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. 2020 Jan 15;126(2):304-310.
doi: 10.1002/cncr.32558. Epub 2019 Oct 18.

Blinatumomab Compared With Standard of Care for the Treatment of Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-precursor Acute Lymphoblastic Leukemia

Free PMC article

Blinatumomab Compared With Standard of Care for the Treatment of Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-precursor Acute Lymphoblastic Leukemia

Alessandro Rambaldi et al. Cancer. .
Free PMC article


Background: A single-arm, phase 2 trial demonstrated the efficacy and safety of blinatumomab, a bispecific T-cell-engaging antibody construct, in patients with relapsed/refractory (r/r) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), a rare hematologic malignancy with limited treatment options. This study compared outcomes with blinatumomab with those of a historical control treated with the standard of care (SOC).

Methods: The blinatumomab trial enrolled adult patients with Ph+ ALL who were r/r to at least 1 second-generation tyrosine kinase inhibitor (n = 45). Propensity score analysis (PSA) was used to compare outcomes with blinatumomab with those of an external cohort of similar patients receiving SOC chemotherapy (n = 55). The PSA mitigated confounding variables between studies by adjusting for imbalances in the age at diagnosis and start of treatment, sex, duration from diagnosis to most recent treatment, prior allogeneic hematopoietic stem cell transplantation, prior salvage therapy, and number of salvage therapies. Bayesian data augmentation was applied to improve power to 80% with data from a phase 3 blinatumomab study in r/r Philadelphia chromosome-negative ALL.

Results: In the PSA, the rate of complete remission or complete remission with partial hematologic recovery was 36% for blinatumomab and 25% for SOC, and this resulted in an odds ratio of 1.54 (95% confidence interval [CI], 0.61-3.89) or 1.70 (95% credible interval [CrI], 0.94-2.94) with Bayesian data augmentation. Overall survival favored blinatumomab over SOC, with a hazard ratio of 0.81 (95% CI, 0.57-1.14) or 0.77 (95% CrI, 0.61-0.96) with Bayesian data augmentation.

Conclusions: These results further support blinatumomab as a treatment option for patients with r/r Ph+ ALL.

Keywords: Philadelphia chromosome-positive acute lymphoblastic leukemia; blinatumomab; propensity score analysis; remission; standard of care; survival.

Conflict of interest statement

Alessandro Rambaldi reports consultancy for and travel support from Amgen, Pfizer, Roche, Celgene, Novartis, Italfarmaco, Gilead, and Omeros. Josep‐Maria Ribera reports consultancy for, travel support from, and grants from Amgen, Pfizer, Celgene, Novartis, Jazz Pharmaceuticals, Shire, and Takeda. Hagop M. Kantarjian reports honoraria and/or research funding from Agios, Daiichi‐Sankyo, Cyclacel, Jazz Pharma, Novartis, Astex, AbbVie, Orsenix, Immunogen, Actinium, Delta‐Fly Pharma, ARIAD Pharmaceuticals, Bristol‐Meyers Squibb, Pfizer, Takeda, and Amgen. Hervé Dombret reports honoraria and/or research funding from Amgen, Agios, Ceylad, 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. Oliver G. Ottmann reports consultancy for Amgen, Novartis, Incyte, Takeda, Celgene, Fusion Pharma, Pfizer, and Roche; research support from Incyte and Celgene; and travel support from Amgen, Novartis, and Incyte. Anthony S. Stein reports work on speakers bureaus for Amgen, Stemline, and Celgene. Catherine A. Tuglus reports employment by and stock holdings in Amgen. Xiaoyue Zhao reports employment by Amgen. Christopher Kim reports employment by and stock holdings in Amgen. Giovanni Martinelli reports work as an advisor to Amgen, Ariad/Incyte, Pfizer, Roche, Celgene, Janssen, and Jazz Pharmaceuticals; work on speakers bureaus for Novartis, Pfizer, and Celgene; personal fees from AbbVie; and travel compensation from Daiichi Sankyo, Roche, and Shire.


Figure 1
Figure 1
Cox proportional hazards model estimates of survival by treatment (A) with and (B) without Bayesian data augmentation (80% power). IPTW‐ATE adjustments were made. Survival estimates were calculated with the proportion of prior hematopoietic stem cell transplantation: 0.327 for the control group and 0.4 for the blinatumomab group. ATE indicates average treatment effect; CI, confidence interval; CrI, credible interval; HR, hazard ratio; IPTW, inverse probability of treatment weighting; SOC, standard of care.

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