Dr Dreyling, MD, PhD, professor of medicine at the University of Munich Hospital in Germany, is a renowned hematologist with expertise in lymphoma. In this question-and-answer session, Dr Dreyling discusses research presented at the 2017 American Society of Hematology (ASH) Annual Meeting likely to have a clinical impact among patients with NHL.
Cancer Therapy Advisor (CTA): Please explain the rationale for conducting the CHRONOS-1 trial. What pre-clinical evidence suggested that copanlisib would be effective in B cell non-Hodgkin lymphomas?
Dr Dreyling: The first 2 treatment lines in follicular lymphoma (FL) are rather well-established (combination of rituximab with either CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone] or bendamustine), but when it comes to the third line, the treatment landscape was wide open.
Based on the international ESMO [European Society for Medical Oncology] guidelines, monotherapy in the third line is the standard of care and, in my opinion, PI3K inhibition is the most effective targeted treatment approach in FL. While it is well-known that the delta isoform is exclusively expressed in leukocytes, it is less broadly realized that leukocytes express other isoforms, especially alpha and gamma.
In fact, based on sequential analysis in chronic lymphocytic leukemia and mantle cell lymphoma, expression of the alpha isoform has been recognized as a mechanism of resistance in relapsed disease. Copanlisib is a PI3K inhibitor with inhibitory activity predominantly against the PI3K-alpha and PI3K-delta isoforms expressed in malignant B cells. This was the rationale for conducting the CHRONOS-1 trial.
CTA: The updated analysis presented at ASH suggests a median duration of response (DOR) of 12.2 months, which contrasts with the 20-month DOR noted at the primary evaluation. Can you discuss this discrepancy?
Dr Dreyling: The median duration of 12.2 months refer to the FL subset, whereas in the total group (including the more responsive marginal zone lymphoma with ongoing remissions of 80% up to 2 years) median duration is in the range of more than 1 and a half years.
When considering these parameters, it is important to note that the ongoing remission rate remained in the range of 50% plus or minus 5% after a year and a half.