Results of the Phase 3 DUO study evaluating duvelisib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) have been reported and appear very promising. Although the treatment of CLL/SLL has advanced in recent years, there remains a substantial unmet need with many patients progressing or relapsing following the available therapies and new treatment options are needed.
Duvelisib is an investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3
The DUO clinical study evaluated 319 patients with advanced CLL/SLL treated with duvelisib or Azerra (ofatumumab) and directly compared. Overall oral duvelisib monotherapy was well tolerated, and showed superiority compared to Azerra attaining an average survival without cancer progression of 13.3 months, compared to 9.9 months. The benefit was observed in CLL/SLL patients with and without the 17p deletion a known poor prognostic subgroup.
1 Winkler et al. PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol 2013; 20:1-11.
2 Reif et al. Cutting Edge: Differential roles for phosphoinositide 3 kinases, p110-gamma and p110-delta, in lymphocyte chemotaxis and homing. J Immunol 2004:173:2236-2240.
3 Schmid et al. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3K, a single convergent point promoting tumor inflammation and progression. Cancer Cell 2011;19:715-727.
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