Update on a phase I study of the selective PI3Kδ inhibitor idelalisib (GS-1101) in combination with rituximab and/or bendamustine in patients with relapsed or refractory CLL.
2013; Lippincott Williams & Wilkins; Volume: 31; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2013.31.15_suppl.7017
ISSN1527-7755
AutoresJacqueline C. Barrientos, Richard R. Furman, John P. Leonard, Ian W. Flinn, Kanti Roop, Sven de Vos, Marshall T. Schreeder, Nina D. Wagner‐Johnston, Jeff P. Sharman, Thomas E. Boyd, Nathan Fowler, Leanne Holes, David M. Johnson, Daniel Li, Roger Dansey, Thomas M. Jahn, Steven Coutré,
Tópico(s)Monoclonal and Polyclonal Antibodies Research
Resumo7017 Background: PI3K-delta signaling is critical for proliferation, survival, homing and tissue retention of malignant B cells. Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ that has shown considerable monotherapy activity in pts with heavily pretreated CLL. Methods: This phase I study evaluated idelalisib continuously given at 150 mg BID in combination with rituximab (R, 375 mg/m 2 every wk x 8), bendamustine (B, 70 or 90 mg/m 2 x 2, every 4 wks x 6) or BR (every 4 wks x 6) for relapsed/refractory CLL. Pts still on treatment after 48 weeks were eligible to continue idelalisib on an extension study. Clinical response was evaluated according to published criteria (Hallek 2008; Cheson 2012). Results: 52 pts (23F/29M) with a median (range) age of 64 (41-87) years were enrolled. Adverse disease characteristics included bulky lymphadenopathy (62%), refractory disease (50%), multiple prior therapies (median 3, range: 1-14) with 96% receiving prior R and 44% receiving prior B. As of 14 Jan 2013, the median (range) treatment duration was 18 (1-33) months. 31/52 (60%) pts enrolled into the extension study; of those, 24/52 (46%) pts are continuing idelalisib treatment on the extension study. The ORR was 81%, with 1 CR, and a median (range) time to response of 1.9 (1.5-8.3) months. The 2-year PFS and OS were 62% and 85%, respectively. At 2 years follow up, 71% of responses were still enduring. There was no difference in outcomes for pts with <3 prior treatments (n=21) vs ≥3 prior treatments (n=31). The most common TEAEs (any Grade/≥Gr 3, independent of causality) included pyrexia (44%/6%), diarrhea (40%/14%), cough (31%/2%), fatigue (29%/2%), nausea (29%/0%). Pneumonia (any Gr/≥Gr 3) occurred in 15%/12% and rash was seen in 15%/0%. 10% of patients experienced ≥Gr 3 ALT/AST elevation based on laboratory values. Conclusions: A lack of overlapping toxicities allowed idelalisib to be co-administered with R, B, or BR, and all 3 combination regimens were highly active, resulting in durable tumor control in pts with heavily pretreated relapsed/refractory CLL. Phase III trials evaluating the efficacy of idelalisib in combination with R or BR are ongoing. Clinical trial information: NCT01088048.
Referência(s)