Inotuzumab ozogamicin with bosutinib for relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia or lymphoid blast phase of chronic myeloid leukemia.

Abstract

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 (300 mg/d, 400 mg/d, 500 mg/d) in a 3 + 3 design. Inotuzumab ozogamicin was dosed weekly during cycle one, and once every 4 weeks subsequently for a total of six 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 one (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.

• 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
• Journal: American journal of hematology (Am J Hematol) Vol. 96 Issue 8 Pg. 1000-1007 (08 01 2021) ISSN: 1096-8652 [Electronic] United States
• PMID: 33991360 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

• Aniline Compounds
• Nitriles
• Quinolines
• bosutinib
• Inotuzumab Ozogamicin

Topics

• Adult
• Aged
• Aniline Compounds (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Blast Crisis (drug therapy)
• Female
• Humans
• Inotuzumab Ozogamicin (pharmacology, therapeutic use)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy)
• Male
• Middle Aged
• Nitriles (pharmacology, therapeutic use)
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)
• Quinolines (pharmacology, therapeutic use)
• Young Adult