Safety and Efficacy of Blinatumomab in Combination With a Tyrosine Kinase Inhibitor for the Treatment of Relapsed Philadelphia Chromosome-positive Leukemia.

Abstract

OBJECTIVE:

The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy.

PATIENTS AND METHODS:

We retrospectively studied 12 adults with relapsed/refractory Ph+ acute lymphoblastic leukemia (n = 9) and chronic myeloid leukemia in blast crisis (n = 3), treated with the combination blinatumomab and a TKI (ponatinib, n = 8; dasatinib, n = 3; bosutinib, n = 1). All patients have previously failed at least 1 line of chemotherapy, including allogeneic stem cell transplantation, and 1 class of TKIs. Patients were treated for either overt hematologic relapse (n = 6) or persistent minimal residual disease following other regimens (n = 6).

RESULTS:

The complete hematologic, cytogenetic, and molecular response rates were 50% (3/6), 71% (5/7), and 75% (9/12), respectively. Two cases of grade 2 cytokine release syndrome were observed, all of which resolved with steroids and tocilizumab. No cardiovascular adverse events were encountered. With a median follow-up of 8 months, the median survival was not reached; the 6-month and 1-year overall survival rates were 73%.

CONCLUSIONS:

The combination of blinatumomab with TKI is safe and effective in patients with relapsed/refractory Ph+ disease. Prospective studies are warranted.

• Authors: Rita Assi, Hagop Kantarjian, Nicholas J Short, Naval Daver, Koichi Takahashi, Guillermo Garcia-Manero, Courtney DiNardo, Jan Burger, Jorge Cortes, Nitin Jain, William Wierda, Salim Chamoun, Marina Konopleva, Elias Jabbour
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 17 Issue 12 Pg. 897-901 (Dec 2017) ISSN: 2152-2669 [Electronic] United States
• PMID: 28927784 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Bispecific
• Protein Kinase Inhibitors
• blinatumomab
• Fusion Proteins, bcr-abl

Topics

• Adult
• Aged
• Antibodies, Bispecific (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Drug Resistance, Neoplasm
• Fusion Proteins, bcr-abl (genetics)
• Humans
• Kaplan-Meier Estimate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics)
• Middle Aged
• Neoplasm Recurrence, Local
• Protein Kinase Inhibitors (administration & dosage)
• Retrospective Studies
• Treatment Outcome