At 2PM today, our article entitled "Idelalisib and Rituximab in Relapsed CLL" was posted to the New England Journal of Medicine webpage. I blogged about "the race tightens" last October after a press release suggested this would be an important data set. Press releases, abstracts, ASH presentations are important, but nothing matches the importance of the full manuscript. The full article can be accessed here.
This study took patients who were considered inappropriate for traditional chemotherapy on the basis of bad kidney function (main way we get rid of fludarabine), poor marrow function, or lots of other medical conditions. It then randomized patients to either rituximab or rituximab in combination with idelalisib - one of the new BCR signal inhibitors.
Critics have argued that rituximab is considered inappropriate care for patients with CLL. In general I agree, but I think this study worked very hard to identify patients for whom this treatment might be appropriate. NCCN guidelines list rituximab as an appropriate therapy for patients with lots of medical problems. Patterns of care data sets indicate that it is commonly used in North America. Ofatumumab is another CD20 antibody that is approved for single agent (and our rituximab control arm did almost as well as ofatumumab in the study that led to its approval). You can argue this point endlessly but FDA standards point toward "commonly accepted standard" and I think you can make an argument that rituximab may be appropriate in selected circumstances and this trial worked hard to define when that might be.
Long story short - adding idelalisib to rituximab absolutely blows away rituximab alone.
The overall response rate >90% versus 4%, progression free survival and even OVERALL SURVIVAL favor the addition of idelalisib. Very few studies in CLL have EVER shown improvement in overall survival. In fact, we were not even trying to show that point in the study and were somewhat surprised the difference was so large. The data set also shows the relative ineffectiveness of rituximab when administered alone in previously treated CLL patients (improves WBC for 4-6 months, nodes shrink a little, then disease takes off).
This study will hopefully pave the way for idelalisib to be approved in CLL sometime in 2014. The drug has been granted "breakthrough" designation by the FDA for CLL and has a 9/11/14 decision date by the FDA in non hodgkins lymphoma