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.

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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.