Expert Point of View: Amir T. Fathi, MD

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For years, adults with acute lymphoblastic leukemia (ALL) have been treated with intensive, multiagent, cytotoxic chemotherapy involving multiple rounds of treatment, derived from regimens that are highly effective in children. Although the survival of children with ALL hovers around 90%, less than 50% of adults have long-term survival with this approach, and many experience relapsed disease, explained Amir T. Fathi, MD, Instructor of Medicine and Medical Oncology at Dana-Farber/Harvard Cancer Center and Massachusetts General Hospital in Boston.

“Therefore, there has been an urgent need for new treatments for adults with ALL. Novel and targeted therapies are now emerging that appear to be highly effective. The investigational antibody-drug conjugates are antibody-based therapies that hold promise for treatment of ALL in adults. Studies have shown impressive rates of response with single-agent therapy in those with relapsed /refractory ALL,” Dr. Fathi stated.

Novel Mechanisms

“Inotuzumab is an anti-CD22 humanized antibody-drug conjugate with significant response rare in relapsed/refractory ALL, and is among a growing list of targeted therapies that mediate their effect through an immunologic mechanism,” he continued. “Another novel and targeted agent, blinotumumab, belonging to a class of compounds called bi-specific T-cell engagers (BiTE), has also demonstrated significant promise in results from phase II studies,” he added.

“These drugs use novel mechanisms to attack lymphoblasts in ALL by targeting proteins on the surface of these cells. I suspect that such targeted agents will become an integral part of therapy for adults with ALL in the near future, which is great news for our patients who are in need of more effective therapies. Nevertheless, we will need additional data and advanced phase studies to further assess clinical benefit in this population of patients with high-risk ALL, and these studies are ongoing,” Dr. Fathi said. n

Disclosure: Dr. Fathi has served in an advisory capacity for Seattle Genetics.

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