Evaluation of the CLL-IPI in relapsed and refractory chronic lymphocytic leukemia in idelalisib phase-3 trials

Abstract

The CLL-IPI is a risk-weighted prognostic model for previously untreated patients with chronic lymphocytic leukemia (CLL), but has not been evaluated in patients with relapsed CLL or on novel therapies. We evaluated the CLL-IPI in 897 patients with relapsed/refractory CLL in 3 randomized trials testing idelalisib (PI3Kδ inhibitor). The CLL-IPI identified patients as low (2.2%), intermediate (12.8%), high (48.7%), and very high (36.2%) risk and was prognostic for survival (log-rank p < .0001; C-statistic 0.706). Of CLL-IPI factors, age >65, β2-microglobulin >3.5mg/L, unmutated immunoglobulin heavy chain variable region gene, and deletion 17p/TP53 mutation were independently prognostic, but Rai I-IV or Binet B/C was not. The CLL-IPI is prognostic for survival in relapsed CLL and with idelalisib therapy. However, low/intermediate risk is uncommon, and regression parameters of individual factors in this risk-weighted model appear different in relapsed CLL. Reassessment of the weighting of the individual variables might optimize the model in this setting.

Keywords:

• Chronic lymphocytic leukemia
• CLL-IPI
• idelalisib
• lymphoma
• leukemia
• prognostication

Acknowledgments

The authors would like to thank all the patients who participated as well as all the clinicians and research staff contributing to the conduct of the clinical trials.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://doi.org/10.1080/10428194.2018.1540782.

Additional information

Funding

Jacob D. Soumerai received consultancy fees from Verastem; Richard R. Furman received consultancy fees from Janssen, Gilead, Pharmacyclics, Abbvie, Verastem, TG Therapeutics, Genentech, Incyte, Loxo Oncology, and Sunesis. Jeffrey Jones received personal fees as an advisory board member for Gilead; Jeffrey P. Sharman received consultancy fees, research funding, and honoraria from Gilead and TG therapeutics; Michael Hallek received consultancy fees, research funding, and honoraria from Abbvie, Janssen, and Gilead, and speakers bureau fees from Gilead; Andrew D. Zelenetz received consultancy fees from Genentech, Roche, Gilead, Celgene, Janssen, Amgen, Novartis, and Adaptive Biotechnologies, research funding from MEI Pharma, Roche, and Gilead, and served as the DMC chair for Beigene; Guan Xing, Julie Huang, Ming Lin, Adeboye H. Adewoye, Ronald Dubowy, and Lyndah Dreiling are employed by Gilead.

This work was supported by the Lymphoma Research Foundation under Lymphoma Clinical Research Mentoring Program Grant number (498061) and Lymphoma Clinical Research Mentoring Program (498061); the NIH/NCI under Cancer Center Support Grant (P30 CA008748); and the clinical trials were supported by Gilead Sciences, Inc.