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Adv Ther. 2019 Aug;36(8):2147-2160. doi: 10.1007/s12325-019-00991-w. Epub 2019 May 28.

Indirect Treatment Comparison of Inotuzumab Ozogamicin Versus Blinatumomab for Relapsed or Refractory Acute Lymphoblastic Leukemia.

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Evidera, St-Laurent, QC, Canada.
Pfizer Inc, New York, NY, USA.
Evidera, Waltham, MA, USA.
Pfizer Inc, Cambridge, MA, USA.
Evidera, St-Laurent, QC, Canada.
Pfizer Inc, Groton, CT, USA.
University Hospital, Münster, Germany.



No head-to-head studies have compared inotuzumab ozogamicin (InO) and blinatumomab (Blina) for the treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). Indirect treatment comparisons (ITCs), namely network meta-analysis (NMA), anchored matching-adjusted indirect comparison (MAIC), and simulated treatment comparison (STC), were conducted to compare the relative efficacy of these therapies.


Patient-level data from a study that evaluated InO with standard of care (SoC) chemotherapy (INO-VATE-ALL) and published data from a study that evaluated Blina with SoC chemotherapy (TOWER) were used in the analyses. Endpoints evaluated included remission rate defined as complete remission or complete remission with incomplete hematologic recovery (CR/CRi), hematopoietic stem cell transplantation (HSCT), overall survival (OS), and event-free survival (EFS). For each outcome, treatment-effect modifiers were adjusted for in the anchored MAIC and STC analyses.


Analyses showed statistically significant higher rates of remission and HSCT with InO compared to Blina irrespective of the ITC method used or measure of the effect (i.e., odds ratio [OR] or rate difference). The treatment effects derived from the MAIC and STC analyses were consistent and stronger than those estimated from the NMA. A trend favoring InO was detected for EFS. The ITC results for OS suggest no difference between InO and Blina.


Results from these ITCs indicated a statistically significant advantage for InO over Blina for rates of remission and HSCT in adults with relapsed or refractory B cell precursor ALL. It was not possible to fully adjust for all treatment-effect modifiers, and the similarity in chemotherapy regimens used in the SoC comparator arms of the INO-VATE-ALL and TOWER studies is worthy of further exploration. Both studies, however, used chemotherapy regimens that have a low response rate; therefore, no significant differences in efficacy outcomes are expected between SoC arms.


Pfizer Inc, New York, NY. Plain language summary available for this article.


Blinatumomab; Indirect treatment comparison; Inotuzumab ozogamicin; Matching-adjusted indirect comparison; Relapsed or refractory acute lymphoblastic leukemia; Simulated treatment comparison


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