B-ALL: New Findings Confirm Efficacy of CAR T Product

Chicago — The latest findings from the FELIX phase 1b/2 study confirm the efficacy of obecabtagene autoleucel (obe-cel/Auto1, Autolus Therapeutics) and establish the CD19-directed autologous chimeric antigen receptor (CAR) T-cell product as a standard-of-care therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.

Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.

At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.

The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.

“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.

Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.

“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.

The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.

Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.

Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.

The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.

This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.

Chicago — The latest findings from the FELIX phase 1b/2 study confirm the efficacy of obecabtagene autoleucel (obe-cel/Auto1, Autolus Therapeutics) and establish the CD19-directed autologous chimeric antigen receptor (CAR) T-cell product as a standard-of-care therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.

Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.

At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.

The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.

“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.

Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.

“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.

The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.

Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.

Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.

The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.

This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.

Chicago — The latest findings from the FELIX phase 1b/2 study confirm the efficacy of obecabtagene autoleucel (obe-cel/Auto1, Autolus Therapeutics) and establish the CD19-directed autologous chimeric antigen receptor (CAR) T-cell product as a standard-of-care therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.

The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.

Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.

At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.

The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.

“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.

Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.

“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.

The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.

Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.

Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.

The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.

This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.