Inotuzumab Ozogamicin with Bosutinib for Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia or Lymphoid Blast Phase of Chronic Myeloid Leukemia.

Relapsed/refractory (R/R) Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) and lymphoid blast phase of chronic myeloid leukemia (LBP-CML) have poor outcomes. We designed a phase 1/2 study combining inotuzumab ozogamicin with bosutinib for this patient population. Patients with T315I mutation were excluded. Bosutinib was administered daily at three dose levels (300mg/d, 400mg/d, 500mg/d) in a 3+3 design. Inotuzumab ozogamicin was dosed weekly during cycle 1, and once every 4 weeks subsequently for total 6 cycles. The primary objective was to determine the safety and the maximum tolerated dose (MTD) of bosutinib in combination with inotuzumab ozogamicin. Eighteen patients were enrolled (Ph-positive ALL, n=16; LBP-CML, n=2). The median age was 62 years (range, 19-74) and the median number of prior therapies was 1 (range, 1-5). Dose limiting toxicities included grade 3 skin rash and bosutinib 400 mg daily was determined as the MTD. The most frequent grade 3/4 treatment-emergent adverse events were thrombocytopenia (60%) and neutropenia (38%). A complete response (CR) / CR with incomplete count recovery (CRi) was achieved in 15/18 (83%) patients; 11/18 (61%) patients achieved negative measurable residual disease by flow cytometry. Complete molecular response was noted in 10/18 (56%) patients. The 30-day mortality was 0%. After a median follow-up of 44 months, the median duration of response and overall survival were 7.7 months and 13.5 months, respectively. Six patients had a subsequent allogeneic stem cell transplant. No patient developed veno-occlusive disease. Inotuzumab ozogamicin with bosutinib was well tolerated in R/R Ph-positive ALL and LBP-CML. This article is protected by copyright. All rights reserved.

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Authors: Nitin Jain, Abhishek Maiti, Farhad Ravandi, Marina Konopleva, Naval Daver, Tapan Kadia, Naveen Pemmaraju, Nicholas Short, Partow Kebriaei, Jing Ning, Jorge Cortes, Elias Jabbour, Hagop Kantarjian