Anas Younes, MD, Chief of the Lymphoma Service at Memorial Sloan-Kettering Cancer Center in New York, told The ASCO Post, “Of the 800 or so ALK-positive anaplastic large-cell lymphoma patients in the United States, 70% to 80% are cured by CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone]. In the remaining 20% to 30%, second-line therapy with autologous stem cell transplant consolidation cures another 50%. Then brentuximab vedotin [Adcetris] can be used in the remaining patients. Crizotinib ­[Xalkori] may be effective in patients who have not responded to other therapies such as brentuximab,” he said.

Noteworthy Mechanism

Dr. Younes said the excitement over this study relates to the ability to target the oncogenic driver of anaplastic large-cell lymphoma—the ALK gene translocation—as opposed to brentuximab, which delivers a chemotherapy-like agent to CD30-expressing lymphomas.

“Crizotinib has good activity and safety. The challenge is how to move crizotinib forward in a relatively rare disease with a high cure rate on currently available regimens. You would need a huge randomized trial to compare CHOP vs CHOP plus crizotinib in newly diagnosed patients. An alternative, more efficient strategy would be to use this drug in brentuximab failures, or perhaps combine it with brentuximab,” Dr. Younes stated. ■

Disclosure: Dr. Younes reported no potential conflicts of interest.