A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia Journal Article
| Authors: | O'Brien, S. M.; Lamanna, N.; Kipps, T. J.; Flinn, I.; Zelenetz, A. D.; Burger, J. A.; Keating, M.; Mitra, S.; Holes, L.; Yu, A. S.; Johnson, D. M.; Miller, L. L.; Kim, Y.; Dansey, R. D.; Dubowy, R. L.; Coutre, S. E. |
| Article Title: | A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia |
| Abstract: | Idelalisib is a first-in-class oral inhibitor of PI3Kd 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 375mg/m2 weekly ×8andidelalisib 150mgtwice 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. © 2015 by The American Society of Hematology. |
| Keywords: | aged; gene mutation; major clinical study; constipation; fatigue; diarrhea; drug dose reduction; drug efficacy; drug safety; side effect; cancer patient; rituximab; progression free survival; drug eruption; multiple cycle treatment; pharmacodynamics; phase 2 clinical trial; nausea; vomiting; dehydration; steroid; protein p53; alanine aminotransferase blood level; arthralgia; aspartate aminotransferase blood level; backache; chill; coughing; dyspnea; febrile neutropenia; fever; pneumonia; pruritus; hypoxia; alanine aminotransferase; aspartate aminotransferase; drug induced headache; insomnia; heart infarction; urinary tract infection; glucocorticoid; colitis; chronic lymphatic leukemia; geriatric patient; cytomegalovirus infection; analgesic agent; night sweat; antihistaminic agent; opportunistic infection; respiratory failure; cellulitis; valaciclovir; idelalisib; human; male; female; priority journal; article |
| Journal Title: | Blood |
| Volume: | 126 |
| Issue: | 25 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2015-12-17 |
| Start Page: | 2686 |
| End Page: | 2694 |
| Language: | English |
| DOI: | 10.1182/blood-2015-03-630947 |
| PROVIDER: | scopus |
| PUBMED: | 26472751 |
| PMCID: | PMC4732760 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 February 2016 -- Source: Scopus |
