P648: REAL-WORLD TREATMENT AND OUTCOMES OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) RECEIVING FIRST-LINE (1L) THERAPY IN THE NOVEL AGENT ERA: AN INTERNATIONAL STUDY

Background: An expansion of treatment options in CLL makes it important to understand contemporary practice and treatment effectiveness. However, real-world data are still emerging regarding outcomes among different therapeutic options. Aims: The study goal was to describe treatment patterns and clinical outcomes of patients (pts) receiving 1L CLL treatment in real-world settings. Methods: Twenty three centers of the CLL Collaborative Study of Real-World Evidence (CORE), an international, retrospective, observational study, provided data for this analysis. Pts diagnosed with CLL/SLL were included if they were ≥18 years at diagnosis and initiated 1L therapy on/after 01/01/2014 and excluded if they participated in a clinical trial. Descriptive analyses were conducted to characterize pt demographics and clinical characteristics. Outcomes, including time to next treatment or death (TTNT-D) and progression-free survival (PFS), were estimated via the Kaplan-Meier (KM) method for the overall population and those with high-risk cytogenetics (del(17p)/TP53 and IGHV unmutated) or age ≥65. Results: Of 1,244 pts included in the study, between 2014-2022, 39% initiated CT/CIT in 1L (eg, bendamustine-rituximab [BR, 16%]; fludarabine-cyclophosphamide-rituximab [FCR, 9%]; obinutuzumab-chlorambucil [GClb, 5%]), 9% anti-CD20 monotherapy (eg, rituximab, 6%; obinutuzumab, 2%), 45% BTKi-based therapy (eg, ibrutinib, 42%; acalabrutinib, 3%), 7% venetoclax (Ven)-based therapy (eg, venetoclax-obinutuzumab [V+G, 5%]; venetoclax-rituximab [V+R, 1%]; venetoclax monotherapy, 1%), and 1% initiated other therapies over a median follow-up of 13-34 months. The median age was 63 years at diagnosis and 66 years at 1L initiation; 66% of pts were males, 35% had unmutated IGHV, and 15% had del(17p)/TP53, though 32-53% were not tested for IGHV and 10-18% for genetic mutations. Overall, the median TTNT-D (mTTNT-D) was 35, 18, 43 months for pts who received 1L therapy with CT/CIT, anti-CD20, and BTKi, respectively; mTTNT-D was not reached for Ven-based therapy over a median follow-up of 13 months. KM estimates of TTNT-D at month 24 were 64%, 42%, 69%, and 88% for CT/CIT, anti-CD20, BTKi, and Ven-based therapy, respectively (Table1). Trends were similar in subgroups: del(17p)/TP53, IGHV unmutated, or age ≥65. The median PFS (mPFS) was 39, 23, 51 months for pts who received CT/CIT, anti-CD20, and BTKi, respectively; mPFS was not reached for Ven-based therapy. KM estimates of PFS at month 24 were 67%, 48%, 80%, and 88% for CT/CIT, anti-CD20, BTKi- and Ven-based therapy, respectively (Table1). Similar trends were seen in subgroups: del(17p)/TP53, IGHV unmutated, or age ≥65. Patients categorized into the ‘other’ treatment group were not assessed due to low sample size (n=11; 1%).Summary/Conclusion: Our study presents contemporary practice and outcomes in CLL. We observed that almost 50% of pts were treated in the front-line setting with anti-CD20 monotherapy or CT/CIT despite availability of targeted agents. The continued use of anti-CD20 monotherapy and CT/CIT is surprising in the era of novel agents. Pts initiating 1L therapy with anti-CD20 or CT/CIT experienced worse clinical outcomes, providing further evidence of the effectiveness afforded by novel agents in 1L. Although mTTNT-D and mPFS were not reached for Ven-based therapy perhaps due to shorter follow-up, KM estimates tended to be higher through month 24, especially for high-risk and older pts. As the treatment paradigm continues to evolve, future exploration with larger cohorts and longer follow-up time should be undertaken. Keywords: Progression, Chemotherapy, Targeted therapy, Clinical outcome

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