Blinatumomab vs historic standard-of-care treatment for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukaemia

Abstract

Objectives: Survival outcomes from a single-arm phase 2 blinatumomab study in patients with minimal residual disease (MRD)-positive B-cell precursor (BCP)-acute lymphoblastic leukaemia (ALL) were compared with those receiving standard of care (SOC) in a historic data set.

Methods: The primary analysis comprised adult Philadelphia chromosome (Ph)-negative patients in first complete haematologic remission (MRD ≥ 10-3 ). Relapse-free survival (RFS) and overall survival (OS) were compared between blinatumomab- and SOC-treatment groups. Baseline differences between groups were adjusted by propensity scores.

Results: The primary analysis included 73 and 182 patients from the blinatumomab and historic data sets, respectively. When weighted by age to the blinatumomab-treatment group, median RFS was 7.8 months and median OS was 25.9 months in the SOC-treated group. In the blinatumomab study, median RFS was 35.2 months; median OS was not evaluable. Propensity score weighting achieved balance with seven baseline prognostic factors. With adjustment for haematopoietic stem cell transplantation (HSCT) status, a 50% reduction in risk of relapse or death was observed with blinatumomab vs SOC. Median RFS, unadjusted for HSCT status, was 35.2 months with blinatumomab and 8.3 months with SOC.

Conclusions: These analyses suggest that blinatumomab improves RFS, and possibly OS, in adults with MRD-positive Ph-negative BCP-ALL vs SOC.

Keywords: acute lymphoblastic leukaemia; clinical trials.

Conflict of interest statement

NG has received honoraria and research funding and has served on advisory boards, for Amgen, Pfizer, Celgene and Novartis; HD has received honoraria and/or research funding from Amgen, Agios, Seattle Genetics, Celgene, Sunesis, Roche, Pfizer, Ambit‐Daiichi Sankyo, Shire‐Baxalta, Ariad‐Incyte, Karyopharm, Abbvie, Novartis, Kite, Otsuka, Celator‐Jazz, Astellas, Menarini, Cellectis, Janssen, ImmunoGen and Servier; SG has received honoraria and has served on advisory boards for Amgen; MB has received honoraria and has served on advisory boards and at Speaker Bureaus for Amgen, Hoffman‐La Roche and Incyte, and has received grant/research support from Affimed Therapeutics, Amgen Research, Celgene and Regeneron; MD has received honoraria and/or research funding from AbbVie, Amgen, AOP Orphan, Gilead, Janssen‐Cilag, Novartis and Roche; RF has served on advisory boards and at Speaker Bureaus for Janssen, AbbVie, Celgene, Novartis, Amgen, Pfizer and Servier; DH declares no conflicts of interest; CK, MS, CT and GZ are employees and stockholders of Amgen; GM has served as an adviser to Amgen, Ariad/Incyte, Pfizer, Roche, Celgene, Janssen and Jazz Pharmaceuticals, and on Speaker Bureaus for Novartis, Pfizer and Celgene, and has received travel compensation from Daiichi Sankyo, Roche and Shire; EP has received research funds from Abbvie, Roche, Amgen, Novartis and Bristol; JMR has received honoraria and research funds and has served on advisory boards, for Amgen, Pfizer, Shire and Ariad; RB has received honoraria and has served on advisory boards for Amgen, Pfizer, Shire and Incyte.

© 2019 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.

Figures

Figure 1

Kaplan‐Meier curve of relapse‐free survival for the primary analysis set after propensity score adjustment using stabilised inverse probability of treatment weighting. CI, confidence interval; HR, hazard ratio; NE, not evaluable; RFS, relapse‐free survival; SOC, standard of care

Figure 2

Kaplan‐Meier curve of overall survival for the primary analysis set after propensity score adjustment using stabilised inverse probability of treatment weighting. CI, confidence interval; HR, hazard ratio; NE, not evaluable; OS, overall survival; SOC, standard of care