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.

• Authors: Jacob D Soumerai, Ai Ni, Guan Xing, Julie Huang, Richard R Furman, Jeffrey Jones, Jeffrey P Sharman, Michael Hallek, Adeboye H Adewoye, Ronald Dubowy, Lyndah Dreiling, Andrew D Zelenetz
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 60 Issue 6 Pg. 1438-1446 (06 2019) ISSN: 1029-2403 [Electronic] United States
• PMID: 30407886 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin Heavy Chains
• Immunoglobulin Variable Region
• Purines
• Quinazolinones
• idelalisib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Clinical Trials, Phase III as Topic
• Drug Resistance, Neoplasm (genetics)
• Female
• Follow-Up Studies
• Humans
• Immunoglobulin Heavy Chains (genetics)
• Immunoglobulin Variable Region (genetics)
• Kaplan-Meier Estimate
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, genetics, mortality, pathology)
• Male
• Middle Aged
• Models, Biological
• Multicenter Studies as Topic
• Neoplasm Recurrence, Local (drug therapy, genetics, mortality, pathology)
• Prognosis
• Purines (pharmacology, therapeutic use)
• Quinazolinones (pharmacology, therapeutic use)
• Risk Assessment (methods)
• Treatment Outcome