A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia

• Published in: Blood 2015-12, Vol.126 (25), p.2686-2694
• Main Authors: O'Brien, Susan M., Lamanna, Nicole, Kipps, Thomas J., Flinn, Ian, Zelenetz, Andrew D., Burger, Jan A., Keating, Michael, Mitra, Siddhartha, Holes, Leanne, Yu, Albert S., Johnson, David M., Miller, Langdon L., Kim, Yeonhee, Dansey, Roger D., Dubowy, Ronald L., Coutre, Steven E.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Clinical Trials and Observations; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Male; Purines - administration & dosage; Purines - adverse effects; Quinazolinones - administration & dosage; Quinazolinones - adverse effects; Rituximab - administration & dosage; Rituximab - adverse effects; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2015-03-630947

Idelalisib is a first-in-class oral inhibitor of PI3Kδ that has shown substantial activity in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as initial therapy, 64 treatment-naïve older patients with CLL or small lymphocytic leukemia (median age, 71 years; range, 65-90) were treated with rituximab 375 mg/m2 weekly ×8 and idelalisib 150 mg twice daily continuously for 48 weeks. Patients completing 48 weeks without progression could continue to receive idelalisib on an extension study. The median time on treatment was 22.4 months (range, 0.8-45.8+). The overall response rate (ORR) was 97%, including 19% complete responses. The ORR was 100% in patients with del(17p)/TP53 mutations and 97% in those with unmutated IGHV. Progression-free survival was 83% at 36 months. The most frequent (>30%) adverse events (any grade) were diarrhea (including colitis) (64%), rash (58%), pyrexia (42%), nausea (38%), chills (36%), cough (33%), and fatigue (31%). Elevated alanine transaminase/aspartate transaminase was seen in 67% of patients (23% grade ≥3). The combination of idelalisib and rituximab was highly active, resulting in durable disease control in treatment-naïve older patients with CLL. These results support the further development of idelalisib as initial treatment of CLL. This study is registered at ClinicalTrials.gov as #NCT01203930. •In 64 older patients with untreated CLL or small lymphocytic leukemia, treatment with idelalisib plus rituximab was generally well tolerated.•The combination produced a very high response rate (97%), including 19% complete remission.