TY - JOUR
T1 - The Connect CLL Registry
T2 - final analysis of 1494 patients with chronic lymphocytic leukemia across 199 US sites
AU - Mato, Anthony
AU - Nabhan, Chadi
AU - Lamanna, Nicole
AU - Kay, Neil E.
AU - Grinblatt, David L.
AU - Flowers, Christopher R.
AU - Farber, Charles M.
AU - Davids, Matthew S.
AU - Swern, Arlene S.
AU - Sullivan, Kristen
AU - Dawn Flick, E.
AU - Gressett Ussery, Sarah M.
AU - Gharibo, Mecide
AU - Kiselev, Pavel
AU - Sharman, Jeff P.
N1 - Funding Information:
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.
Funding Information:
Conflict-of-interest disclosure: 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,
Publisher Copyright:
© 2020 by The American Society of Hematology
PY - 2020/4/14
Y1 - 2020/4/14
N2 - 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.
AB - 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.
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U2 - 10.1182/bloodadvances.2019001145
DO - 10.1182/bloodadvances.2019001145
M3 - Article
C2 - 32271900
AN - SCOPUS:85083700651
SN - 2473-9529
VL - 4
SP - 1407
EP - 1418
JO - Blood Advances
JF - Blood Advances
IS - 7
ER -