BLINATUMOMAB FOR MINIMAL RESIDUAL DISEASE (MRD) IN ADULTS WITH B­CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA (BCP­ALL): MEDIAN OVERALL SURVIVAL (OS) NOT REACHED AT 5 YEARS FOR COMPLETE MRD RESPONDERS
Author(s): ,
Nicola Goekbuget
Affiliations:
Dept. of Medicine II,Goethe University Hospital,Frankfurt,Germany
,
Hervé Dombret
Affiliations:
Hematology,University Hôpital Saint­-Louis,Paris,France;Assistance Publique­-Hôpitaux de Paris,Paris,France
,
Gerhard Zugmaier
Affiliations:
Amgen Research (Munich), GmbH,Munich,Germany
,
Massimiliano Bonifacio
Affiliations:
Department of Medicine, Section of Hematology,Verona University,Verona,Italy
,
Carlos Graux
Affiliations:
Université Catholique de Louvain, CHU UCL Namur (Godinne),Yvoir,Belgium
,
Christoph Faul
Affiliations:
University Hospital and Comprehensive Cancer Center Tübingen, Universitätsklinikum Tübingen,Tübingen,Germany
,
Max S. Topp
Affiliations:
Medizinische Klinik und Poliklinik II,Universitätsklinikum Würzburg,Würzburg,Germany
,
Monika Brüggemann
Affiliations:
Klinik für Innere Medizin II,Universitätsklinikum Schleswig­-Holstein,Kiel,Germany
,
Kate Taylor
Affiliations:
Amgen, Ltd.,Cambridge,United Kingdom
Ralf Bargou
Affiliations:
Comprehensive Cancer Center Mainfranken,Uniklinikum Würzburg,Würzburg,Germany
EHA Library. Goekbuget N. 06/16/19; 267373; S1619
Nicola Goekbuget
Nicola Goekbuget
Contributions
Abstract

Abstract: S1619

Type: Oral Presentation

Presentation during EHA24: On Sunday, June 16, 2019 from 08:30 - 08:45

Location: Elicium 1

Background
MRD is the strongest predictor of relapse in BCP-ALL. Blinatumomab is a bispecific immunotherapy that redirects T cells to kill CD19+ target cells. In a single-arm study (BLAST; NCT01207388) in adults with BCP-ALL and MRD, we previously reported that 78% (88/113) of patients achieved a complete MRD response after cycle 1 of blinatumomab. Patient incidences of grade 3 or 4 adverse events, including neurologic events (13%) or cytokine release syndrome (2%), were consistent with previous blinatumomab studies.

Aims
This report describes the final analysis of OS for adults with BCP-ALL and MRD in the BLAST study, with a minimum patient follow-up of 5 years after blinatumomab treatment.

Methods
The BLAST study enrolled adults with BCP-ALL in first (CR1) or subsequent (CR2+) hematologic complete remission after ≥3 intensive chemotherapy blocks, with MRD (≥10–3) at least 2 weeks after the last chemotherapy. All patients received blinatumomab 15 µg/m2per day for up to 4 cycles. Each cycle was 4 weeks of continuous infusion and 2 weeks off. Complete MRD response was defined as no target amplification, with a minimum sensitivity of 10–4. After MRD response assessment (end of cycle 1), patients could undergo allogeneic hematopoietic stem cell transplantation (HSCT) at any time. Kaplan-Meier estimates of OS were determined after long-term follow-up (5 years). A conditional landmark of 45 days (the end of cycle 1) was used for subgroup analyses by complete MRD response. 

Results
Of 116 patients with MRD who received blinatumomab, OS was evaluated for 110 patients with Philadelphia chromosome–negative (Ph) BCP-ALL and <5% blasts at enrollment, including 74 who received HSCT in continuous complete remission (CCR) after blinatumomab. With a median follow-up of 59.8 months, median OS was 36.5 months (95% CI: 22.0-not estimable [NE]). At 5 years, outcomes with vs without HSCT in CCR were as follows: alive without relapse, 40.5% vs 19.4%; relapse, 23.0% vs 72.2%; and death without relapse, 36.5% vs 8.3%. Analyses of OS by complete MRD response in cycle 1 (n=107) excluded patients with no central MRD assay (n=1) or inadequate MRD test sensitivity (n=2). Median OS was not reached (95% CI: 29.5 months-NE) for complete MRD responders (n=84) and 14.4 months (95% CI: 3.8-32.3) for MRD nonresponders (n=23; log-rank p=0.002; Figure 1). Estimated 5-year survival was 43% overall (95% CI: 34%>52%) and 50% for complete MRD responders (95% CI: 39%>60%). Among HSCT recipients in CCR, median OS from HSCT was not reached (95% CI: 25.7 months-NE) for complete MRD responders (n=61) and 16.5 months (95% CI: 1.1-NE) for MRD nonresponders (n=10; log-rank p=0.065). Among patients with MRD in CR1, median OS was not reached (95% CI: 29.5 months-NE) for complete MRD responders (n=60) and 10.6 months (95% CI: 2.7-39.7) for MRD nonresponders (n=13; p=0.008).

Conclusion
In the final, 5-year follow-up analysis of a multinational study of adults with BCP-ALL in hematologic complete remission with MRD, median OS was 36.5 months after blinatumomab treatment. Median OS was not reached among patients with a complete MRD response in cycle 1 of blinatumomab treatment. These results provide further support for long-term OS benefits associated with blinatumomab treatment in adults with BCP-ALL and MRD.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): ALL, Minimal residual disease (MRD), Survival, Transplant

Abstract: S1619

Type: Oral Presentation

Presentation during EHA24: On Sunday, June 16, 2019 from 08:30 - 08:45

Location: Elicium 1

Background
MRD is the strongest predictor of relapse in BCP-ALL. Blinatumomab is a bispecific immunotherapy that redirects T cells to kill CD19+ target cells. In a single-arm study (BLAST; NCT01207388) in adults with BCP-ALL and MRD, we previously reported that 78% (88/113) of patients achieved a complete MRD response after cycle 1 of blinatumomab. Patient incidences of grade 3 or 4 adverse events, including neurologic events (13%) or cytokine release syndrome (2%), were consistent with previous blinatumomab studies.

Aims
This report describes the final analysis of OS for adults with BCP-ALL and MRD in the BLAST study, with a minimum patient follow-up of 5 years after blinatumomab treatment.

Methods
The BLAST study enrolled adults with BCP-ALL in first (CR1) or subsequent (CR2+) hematologic complete remission after ≥3 intensive chemotherapy blocks, with MRD (≥10–3) at least 2 weeks after the last chemotherapy. All patients received blinatumomab 15 µg/m2per day for up to 4 cycles. Each cycle was 4 weeks of continuous infusion and 2 weeks off. Complete MRD response was defined as no target amplification, with a minimum sensitivity of 10–4. After MRD response assessment (end of cycle 1), patients could undergo allogeneic hematopoietic stem cell transplantation (HSCT) at any time. Kaplan-Meier estimates of OS were determined after long-term follow-up (5 years). A conditional landmark of 45 days (the end of cycle 1) was used for subgroup analyses by complete MRD response. 

Results
Of 116 patients with MRD who received blinatumomab, OS was evaluated for 110 patients with Philadelphia chromosome–negative (Ph) BCP-ALL and <5% blasts at enrollment, including 74 who received HSCT in continuous complete remission (CCR) after blinatumomab. With a median follow-up of 59.8 months, median OS was 36.5 months (95% CI: 22.0-not estimable [NE]). At 5 years, outcomes with vs without HSCT in CCR were as follows: alive without relapse, 40.5% vs 19.4%; relapse, 23.0% vs 72.2%; and death without relapse, 36.5% vs 8.3%. Analyses of OS by complete MRD response in cycle 1 (n=107) excluded patients with no central MRD assay (n=1) or inadequate MRD test sensitivity (n=2). Median OS was not reached (95% CI: 29.5 months-NE) for complete MRD responders (n=84) and 14.4 months (95% CI: 3.8-32.3) for MRD nonresponders (n=23; log-rank p=0.002; Figure 1). Estimated 5-year survival was 43% overall (95% CI: 34%>52%) and 50% for complete MRD responders (95% CI: 39%>60%). Among HSCT recipients in CCR, median OS from HSCT was not reached (95% CI: 25.7 months-NE) for complete MRD responders (n=61) and 16.5 months (95% CI: 1.1-NE) for MRD nonresponders (n=10; log-rank p=0.065). Among patients with MRD in CR1, median OS was not reached (95% CI: 29.5 months-NE) for complete MRD responders (n=60) and 10.6 months (95% CI: 2.7-39.7) for MRD nonresponders (n=13; p=0.008).

Conclusion
In the final, 5-year follow-up analysis of a multinational study of adults with BCP-ALL in hematologic complete remission with MRD, median OS was 36.5 months after blinatumomab treatment. Median OS was not reached among patients with a complete MRD response in cycle 1 of blinatumomab treatment. These results provide further support for long-term OS benefits associated with blinatumomab treatment in adults with BCP-ALL and MRD.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): ALL, Minimal residual disease (MRD), Survival, Transplant

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