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. 2025 Feb 26;17(5):799.
doi: 10.3390/cancers17050799.

Real-World Effectiveness of Frontline Treatments Among Patients with Chronic Lymphocytic Leukemia: Results from ConcertAI

Lindsey E Roeker  1 , John M Burke  2 , Joanna M Rhodes  3 , Nnadozie Emechebe  4 , Dureshahwar Jawaid  4 , Beenish S Manzoor  4 , Christopher E Jensen  5 , Lindsay Ryland  4 , Yangyang Liu  4 , Steve E Marx  4 , Wendy Sinai  4 , Jordan Roser  4 , Mazyar Shadman  6
Affiliations

Real-World Effectiveness of Frontline Treatments Among Patients with Chronic Lymphocytic Leukemia: Results from ConcertAI

Lindsey E Roeker et al. Cancers (Basel). .

Abstract

Background: The long-term follow-up of clinical trials of novel first-line (1L) therapies for chronic lymphocytic leukemia (CLL) demonstrates 6-10-year progression-free survival. We describe the effectiveness of 1L CLL treatments in real-world settings, with an emphasis on the important real-world outcome of time to next treatment or death (TTNT-D). Methods: This retrospective, observational study utilized de-identified electronic health records from the ConcertAI RWD360™ database with linked administrative open claims. Adults with CLL who initiated an approved 1L CLL therapy (June 2019-March 2023) were included. Duration of therapy (DoT), TTNT-D, and overall survival were assessed. Results: At 1L, 39.8% of 1843 patients received first-generation covalent Bruton tyrosine kinase inhibitors (cBTKis), 23.0% second-generation cBTKis, 12.4% venetoclax-obinutuzumab (VenO), 7.4% chemotherapy/chemoimmunotherapy (CT/CIT), and 17.4% anti-CD20 monotherapy. Median (range) follow-up in months was 24.9 (13.1-36.6) for first-generation cBTKis, 13.4 (7.3-21.7) for second-generation cBTKis, 16.0 (8.4-27.8) for VenO, 21.8 (11.2-32.7) for CT/CIT, and 19.7 (10.0-33.4) for anti-CD20 monotherapy. Median (range) DoT was 11.5 (4.2-25.0) and 8.6 (3.0-16.1), 9.1 (5.9-12.2), 5.6 (3.2-5.8), and 1.6 (1.6-4.5) months for first- and second-generation cBTKis, VenO, CT/CIT, and anti-CD20 monotherapy, respectively. Regarding TTNT-D, at 2 years' follow-up, 69.1%, 82.5%, 86.3%, 79.1%, and 53.0% of patients treated with first- and second-generation cBTKis, VenO, CT/CIT, and anti-CD20 monotherapy, respectively, had not initiated subsequent treatment or experienced death. Conclusions: TTNT-D is an important real-world outcome in CLL. Our findings demonstrated the utility of time-limited VenO, with potentially more time off treatment, relative to continuous 1L cBTKi therapies.

Keywords: chronic lymphocytic leukemia; real-world outcomes; treatment effectiveness.

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Conflict of interest statement

L.E.R.: Consultant for AbbVie, Ascentage, AstraZeneca, BeiGene, Janssen, Loxo Oncology, Pharmacyclics, Pfizer, and TG Therapeutics; member of a data safety monitoring committee for Ascentage; served as a CME speaker for DAVA, Curio, Medscape, and PeerView; holds minority ownership interest in Abbott Laboratories; received travel support from LOXO oncology; and received research funding (paid to the institution) from Adaptive Biotechnologies, AstraZeneca, Genentech, AbbVie, Pfizer, Loxo Oncology, Aptose Biosciences, Dren Bio, and Qilu Puget Sound Biotherapeutics. J.M.B.: Consulting or advisory role: Genentech/Roche, AbbVie, AstraZeneca, Adaptive Biotechnologies, BeiGene, Novartis, Bristol Myers Squibb, Nurix, Genmab, Foresight Diagnostics, Regeneron, and Seagen; speakers’ bureau: Seagen and BeiGene; travel, accommodations, and expenses: Genentech/Roche. J.M.R.: Consultant: Verastem, AbbVie/Genentech, PCYC, and AstraZeneca. C.E.J.: Consultancy: AbbVie. M.S.: Consulting, advisory boards, steering committees, or data safety monitoring committees: AbbVie, Genentech, AstraZeneca, Genmab, Janssen, Beigene, Bristol Myers Squibb, Morphosys/Incyte, Kite Pharma, Eli Lilly, Mustang Bio, Fate Therapeutics, Nurix, and Merck; institutional research funding from Mustang Bio, Genentech, AbbVie, BeiGene, AstraZeneca, Genmab, Morphosys/Incyte, and Vincerx; stock options: Koi Biotherapeutics; employment: Bristol Myers Squibb (spouse). N.E., D.J., B.S.M., L.R., Y.L., W.S., and J.R.: Employees of AbbVie and may hold stock or stock options. S.E.M.: Retired from AbbVie.

Figures

Figure 1
Figure 1
Distribution of 1L regimens by treatment groups. Others included fludarabine, cyclophosphamide, rituximab, and other CT/CIT agents. 1L, first-line; aCD20, anti-CD20; BR, bendamustine plus rituximab; cBTKi, covalent Bruton tyrosine kinase inhibitor; CT/CIT, chemotherapy/chemoimmunotherapy; gen, generation; VenO, venetoclax plus obinutuzumab.
Figure 2
Figure 2
Real-world TTNT-D for CLL treatments in 1L. 1L, first-line; aCD20, anti-CD20; cBTKi, covalent Bruton tyrosine kinase inhibitor; CI, confidence interval; CLL, chronic lymphocytic leukemia; CT/CIT, chemotherapy/chemoimmunotherapy; gen, generation; NE, not estimable; KM, Kaplan–Meier; TTNT-D, time to next treatment or death; VenO, venetoclax plus obinutuzumab.
Figure 3
Figure 3
Real-world OS for CLL treatments in 1L. 1L, first-line; aCD20, anti-CD20; cBTKi, covalent Bruton tyrosine kinase inhibitor; CI, confidence interval; CLL, chronic lymphocytic leukemia; CT/CIT, chemotherapy/chemoimmunotherapy; gen, generation; KM, Kaplan–Meier; NE, not estimable; OS, overall survival; VenO, venetoclax plus obinutuzumab.
Figure 4
Figure 4
Real-world TTNT for CLL treatments in 1L: sensitivity analysis. 1L, first-line; aCD20, anti-CD20; cBTKi, covalent Bruton tyrosine kinase inhibitor; CI, confidence interval; CLL, chronic lymphocytic leukemia; CT/CIT, chemotherapy/chemoimmunotherapy; gen, generation; KM, Kaplan–Meier; NE, not estimable; TTNT-D, time to next treatment or death; VenO, venetoclax plus obinutuzumab.
Figure 5
Figure 5
Real-world OS for CLL treatments in 1L: sensitivity analysis. 1L, first-line; aCD20, anti-CD20; cBTKi, covalent Bruton tyrosine kinase inhibitor; CI, confidence interval; CLL, chronic lymphocytic leukemia; CT/CIT, chemotherapy/chemoimmunotherapy; gen, generation; KM, Kaplan–Meier; NE, not estimable; OS, overall survival; VenO, venetoclax plus obinutuzumab.
Figure 6
Figure 6
Subsequent treatments received at 2L stratified by 1L treatment groups. Other treatments included duvelisib (n = 1) and lenalidomide (n = 4). 1L, first-line; 2L, second-line; aCD20, anti-CD20; cBTKi, covalent Bruton tyrosine kinase inhibitor; CT/CIT, chemotherapy/chemoimmunotherapy; gen, generation; VenO, venetoclax plus obinutuzumab.
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