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Adults with relapsed or refractory acute lymphoblastic leukemia (ALL) have better outcomes if they have a low disease burden when receiving chimeric antigen receptor (CAR) T-cell therapy, according to research published in NEJM.
The final analysis of a phase 1 trial showed that patients with a low disease burden at baseline had superior event-free survival (EFS) and overall survival (OS) after therapy, compared to patients with a high disease burden.
Patients with a low disease burden also had a lower rate of cytokine release syndrome (CRS) and neurotoxic events.
“This is the longest follow-up study of people with ALL treated with CAR therapy,” said study author Jae Park, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
“With the long follow-up, we were able to demonstrate, for the first time, that patients with a lower disease burden benefited the most from CAR therapy, with significantly improved survival and reduced toxicity.”
The study included 53 adults with ALL who had a median age of 44 (range, 23-74).
They were heavily pretreated, with 68% receiving CAR T-cell therapy as a third or later salvage treatment. Thirty-six percent of patients had received an allogeneic transplant, and 23% had primary refractory disease.
In this trial, patients received a single infusion of 19-28z CAR T cells after conditioning chemotherapy. The maximum follow-up time was 5.5 years, with a median follow-up of 29 months.
In all, 83% of patients achieved a complete response. The median EFS was 6.1 months, and the median OS was 12.9 months.
The median EFS was significantly longer for patients with a low disease burden (<5% bone marrow blasts) compared to a high disease burden (≥5% bone marrow blasts or extramedullary disease)—10.6 months and 5.6 months, respectively (P=0.01).
The same was true for the median OS, which was 20.1 months in patients with a low disease burden and 12.4 months in those with a high disease burden (P=0.02).
For the entire study population, the rate of CRS was 85%, and 26% of patients had severe CRS. One patient died of severe CRS and multi-organ failure before the researchers began modifying the dose of CAR T cells according to the pretreatment disease burden.
Severe CRS occurred in 41% of patients with a high disease burden and 5% of those with a low disease burden.
In the entire study population, 2% of patients had grade 2 neurotoxic effects, 36% had grade 3, 6% had grade 4, and none had grade 5. The rate of severe neurotoxicity was 42%.
Neurotoxic effects occurred in 59% of patients with a high disease burden and 14% of those with a low disease burden.
“Among all of the clinical and disease factors we examined, pretreatment disease burden was the strongest predictor of long-term outcome after CAR therapy,” Dr Park said. “Our data supports the incorporation of CAR therapy in an earlier treatment setting in ALL, when the disease volume is small, so as to achieve the greatest long-term efficacy and lowest toxicity.”
This work was supported by Juno Therapeutics, the National Institutes of Health, the Carson Family Charitable Trust, the Emerald Foundation, the Mr. and Mrs. Goodwyn Commonwealth Fund, the Terry Fox Run for Cancer Research organized by the Canadian Association of New York, Kate’s Team, William Laurence and Blanche Hughes Foundation, the Center for Experimental Therapeutics at Memorial Sloan Kettering, and the Lake Road Foundation. 
Adults with relapsed or refractory acute lymphoblastic leukemia (ALL) have better outcomes if they have a low disease burden when receiving chimeric antigen receptor (CAR) T-cell therapy, according to research published in NEJM.
The final analysis of a phase 1 trial showed that patients with a low disease burden at baseline had superior event-free survival (EFS) and overall survival (OS) after therapy, compared to patients with a high disease burden.
Patients with a low disease burden also had a lower rate of cytokine release syndrome (CRS) and neurotoxic events.
“This is the longest follow-up study of people with ALL treated with CAR therapy,” said study author Jae Park, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
“With the long follow-up, we were able to demonstrate, for the first time, that patients with a lower disease burden benefited the most from CAR therapy, with significantly improved survival and reduced toxicity.”
The study included 53 adults with ALL who had a median age of 44 (range, 23-74).
They were heavily pretreated, with 68% receiving CAR T-cell therapy as a third or later salvage treatment. Thirty-six percent of patients had received an allogeneic transplant, and 23% had primary refractory disease.
In this trial, patients received a single infusion of 19-28z CAR T cells after conditioning chemotherapy. The maximum follow-up time was 5.5 years, with a median follow-up of 29 months.
In all, 83% of patients achieved a complete response. The median EFS was 6.1 months, and the median OS was 12.9 months.
The median EFS was significantly longer for patients with a low disease burden (<5% bone marrow blasts) compared to a high disease burden (≥5% bone marrow blasts or extramedullary disease)—10.6 months and 5.6 months, respectively (P=0.01).
The same was true for the median OS, which was 20.1 months in patients with a low disease burden and 12.4 months in those with a high disease burden (P=0.02).
For the entire study population, the rate of CRS was 85%, and 26% of patients had severe CRS. One patient died of severe CRS and multi-organ failure before the researchers began modifying the dose of CAR T cells according to the pretreatment disease burden.
Severe CRS occurred in 41% of patients with a high disease burden and 5% of those with a low disease burden.
In the entire study population, 2% of patients had grade 2 neurotoxic effects, 36% had grade 3, 6% had grade 4, and none had grade 5. The rate of severe neurotoxicity was 42%.
Neurotoxic effects occurred in 59% of patients with a high disease burden and 14% of those with a low disease burden.
“Among all of the clinical and disease factors we examined, pretreatment disease burden was the strongest predictor of long-term outcome after CAR therapy,” Dr Park said. “Our data supports the incorporation of CAR therapy in an earlier treatment setting in ALL, when the disease volume is small, so as to achieve the greatest long-term efficacy and lowest toxicity.”
This work was supported by Juno Therapeutics, the National Institutes of Health, the Carson Family Charitable Trust, the Emerald Foundation, the Mr. and Mrs. Goodwyn Commonwealth Fund, the Terry Fox Run for Cancer Research organized by the Canadian Association of New York, Kate’s Team, William Laurence and Blanche Hughes Foundation, the Center for Experimental Therapeutics at Memorial Sloan Kettering, and the Lake Road Foundation.
Adults with relapsed or refractory acute lymphoblastic leukemia (ALL) have better outcomes if they have a low disease burden when receiving chimeric antigen receptor (CAR) T-cell therapy, according to research published in NEJM.
The final analysis of a phase 1 trial showed that patients with a low disease burden at baseline had superior event-free survival (EFS) and overall survival (OS) after therapy, compared to patients with a high disease burden.
Patients with a low disease burden also had a lower rate of cytokine release syndrome (CRS) and neurotoxic events.
“This is the longest follow-up study of people with ALL treated with CAR therapy,” said study author Jae Park, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
“With the long follow-up, we were able to demonstrate, for the first time, that patients with a lower disease burden benefited the most from CAR therapy, with significantly improved survival and reduced toxicity.”
The study included 53 adults with ALL who had a median age of 44 (range, 23-74).
They were heavily pretreated, with 68% receiving CAR T-cell therapy as a third or later salvage treatment. Thirty-six percent of patients had received an allogeneic transplant, and 23% had primary refractory disease.
In this trial, patients received a single infusion of 19-28z CAR T cells after conditioning chemotherapy. The maximum follow-up time was 5.5 years, with a median follow-up of 29 months.
In all, 83% of patients achieved a complete response. The median EFS was 6.1 months, and the median OS was 12.9 months.
The median EFS was significantly longer for patients with a low disease burden (<5% bone marrow blasts) compared to a high disease burden (≥5% bone marrow blasts or extramedullary disease)—10.6 months and 5.6 months, respectively (P=0.01).
The same was true for the median OS, which was 20.1 months in patients with a low disease burden and 12.4 months in those with a high disease burden (P=0.02).
For the entire study population, the rate of CRS was 85%, and 26% of patients had severe CRS. One patient died of severe CRS and multi-organ failure before the researchers began modifying the dose of CAR T cells according to the pretreatment disease burden.
Severe CRS occurred in 41% of patients with a high disease burden and 5% of those with a low disease burden.
In the entire study population, 2% of patients had grade 2 neurotoxic effects, 36% had grade 3, 6% had grade 4, and none had grade 5. The rate of severe neurotoxicity was 42%.
Neurotoxic effects occurred in 59% of patients with a high disease burden and 14% of those with a low disease burden.
“Among all of the clinical and disease factors we examined, pretreatment disease burden was the strongest predictor of long-term outcome after CAR therapy,” Dr Park said. “Our data supports the incorporation of CAR therapy in an earlier treatment setting in ALL, when the disease volume is small, so as to achieve the greatest long-term efficacy and lowest toxicity.”
This work was supported by Juno Therapeutics, the National Institutes of Health, the Carson Family Charitable Trust, the Emerald Foundation, the Mr. and Mrs. Goodwyn Commonwealth Fund, the Terry Fox Run for Cancer Research organized by the Canadian Association of New York, Kate’s Team, William Laurence and Blanche Hughes Foundation, the Center for Experimental Therapeutics at Memorial Sloan Kettering, and the Lake Road Foundation.