The FDA announced Breakthrough Therapy Designation (BTD) for acalabrutinib (Calquence) as a single agent to treat chronic lymphocytic leukemia (CLL)
Dr. Rick Furman of the CLL Society Scientific Advisory Board helps explain the recent warning about idelalisib and provides us with some context and perspective. As he says: The FDAs goal with these warnings is not to eliminate idelalisib use, but to make sure the physicians and patients take these data into account when making an informed treatment decision.
This new warning is based upon data from three idelalisib studies (GS-US-312-0123/0124/0125) which were testing idelalisib in combination with bendamustine plus rituximab or rituximab alone in CLL and indolent NHL (non-Hodgkin’s lymphoma). These studies were testing idelalisib in less heavily treated patients or treatment-naïve patients. The data analyzed in aggregate from these three studies demonstrated an increase in risk of death with idelalisib treatment, generally due to a higher rate of infectious deaths, including sepsis, febrile neutropenia (fever with low neutrophil count), Pneumocystis pneumonia (PCP), and CMV (cytomegalovirus) infections.
One hypothesis behind why this safety signal might not have been seen in earlier studies relates to the relatively good prognosis of patients in this study, compared with the earlier studies. This could translate into patients succumbing to infections more frequently in the control arms due to the amount of prior therapy or physicians being more aggressive with prophylaxis and monitoring given the amount of prior treatment the patients had received and preventing more infections in the earlier studies.
The FDAs goal with these warnings is not to eliminate idelalisib use, but to make sure the physicians and patients take these data into account when making an informed treatment decision. For those patients going on idelalisib treatment, there are also specific recommendations to help lessen the risks.
- First, patients should receive PCP prophylaxis (Bactrim, dapsone, or atovoquone).
- Second, patients should have monthly CMV monitoring.
It is also important to remember that for those patients who are currently on idelalisib and doing well, discontinuing idelalisib is an option, but I always hesitate to interrupt an agent that is working.
March 28, 2016
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