Time to second treatment can be used to predict overall survival in chronic lymphocytic leukemia: identifying risk factors to help guide treatment selection

Abstract

Targeted therapies have largely replaced chemoimmunotherapy (CIT) in first-line treatment of chronic lymphocytic leukemia (CLL). We aimed to develop a prognostic model to determine who would benefit from first-line CIT vs target therapy. In follicular lymphoma, time from diagnosis to second treatment (TT2T) correlates better with overall survival (OS) than time from diagnosis to first treatment (TT1T). We hypothesized that TT2T is a potential surrogate for OS in CLL. In a model-building cohort (n = 298), we evaluated potential predictors for TT2T and derived a risk score, which we validated in an external cohort (n = 1141). Our data demonstrated that TT2T and OS were more strongly correlated than TT1T and OS. Our risk score model consisted of three predictors (unmutated IGHV, β₂-microglobulin >297 nmol/L, and Rai stage I–IV), and was prognostic for TT2T and OS. TT2T is a promising surrogate for OS in CLL, but further validation is needed to establish this association.

Keywords:

• Chronic lymphocytic leukemia
• non-Hodgkin lymphoma
• survival
• chemoimmunotherapy
• targeted therapy
• prognostic model

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Author contributions

KSB designed the study, collected the data, performed the research, analyzed and interpreted the data, wrote the first draft of the manuscript, and was responsible for manuscript preparation and submission. ADZ designed the study, performed the research, analyzed and interpreted the data, and wrote the manuscript. NEK, SAP, KGR performed the research, analyzed and interpreted the data, and contributed to manuscript preparation. JDS, LER, and AM contributed to manuscript preparation. TGC, JFL, WD, and SLS collected the data.

Disclosure statement

NEK reports research support from Acerta Pharma, Bristol Myers Squibb, Pharmacyclics, Tolero Pharmaceuticals, MEI Pharma and Sunesis, data safety monitoring committee participation from Agios Pharm, AstraZeneca, Cytomyx Therapeutics, and Rigel, advisory board participation from Cytomx Therapy, Pharmacyclics, Juno Therapeutics, Astra Zeneca and Oncotracker. SAP reports research support from Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, Bristol Myers Squibb, AbbVie, and Ascentage Pharma, advisory board compensation from Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie. WD reports research funding from Merck, Abbvie, Octapharma, and DTRM, and advisory board participation from Octapharma, Beigene, MEI Pharma, and Alexion (she was not personally compensated for her participation). JDS reports consultancies from Adaptive Biotechnologies, research support from Roche/Genentech, TG Therapeutics, Beigene, Adaptive Biotechnologies, GlaxoSmithKline, and BostonGene, advisory board compensation from Seattle Genetics, Roche/Genentech, BMS, TG Therapeutics, Beigene, AstraZeneca, and Abbvie. LER reports consultancies from AstraZeneca, research support from American Society of Hematology, Pfizer, and Aptose Biosciences, speaker fees from Pfizer, Vaniam Group, and Abbvie, advisory board participation from Abbvie, Janssen/Pharmacyclics, Loxo Oncology, and TG Therapeutics, and stock ownership from Abbvie and Abbott Laboratories. AM has served as a consultant for Celgene, Acerta, and Janssen, has served as a consultant for and received research funding from AbbVie, Loxo, Genentech, Pharmacyclics, AstraZeneca, Sunesis, and Johnson & Johnson, has received research funding from DTRM Biopharma and Gilead, and has served as a consultant for, received research funding from, is a DSMB member, and other for TG Therapeutics. ADZ reports consultancies from Genentech/Roche, Gilead, Celgene, Janssen, Amgen, Novartis, Adaptive Biotech, MorphoSys, Abbvie, AstraZeneca, research support from MEI Pharma, Roche, Gilead, and Beigene, data safety monitoring committee chairmanship from Beigene, data safety monitoring board participation from Liso-cel, data safety monitoring committee membership from Juno, Celgene & Bristol Myers, scientific advisory board chairmanship from Lymphoma Research Foundation, and non-Hodgkin Lymphoma Panel chairmanship from National Comprehensive Cancer Network. KSB, KGR, TGC, JFL, and SLS declare no competing interests.

Additional information

Funding

This study was funded by the Lymphoma Research Foundation, the Lymphoma Research Fund (Andrew D. Zelenetz), the Henry J. Predolin Foundation, and the National Institutes of Health NIH P30 CA008748, RO1 AG58266 and RO1 CA 193541.