Idelalisib Combo Rings Bells in Relapsed CLL

Bruce D. Cheson, MD


February 04, 2014

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Hello. This is Bruce Cheson from Georgetown University Hospital, Lombardi Comprehensive Cancer Center, speaking to you for Medscape Hematology.

As most of you are aware, the world is changing for the treatment of patients with chronic lymphocytic leukemia (CLL). The drug ibrutinib has caused quite a splash, but in the January 22, 2014, issue of the New England Journal of Medicine an important paper was published showing that another drug deserves our attention. That drug is idelalisib, a PI3 kinase delta isoform-specific inhibitor. The study by Furman and colleagues[1] was a randomized, placebo-controlled, double-blind trial of rituximab plus placebo vs rituximab plus the oral drug idelalisib in patients with relapsed CLL. This study included patients with impaired renal function, comorbidities, and myelosuppression from previous treatments, all factors that usually exclude patients from clinical trials.

The results were rather interesting. The median progression-free survival was 5.5 months for the placebo group vs not yet reached for the idelalisib group; the trial was stopped early because of overwhelming efficacy. There were improved rates of overall response: 81% in the idelalisib group vs 13% in the placebo group, and progression-free survival was significantly longer with idelalisib. But most notable was that the group receiving idelalisib saw an improvement in overall survival at the P = .02 level of significance. It is uncommon in studies of patients with CLL that anything really prolongs survival. We have had 1 or 2 upfront, initial treatment studies[2]; this is probably the only phase 3 study in the relapse setting.[3]

Having used this drug and having participated in the study, I have seen that the results can be rather dramatic. We have had patients whose bulky lymphadenopathy has virtually disappeared within a day or a few days of initiating therapy; however, it comes right back when therapy is discontinued for whatever reason.

In the study, patients tolerated treatment extremely well. We have seen some diarrhea and some fatigue, but in general, patients do quite well.

I am hopeful that studies like this will lead to the approval not only of ibrutinib, but also idelalisib, so that we will have multiple treatment options for patients with CLL. Our goal, at that time, will be to determine how we can select patients who will benefit from one or the other of these rather expensive drugs. It is a new world and our patients will certainly benefit from it.

This is Bruce Cheson, signing off for Medscape Hematology.


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