are sufficient to cure a high percentage of children who have had a relapse, or do you need to follow it with a bone marrow transplant,” Dr. Weinstein said.
The ZUMA-4 trial is sponsored by Kite Pharma. Dr. Wayne disclosed research funding from Kite, Servier, and Institut de Recherches Internationales. Dr. Weinstein had no relevant disclosures.
It’s early days, but preliminary data show that a chimeric antigen receptor T-cell therapy (CAR T) product was associated with high rates of minimal residual disease (MRD) negativity, and complete or near-complete responses in children and adolescents with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL).
Among 24 patients aged 3-20 years with relapsed or refractory B-ALL treated with the CAR T construct brexucabtagene autoleucel (KTE-X19; Tecartus), 16 had either a complete response or CR with incomplete recovery of blood counts (CRi), for a combined CR/CRi rate of 67%, reported Alan S. Wayne, MD, from Children’s Hospital Los Angeles and the University of Southern California Norris Comprehensive Cancer Center, also in Los Angeles.
“Optimized KTE-X19 formulation of 40 mL and revised toxicity management were associated with an improved risk/benefit profile,” he said in audio narration accompanying a poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.
Although overall survival for children and adolescents receiving first-line therapy for B-ALL is associated with remission rates of 80% or more, the prognosis is poor following relapse, despite the availability of newer therapies such as blinatumomab (Blincyto) and inotuzumab (Besponsa), with a 1-year overall survival rate of approximately 36%, he said.
To see whether they could improve on these odds, Dr. Wayne and colleagues conducted the phase 1 Zuma-4 trial, a single-arm, open-label study in children and adolescents with relapsed/refractory B-ALL.
He reported long-term follow-up results from the study.
Zuma-4 details
A total of 24 patients, median age 14 (range 3 to 20) years, received the CAR T product. Four patients received the starting dose of 2 x 106 CAR T per kg (these patients were enrolled per protocol for evaluation of dose-limiting toxicities).
Following the initial dosing and evaluation of safety, 11 patients were treated with a dose of 1 x 106 cells per kg with a total volume of 68 mL, and 9 received 1 x 106 per kg at a volume of 40 mL (the dose being used in current phase 2 trials).
The median follow-up at the time of data cutoff in September 2020 was 36.1 months.
The combined CR/CRi rate was 75% for patients treated at the starting dose, 64% for patients treated at the 1 x 106 68-mL dose, and 67% for those who received the 48-mL dose.
The respective median durations of response were 4.14 months, 10.68 months, and not reached.
All patients who had an objective response had undetectable MRD assessed by flow cytometry with a sensitivity of .01%.
The therapy served as a bridge to allogeneic transplant in 16 patients, including 2 in the initial dose group, 8 in the 68-mL group, and 6 in the 40-mL group.
Median overall survival was not reached in either of the two 1 x 106–dose groups, but was 8 months in the 2 x 106 group.
There were no dose-limiting toxicities seen, and the adverse event profile was consistent with that seen with the use of CAR T therapy for other malignancies.
Patients treated at either the 68-mL or 40-mL 1 x 106–dose levels received tocilizumab only for neurologic events occurring in context with the cytokine release syndrome (CRS), and were started on steroids for grade 2 or greater neurologic events.
Rates of grade 3 or greater neurologic events were 25% in the initial-dose group, 27% in the 68-mL group, and 11% in the 40-mL group. Respective rates of grade 3 or greater CRS were 75%, 27%, and 22%.
Four patients died on study, all from causes deemed unrelated to CAR T therapy: two from progressive disease, one from disseminated mucormycosis, and one from Escherichia sepsis.
Investigators are currently enrolling pediatric patients with relapsed/refractory B-ALL or non-Hodgkin lymphoma, including patients with MRD-positive disease and early relapse after first-line therapy, in phase 2 of the Zuma-4 study.
How long will it last?
Howard Weinstein, MD, chief of pediatric hematology/oncology at Mass General for Children in Boston, who was not involved in the study, said in an interview that the response rate and comparatively low toxicity profile look good.
“One of the challenges, though, with CAR T-cell products has been relapse – almost half of the patients who go into remission relapse. Sometimes leukemic cells change their surface properties, resulting in antigen loss, there’s T-cell exhaustion, and other postulates for relapse,” he said.
He noted that due to the high number of patients who went on to transplant, the study lacks good data on the durability of remissions.
“One of the unknowns at the moment is whether CAR T cells are sufficient to cure a high percentage of children who have had a relapse, or do you need to follow it with a bone marrow transplant,” Dr. Weinstein said.
The ZUMA-4 trial is sponsored by Kite Pharma. Dr. Wayne disclosed research funding from Kite, Servier, and Institut de Recherches Internationales. Dr. Weinstein had no relevant disclosures.
FROM ASPHO 2021