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Author Notes:

Correspondence: Anthony Mato, CLL Program, Leukemia Service, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; e-mail: matoa@mskcc.org

Author contributions: A.M., C.N., N.L., N.E.K., D.L.G., C.R.F., C.M.F., M.S.D., and J.P.S. recruited patients to the Registry; P.K. and A.S.S. completed the statistical analyses; and all authors interpreted the data, directed the development, review, and approval of this manuscript, and are fully responsible for all content and editorial decisions.

The authors thank all the patients and their families who participated in the Connect CLL Registry. The Connect CLL Scientific Steering Committee acknowledges the contributions of all past and current members of the committee for their guidance in the design of the Registry, and participation in analysis of the data, including:

Matthew S. Davids, Charles M. Farber, Ian Flinn, Christopher R. Flowers, David L. Grinblatt, Neil E. Kay, Michael Keating, Thomas J. Kipps, Mark F. Kozloff, Nicole Lamanna, Susan Lerner, Anthony Mato, Chadi Nabhan, Chris L. Pashos, Jeff P. Sharman, and Mark Weiss.

The Connect CLL Registry is sponsored and funded by Bristol-Myers Squibb. The sponsor supported the authors in collecting and analyzing the data reported in this Registry. The authors received medical writing support in the preparation of this manuscript from Victoria Edwards and Nicky Dekker of Excerpta Medica BV, supported by Bristol-Myers Squibb.

Disclosures: A.M. has been a consultant for AbbVie, Adaptive, AstraZeneca, Celgene Corporation (including data safety monitoring board), Genentech, Johnson & Johnson, LOXO, Regeneron, Pharmacyclics, Sunesis, and TG Therapeutics (including data safety monitoring board); and has received research funding from AbbVie, Acerta, Adaptive, DTRM, Genentech, Johnson & Johnson, Regeneron, LOXO, Pharmacyclics, Portola, and TG Therapeutics.

C.N. is employed by Aptitude Health.

N.L. has received research funding from AbbVie, AstraZeneca, BeiGene, Genentech, Gilead, Infinity Pharma, Juno, Ming, ProNAi, and TG Therapeutics; been a consultant for AbbVie, AstraZeneca, BeiGene, Genentech, Gilead, Juno, ProNAi, and Pharmacyclics; and served on an advisory committee for Celgene Corporation.

N.E.K. has received research funding from Gilead, Celgene Corporation, Hospira, Genentech, and Pharmacyclics and been on advisory committees for Gilead and Celgene Corporation.

D.L.G. has been a consultant and member of a speaker’s bureau for Celgene Corporation. C.R.F. has received research funding from Gilead, Spectrum, Millennium, Janssen, Infinity Pharma, AbbVie, Acerta, Pharmacyclics, and TG Therapeutics; served as a consultant for Celgene Corporation, OptumRx, Gilead, Seattle Genetics, Millennium, and Genentech/Roche; and received honoraria from Celgene Corporation.

C.M.F. has received research funding from Genentech and Gilead; been a consultant and part of a speaker’s bureau for Celgene Corporation, Gilead, Janssen, Pharmacyclics, Seattle Genetics, and Genentech; served on an advisory committee for Celgene Corporation; and received honoraria from Janssen.

M.S.D. has served as a consultant for AbbVie, Acerta Pharma, Adaptive Biotechnologies, AstraZeneca, Genentech, Gilead, Janssen, MEI Pharma, Pharmacyclics, Research to Practice, Syros Pharmaceuticals, TG Therapeutics, and Verastem and received research funding from Acerta Pharma, Ascentage Pharma, Bristol-Myers Squibb, Genentech, MEI Pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, and Verastem.

A.S.S., K.S., E.D.F., M.G., and P.K. are employees of Bristol-Myers Squibb and have equity. S.M.G.U. is a former employee of Celgene Corporation (now Bristol-Myers Squibb).

J.P.S. has received honoraria from Genentech, Gilead, and TG Therapeutics; been a consultant for Celgene Corporation, Genentech, Gilead, and Pharmacyclics; been a member of a speaker’s bureau for Gilead; received research funding from Celgene Corporation, Genentech, Gilead, Pharmacyclics, TG Therapeutics, Seattle Genetics, and Acerta; and received travel expenses from Celgene Corporation and Gilead.

Subjects:

Research Funding:

None declared

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology
  • Open label
  • Rituximab
  • Chemoimmunitherapy
  • Cyclophosphamide
  • Bendamustine
  • Fludarabine
  • Guidelines
  • Diagnosis
  • Survival
  • Phase-3

The Connect CLL Registry: final analysis of 1494 patients with chronic lymphocytic leukemia across 199 US sites

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Journal Title:

Blood Advances

Volume:

Volume 4, Number 7

Publisher:

, Pages 1407-1418

Type of Work:

Article | Final Publisher PDF

Abstract:

Optimal treatment of chronic lymphocytic leukemia (CLL) remains unclear. The Connect CLL Registry, a United States-based multicenter prospective observational cohort study, enrolled 1494 patients between 2010 and 2014 from predominantly community-based settings. Patients were grouped by line of therapy (LOT) at enrollment. With a median follow-up of 46.6 months (range, 0-63.0 months), median overall survival (OS) was not reached in LOT1, 63.0 months (95% confidence interval [CI], 46.0-63.0 months) in LOT2, and 38.0 months (95% CI, 33.0-47.0 months) in LOT$3. Bendamustine and rituximab (BR; 33.5%); fludarabine, cyclophosphamide, and rituximab (FCR; 21.4%); and rituximab monotherapy (18.5%) were the most common regimens across LOTs. Median event-free survival (EFS) was similar in patients treated with BR (59.0 months) and FCR (55.0 months) in LOT1; median OS was not reached. In multivariable analysis, BR or FCR vs other treatments in LOT1 was associated with improved EFS (hazard ratio [HR], 0.60; P , .0001) and OS (0.67; P 5 .0162). Using the Kaplan-Meier product limit, ibrutinib vs other treatments improved OS in LOT2 (HR, 0.279; P 5 .009), LOT3 (0.441; P 5 .011), and LOT$4 (0.578; P 5 .043). Prognostic modeling of death at 2 years postenrollment identified 3 risk groups: low (mortality rate, 6.2%), medium (14.5%), and high (27.4%). The most frequent adverse events across LOTs were pneumonia (11.6%) and febrile neutropenia (6.2%). These data suggest that advantages of LOT1 FCR over BR seen in clinical trials may not translate to community practice, whereas receiving novel LOT2 agents improved outcomes. This trial was registered at www.clinicaltrials.gov as NCT01081015.

Copyright information:

© 2020 by The American Society of Hematology.

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