Idelalisib: Could This ‘B’ the Ideal Treatment For Chronic Lymphocytic Leukemia (CLL)?

 

The B-cell–receptor signaling pathway plays a key role in the pathogenesis of Chronic Lymphocytic Leukemia (CLL) and signaling is mediated in part by the activation of the delta isoform of phosphatidylinositol 3-kinase (PI3Kdelta), which is highly expressed in lymphoid cells. Idelalisib is a potent, oral, selective small-molecule inhibitor of PI3Kdelta.

In a recent study of elderly CLL patients (mostly over 65yrs) with advanced-stage disease, the standard CLL treatment of rituximab was compared with a combination of idelalisib plus rituximab. Patients in this study were heavily pre-treated and had received a median of three previous agents, including regimens containing rituximab, cyclophosphamide, fludarabine, and bendamustine.

The results of this study were so significant that the study was halted in order to gain fast track approval of this protocol for CLL patients.

  • The overall response rate was 81% (95% CI, 71 to 88) in the Idelalisib group, as compared with 13% (95% CI, 6 to 21) in the rituximab group (odds ratio, 29.92; P<0.001).
  • The median duration of progression-free survival (PFS) among patients in the idelalisib group was not reached during the study, whereas the PFS was only 5.5 months in the rituximab group.
  • The rate of overall survival (OS) in the idelalisib group was superior to that in the rituximab group (92% vs. 80% at 12 months), with an adjusted hazard ratio for death of 0.28 (95% CI, 0.09 to 0.86; P=0.02). The median duration of overall survival in the two groups had not yet been reached at the time of analysis. See Figure 1 below.

I like this approach because it targets an independent signalling pathway from rituximab, which targets CD20. But more important, it provides new life enhancing treatment options for patients with B-cell cancers that have failed on standard protocols.

Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia.

 

CTOAM Idelalisib and CLL


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