Among patients with relapsed/refractory acute lymphoblastic leukemia (ALL), those with Philadelphia chromosome (Ph)-positive disease experience a higher rate of relapse and poorer chances of long-term survival. According to results of the phase 3 INO-VATE trial recently published in Cancer, inotuzumab ozogamicin, a humanized anti-CD22 monoclonal antibody, achieved high rates of response, remission, and progression-free survival in patients with this disease. In this interview with i3 Health, Hagop Kantarjian, MD, Chairman of the Department of Leukemia at the University of Texas MD Anderson Cancer Center and the study's principal investigator, discusses the significance of these results and the future of treatment for patients with relapsed/refractory Ph-positive ALL.
What are some of the most challenging aspects of treating patients with relapsed/refractory Ph-positive ALL?
Hagop Kantarjian, MD: Historically, treatment options for relapsed/refractory Ph-positive ALL have been limited.
Can you comment on the significance of your findings regarding inotuzumab ozogamicin in this patient population?
Dr. Kantarjian: In our study, single-agent inotuzumab ozogamicin resulted in high rates of complete remission in patients with relapsed/refractory Ph-positive ALL. This finding paves the way for the development of future therapies combining inotuzumab ozogamicin with BCR-ABL1 tyrosine kinase inhibitors (TKIs)—ponatinib, in particular—and also with chemotherapy and other ALL-targeting antibodies like blinatumomab, both in salvage therapy and, more importantly, in frontline therapy for Ph-positive ALL.
How do you foresee the treatment of relapsed/refractory Ph-positive ALL evolving in the coming years?
Dr. Kantarjian: The future of treatment for this disease will involve combinations of ponatinib with inotuzumab ozogamicin, blinatumomab, and chemotherapy, as well as with allogeneic stem cell transplantation (SCT) and post-SCT maintenance. The aim of these developments is a curative intent in a disease which was historically incurable.
Do you have any words of advice for members of the cancer care team treating patients with relapsed/refractory Ph-positive ALL?
Dr. Kantarjian: There is a need for us to move rapidly from single-agent therapy to potentially curative combinations. Patients with this disease should be referred to leukemia cancer centers as soon as possible to be treated on protocols, rather than being treated in community practice.
About Dr. Kantarjian
Hagop Kantarjian, MD, is the Chairman of the Department of Leukemia and the Samsung Distinguished University Chair in Cancer Medicine at the University of Texas MD Anderson Cancer Center. He specializes in the treatment of patients with hematological malignancies, including chronic myeloid leukemia, myelodysplastic syndromes, and ALL. Dr. Kantarjian's research focuses on the development of novel therapeutics for patients with leukemia, and his work has been instrumental in the FDA approvals of more than 20 agents. He has authored or coauthored over 1,800 publications in peer-reviewed journals.
For More Information
Stock W, Martinelli G, Stelljes M, et al (2020). Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome-positive relapsed/refractory acute lymphoblastic leukemia. Cancer. [Epub ahead of print] DOI:10.1002/cncr.33321
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.