The CLL International Prognostic Index predicts outcomes in monoclonal B-cell lymphocytosis and Rai 0 CLL

Sameer A. Parikh, Kari G. Rabe, Neil E. Kay, Timothy G. Call, Wei Ding, Jose F. Leis, Saad S. Kenderian, Eli Muchtar, Yucai Wang, Amber B. Koehler, Susan M. Schwager, Connie E. Lesnick, Geffen Kleinstern, Daniel Van Dyke, Curtis A. Hanson, Esteban Braggio, Susan L. Slager, Tait D. Shanafelt

Research output: Contribution to journalArticlepeer-review

Abstract

The utility of the chronic lymphocytic leukemia-international prognostic index (CLL-IPI) in predicting outcomes of individuals with Rai 0 stage CLL and monoclonal B-cell lymphocytosis (MBL) is unclear. We identified 969 individuals (415 MBL and 554 Rai 0 CLL; median age, 64 years; 65% men) seen at Mayo Clinic between 1 January 2001 and 1 October 2018, and ascertained time to first therapy (TTFT) and overall survival (OS). After a median follow up of 7 years, the risk of disease progression needing therapy was 2.9%/y for MBL (median, not reached) and 5%/y for Rai 0 CLL (median, 10.4 years). Among patients with low, intermediate, and high/very high-risk CLL-IPI risk groups, the estimated 5-year risk of TTFT was 13.5%, 30%, and 58%, respectively, P < .0001 (c-statistic = 0.69); and the estimated 5-year OS was 96.3%, 91.5%, and 76%, respectively, P < .0001 (c-statistic = 0.65). In a multivariable analysis of absolute B-cell count with individual factors of the CLL-IPI, the absolute B-cell count was associated with shorter TTFT (hazard ratio [HR] for each 10 × 109/L increase: 1.31; P < .0001) and shorter OS (HR: 1.1; P = .02). The OS of the entire cohort was similar to that of the age- and sex-matched general population of Minnesota (P = .17), although Rai 0 CLL patients with high and very high-risk CLL-IPI score had significantly shorter OS (P = .01 and P = .0001, respectively). The results of this study demonstrate the ability of CLL-IPI to predict time from diagnosis to first treatment (an end point not affected by therapy) in a large cohort of patients whose only manifestation of disease is a circulating clonal lymphocyte population.

Original languageEnglish
Pages (from-to)149-159
Number of pages11
JournalBlood
Volume138
Issue number2
DOIs
StatePublished - 15 Jul 2021

Bibliographical note

Funding Information:
Conflict-of-interest disclosure: S.A.P. reports that research funding has been provided to the institution from Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, Bristol Myers Squibb, Merck, AbbVie, and Ascentage Pharma for clinical studies in which S.A.P. is a principal investigator; S.A.P. has also participated in Advisory Board meetings of Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie (but was not personally compensated for his participation). N.E.K. reports research funding from Acerta Pharma, Pharmacyclics, MEI Pharma, and Tolero; he is on a data safety monitoring committee for Agios Pharm, Celgene, Sunesis, CytomX Therapeutics, MorphoSys, Rigel Pharm, and Juno Therapeutics. N.E.K. is on an advisory board for Astra Zeneca, CytomX Therapeutics, Pharmacyclics, Dava Oncology, Acerta Pharma BV, and Juno Therapeutics. W.D. reports research funding from Determine and Merck, and advisory board participation for Merck and Octapharma. S.S.K. is an inventor on patents in the field of CAR immunotherapy that are licensed to Novartis (through an agreement between Mayo Clinic, University of Pennsylvania, and Novartis). S.S.K. is an inventor on patents in the field of CAR immunotherapy that are licensed to Humanigen (through Mayo Clinic). S.S.K. is an inventor on patents in the field of CAR immunotherapy that are licensed to Mettaforge (through Mayo Clinic). S.S.K. receives research funding from Kite, Gilead, Juno, Celgene, Novartis, Humanigen, MorphoSys, Tolero, Sunesis, and Lentigen. Y.W. reports research funding (to the institution) from Incyte, InnoCare, Novartis, and Genentech. E.B. is a consultant of DASA. E.B reports serving as a cunsultant for DASA. T.D.S. reports research support to institution from Pharmacyclics and Genentech. The remaining authors declare no competing financial interests.

Funding Information:
This work was supported by grants from the National Institutes of Health, National Cancer Institute (R01 CA235026 and R01 CA197120). The conduct of this research was supported, in part, by the Henry J. Predolin Foundation. S.A.P. and S.S.K. also acknowledge support from the Mayo Clinic K2R Career Development Program.

Publisher Copyright:
© 2021 American Society of Hematology

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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