BLINATUMOMAB IMPROVED OVERALL SURVIVAL IN PATIENTS WITH RELAPSED OR REFRACTORY PHILADELPHIA NEGATIVE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA IN A RANDOMIZED, OPEN-LABEL PHASE 3 STUDY (TOWER)
(Abstract release date: 05/19/16)
EHA Library. Topp M. 06/10/16; 135182; S149
Topic: 3Aa B lymphoblastic leukemia/lymphomaDisclosure(s): Universitätsklinikum Würzburg
Dr. Max Topp
Contributions
Contributions
Abstract
Abstract: S149
Type: Presidential Symposium
Presentation during EHA21: On Friday, June 10, 2016 from 16:35 - 16:47
Location: Hall A1
Background
Blinatumomab, a bispecific T-cell engager antibody construct, binds specifically to CD19 (B cells) and CD3 (T cells) to facilitate lysis of CD19-positive target B-lineage cells. Based on a single-arm phase 2 study, blinatumomab received approvals in the US (accelerated) and EU (conditional) for the treatment of Philadelphia chromosome-negative (Ph–) relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Aims
This phase 3, randomized, open-label study investigated the effect of blinatumomab on overall survival (OS) compared with standard of care (SOC) chemotherapy in adult patients with Ph– r/r BCP-ALL.
Methods
Patients with r/r BCP-ALL (if first relapse, within 1 y) were randomized 2:1 to receive either blinatumomab or SOC chemotherapy (investigator's choice of 1 of 4 defined regimens). Randomization was stratified by age, prior salvage therapy, and prior allogeneic stem cell transplant (alloSCT). Blinatumomab was given in 6-week cycles of 4 weeks on (continuous infusion of 9 µg/d in week 1 of cycle 1, then 28 µg/d) and 2 weeks off; dexamethasone was given pre-dose to prevent cytokine release syndrome. Patients in remission after 2 induction cycles were eligible to continue therapy until relapse. OS was the primary efficacy endpoint. Complete remission (CR) and combined CR or CR with partial or incomplete hematologic recovery (CR/CRh/CRi) were secondary efficacy endpoints. The primary analysis was scheduled to occur after 330 deaths had accrued. This prespecified interim analysis for an independent data monitoring committee (DMC) occurred after 248 deaths (75%).
Results
A total of 405 patients were randomized to blinatumomab (n=271) or SOC (n=134) and analyzed for efficacy; 2% and 19%, respectively, elected to receive no study treatment. Baseline characteristics were balanced between treatment groups (blinatumomab, SOC): median age (37y, 37y); median bone marrow blasts (80%, 79%); prior salvage therapy (56%, 52%); and prior alloSCT (35%, 34%). Using results from the DMC analysis, median OS was 7.8 months (95%CI: 5.7, 10.0) for blinatumomab and 4.0 months (95%CI: 2.9, 5.4) for SOC (stratified log-rank test p=.011; hazard ratio=0.71), surpassing the prespecified O’Brien-Fleming boundary p value of 0.0183. Improvement in OS was consistent between subgroups based on age, prior salvage therapy, or prior alloSCT. Response rates were higher for blinatumomab vs SOC, including CR (39% vs 19%; p<.001) and CR/CRh/CRi (46% vs 28%, p=.001). A total of 373 patients received ≥1 dose of blinatumomab (N=266) or SOC (N=107; 47 FLAG ± anthracycline; 19 HiDAC-based; 22 high-dose methotrexate-based; and 19 clofarabine-based) and were analyzed for safety; 57% and 25%, respectively, started at least 2 cycles. Safety outcomes were similar between blinatumomab and SOC (table).Table. Incidence Rates of Adverse Events (AE), Regardless of Causality
Conclusion
This prespecified interim analysis showed that blinatumomab, as compared with SOC chemotherapy, improved the primary endpoint of OS in the phase 3 TOWER study of adults with Ph– r/r BCP-ALL. Remission rates also were higher in the blinatumomab group. AEs in the blinatumomab group were consistent with previous studies. Based on these findings, the DMC recommended stopping the TOWER study for efficacy before the planned final analysis.
Session topic: Presidential Symposium
Keyword(s): B cell acute lymphoblastic leukemia, CD19, Immunotherapy, Survival
Type: Presidential Symposium
Presentation during EHA21: On Friday, June 10, 2016 from 16:35 - 16:47
Location: Hall A1
Background
Blinatumomab, a bispecific T-cell engager antibody construct, binds specifically to CD19 (B cells) and CD3 (T cells) to facilitate lysis of CD19-positive target B-lineage cells. Based on a single-arm phase 2 study, blinatumomab received approvals in the US (accelerated) and EU (conditional) for the treatment of Philadelphia chromosome-negative (Ph–) relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Aims
This phase 3, randomized, open-label study investigated the effect of blinatumomab on overall survival (OS) compared with standard of care (SOC) chemotherapy in adult patients with Ph– r/r BCP-ALL.
Methods
Patients with r/r BCP-ALL (if first relapse, within 1 y) were randomized 2:1 to receive either blinatumomab or SOC chemotherapy (investigator's choice of 1 of 4 defined regimens). Randomization was stratified by age, prior salvage therapy, and prior allogeneic stem cell transplant (alloSCT). Blinatumomab was given in 6-week cycles of 4 weeks on (continuous infusion of 9 µg/d in week 1 of cycle 1, then 28 µg/d) and 2 weeks off; dexamethasone was given pre-dose to prevent cytokine release syndrome. Patients in remission after 2 induction cycles were eligible to continue therapy until relapse. OS was the primary efficacy endpoint. Complete remission (CR) and combined CR or CR with partial or incomplete hematologic recovery (CR/CRh/CRi) were secondary efficacy endpoints. The primary analysis was scheduled to occur after 330 deaths had accrued. This prespecified interim analysis for an independent data monitoring committee (DMC) occurred after 248 deaths (75%).
Results
A total of 405 patients were randomized to blinatumomab (n=271) or SOC (n=134) and analyzed for efficacy; 2% and 19%, respectively, elected to receive no study treatment. Baseline characteristics were balanced between treatment groups (blinatumomab, SOC): median age (37y, 37y); median bone marrow blasts (80%, 79%); prior salvage therapy (56%, 52%); and prior alloSCT (35%, 34%). Using results from the DMC analysis, median OS was 7.8 months (95%CI: 5.7, 10.0) for blinatumomab and 4.0 months (95%CI: 2.9, 5.4) for SOC (stratified log-rank test p=.011; hazard ratio=0.71), surpassing the prespecified O’Brien-Fleming boundary p value of 0.0183. Improvement in OS was consistent between subgroups based on age, prior salvage therapy, or prior alloSCT. Response rates were higher for blinatumomab vs SOC, including CR (39% vs 19%; p<.001) and CR/CRh/CRi (46% vs 28%, p=.001). A total of 373 patients received ≥1 dose of blinatumomab (N=266) or SOC (N=107; 47 FLAG ± anthracycline; 19 HiDAC-based; 22 high-dose methotrexate-based; and 19 clofarabine-based) and were analyzed for safety; 57% and 25%, respectively, started at least 2 cycles. Safety outcomes were similar between blinatumomab and SOC (table).Table. Incidence Rates of Adverse Events (AE), Regardless of Causality
| Blinatumomab (N=266) | SOC (N=107) | |
| Any AE, % (per 100 patient-months) Any grade 3 AE, % Any grade 4 AE, % Any grade 5/fatal AE, % Grade 5 infection, % | 99% (631.3)38%29%19%11% | 99% (764.4)34%40%19%12% |
| Any serious AE, % (per 100 patient-months) Infection, % Blood/lymphatic, % Nervous system, % Cytokine release syndrome, % | 62% (26.4)28%14%7%3% | 45% (38.1)31%16%3%0% |
Conclusion
This prespecified interim analysis showed that blinatumomab, as compared with SOC chemotherapy, improved the primary endpoint of OS in the phase 3 TOWER study of adults with Ph– r/r BCP-ALL. Remission rates also were higher in the blinatumomab group. AEs in the blinatumomab group were consistent with previous studies. Based on these findings, the DMC recommended stopping the TOWER study for efficacy before the planned final analysis.
Session topic: Presidential Symposium
Keyword(s): B cell acute lymphoblastic leukemia, CD19, Immunotherapy, Survival
Abstract: S149
Type: Presidential Symposium
Presentation during EHA21: On Friday, June 10, 2016 from 16:35 - 16:47
Location: Hall A1
Background
Blinatumomab, a bispecific T-cell engager antibody construct, binds specifically to CD19 (B cells) and CD3 (T cells) to facilitate lysis of CD19-positive target B-lineage cells. Based on a single-arm phase 2 study, blinatumomab received approvals in the US (accelerated) and EU (conditional) for the treatment of Philadelphia chromosome-negative (Ph–) relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Aims
This phase 3, randomized, open-label study investigated the effect of blinatumomab on overall survival (OS) compared with standard of care (SOC) chemotherapy in adult patients with Ph– r/r BCP-ALL.
Methods
Patients with r/r BCP-ALL (if first relapse, within 1 y) were randomized 2:1 to receive either blinatumomab or SOC chemotherapy (investigator's choice of 1 of 4 defined regimens). Randomization was stratified by age, prior salvage therapy, and prior allogeneic stem cell transplant (alloSCT). Blinatumomab was given in 6-week cycles of 4 weeks on (continuous infusion of 9 µg/d in week 1 of cycle 1, then 28 µg/d) and 2 weeks off; dexamethasone was given pre-dose to prevent cytokine release syndrome. Patients in remission after 2 induction cycles were eligible to continue therapy until relapse. OS was the primary efficacy endpoint. Complete remission (CR) and combined CR or CR with partial or incomplete hematologic recovery (CR/CRh/CRi) were secondary efficacy endpoints. The primary analysis was scheduled to occur after 330 deaths had accrued. This prespecified interim analysis for an independent data monitoring committee (DMC) occurred after 248 deaths (75%).
Results
A total of 405 patients were randomized to blinatumomab (n=271) or SOC (n=134) and analyzed for efficacy; 2% and 19%, respectively, elected to receive no study treatment. Baseline characteristics were balanced between treatment groups (blinatumomab, SOC): median age (37y, 37y); median bone marrow blasts (80%, 79%); prior salvage therapy (56%, 52%); and prior alloSCT (35%, 34%). Using results from the DMC analysis, median OS was 7.8 months (95%CI: 5.7, 10.0) for blinatumomab and 4.0 months (95%CI: 2.9, 5.4) for SOC (stratified log-rank test p=.011; hazard ratio=0.71), surpassing the prespecified O’Brien-Fleming boundary p value of 0.0183. Improvement in OS was consistent between subgroups based on age, prior salvage therapy, or prior alloSCT. Response rates were higher for blinatumomab vs SOC, including CR (39% vs 19%; p<.001) and CR/CRh/CRi (46% vs 28%, p=.001). A total of 373 patients received ≥1 dose of blinatumomab (N=266) or SOC (N=107; 47 FLAG ± anthracycline; 19 HiDAC-based; 22 high-dose methotrexate-based; and 19 clofarabine-based) and were analyzed for safety; 57% and 25%, respectively, started at least 2 cycles. Safety outcomes were similar between blinatumomab and SOC (table).Table. Incidence Rates of Adverse Events (AE), Regardless of Causality
Conclusion
This prespecified interim analysis showed that blinatumomab, as compared with SOC chemotherapy, improved the primary endpoint of OS in the phase 3 TOWER study of adults with Ph– r/r BCP-ALL. Remission rates also were higher in the blinatumomab group. AEs in the blinatumomab group were consistent with previous studies. Based on these findings, the DMC recommended stopping the TOWER study for efficacy before the planned final analysis.
Session topic: Presidential Symposium
Keyword(s): B cell acute lymphoblastic leukemia, CD19, Immunotherapy, Survival
Type: Presidential Symposium
Presentation during EHA21: On Friday, June 10, 2016 from 16:35 - 16:47
Location: Hall A1
Background
Blinatumomab, a bispecific T-cell engager antibody construct, binds specifically to CD19 (B cells) and CD3 (T cells) to facilitate lysis of CD19-positive target B-lineage cells. Based on a single-arm phase 2 study, blinatumomab received approvals in the US (accelerated) and EU (conditional) for the treatment of Philadelphia chromosome-negative (Ph–) relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Aims
This phase 3, randomized, open-label study investigated the effect of blinatumomab on overall survival (OS) compared with standard of care (SOC) chemotherapy in adult patients with Ph– r/r BCP-ALL.
Methods
Patients with r/r BCP-ALL (if first relapse, within 1 y) were randomized 2:1 to receive either blinatumomab or SOC chemotherapy (investigator's choice of 1 of 4 defined regimens). Randomization was stratified by age, prior salvage therapy, and prior allogeneic stem cell transplant (alloSCT). Blinatumomab was given in 6-week cycles of 4 weeks on (continuous infusion of 9 µg/d in week 1 of cycle 1, then 28 µg/d) and 2 weeks off; dexamethasone was given pre-dose to prevent cytokine release syndrome. Patients in remission after 2 induction cycles were eligible to continue therapy until relapse. OS was the primary efficacy endpoint. Complete remission (CR) and combined CR or CR with partial or incomplete hematologic recovery (CR/CRh/CRi) were secondary efficacy endpoints. The primary analysis was scheduled to occur after 330 deaths had accrued. This prespecified interim analysis for an independent data monitoring committee (DMC) occurred after 248 deaths (75%).
Results
A total of 405 patients were randomized to blinatumomab (n=271) or SOC (n=134) and analyzed for efficacy; 2% and 19%, respectively, elected to receive no study treatment. Baseline characteristics were balanced between treatment groups (blinatumomab, SOC): median age (37y, 37y); median bone marrow blasts (80%, 79%); prior salvage therapy (56%, 52%); and prior alloSCT (35%, 34%). Using results from the DMC analysis, median OS was 7.8 months (95%CI: 5.7, 10.0) for blinatumomab and 4.0 months (95%CI: 2.9, 5.4) for SOC (stratified log-rank test p=.011; hazard ratio=0.71), surpassing the prespecified O’Brien-Fleming boundary p value of 0.0183. Improvement in OS was consistent between subgroups based on age, prior salvage therapy, or prior alloSCT. Response rates were higher for blinatumomab vs SOC, including CR (39% vs 19%; p<.001) and CR/CRh/CRi (46% vs 28%, p=.001). A total of 373 patients received ≥1 dose of blinatumomab (N=266) or SOC (N=107; 47 FLAG ± anthracycline; 19 HiDAC-based; 22 high-dose methotrexate-based; and 19 clofarabine-based) and were analyzed for safety; 57% and 25%, respectively, started at least 2 cycles. Safety outcomes were similar between blinatumomab and SOC (table).Table. Incidence Rates of Adverse Events (AE), Regardless of Causality
| Blinatumomab (N=266) | SOC (N=107) | |
| Any AE, % (per 100 patient-months) Any grade 3 AE, % Any grade 4 AE, % Any grade 5/fatal AE, % Grade 5 infection, % | 99% (631.3)38%29%19%11% | 99% (764.4)34%40%19%12% |
| Any serious AE, % (per 100 patient-months) Infection, % Blood/lymphatic, % Nervous system, % Cytokine release syndrome, % | 62% (26.4)28%14%7%3% | 45% (38.1)31%16%3%0% |
Conclusion
This prespecified interim analysis showed that blinatumomab, as compared with SOC chemotherapy, improved the primary endpoint of OS in the phase 3 TOWER study of adults with Ph– r/r BCP-ALL. Remission rates also were higher in the blinatumomab group. AEs in the blinatumomab group were consistent with previous studies. Based on these findings, the DMC recommended stopping the TOWER study for efficacy before the planned final analysis.
Session topic: Presidential Symposium
Keyword(s): B cell acute lymphoblastic leukemia, CD19, Immunotherapy, Survival
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