Bloomquist, Erik W.

e19025 Background: Recent studies suggest that patients with CLL/SLL (herein, CLL) relapsed/refractory (R/R) to both cBTKi and BCL2i (double R/R [DR]) may have poorer outcomes than the broader group of double-exposed (DE) patients. This study evaluated real-world response (rwR) and time-to-event (TTE) outcomes of a CLL DE cohort and DR subcohort in the US. Methods: This retrospective study used the nationwide Flatiron Health electronic health record-derived deidentified database to include patients with CLL treated with sequential or combination cBTKi and BCL2i in any line of therapy (LOT) on or after January 1, 2011, and a subsequent LOT (ie, index LOT) on or before November 30, 2022 (DE cohort). A subset with DR CLL (DR subcohort) was analyzed separately. Descriptive statistics were generated for demographic and clinical characteristics. Outcomes included clinician-confirmed rwR rate (rwRR) and median TTE outcomes (real-world duration of response [rwDOR], progression-free survival [rwPFS], time to next treatment [rwTTNT], and overall survival [rwOS]; Kaplan Meier, follow-up to May 31, 2023). Results: The DE cohort included 264 patients, 107 of whom were in the DR subcohort. Patients were mostly male (64%), White (75%), aged ≥65 years at first index LOT (72%) after prior cBTKi and BCL2i treatment, and treated in the community setting (71%). Approximately one-third of patients received a subsequent treatment after each index LOT. Most patients were re-treated with a cBTKi and/or BCL2i in the first index LOT (69% DE; 54% DR), and the percentage treated with chemotherapy increased with each subsequent index LOT. Confirmed rwRR was similar between DE and DR for all index LOTs (Table). More relevant are the median TTE outcomes, which were shorter for DR than DE, especially for the first index LOT, and shorter in subsequent index LOTs for both groups. Conclusions: The high percentage of patients re-treated with cBTKi and BCL2i therapies and increasing use of chemotherapy regimens with each subsequent index LOT indicate a lack of standard of care and options. Our results suggest a high unmet need in the DE CLL population, particularly in patients DR to cBTKi and BCL2i therapy, who have worse outcomes. Efficacious and durable therapy options are needed to address this unmet need. Double Exposed Index LOT Double R/R Index LOT 1st 2nd 3rd 1st 2nd 3rd N 264 90 35 107 41 12 rwRR, % (95% CI) 39(33-45) 42(32-53) 40(24-58) 36(27-45) 34(21-51) 42(16-71) Median TTE outcomes, months (95% CI) rwDOR 20.3 (13.5-32.6) 6.0(5.5-NR) 3.1(2.7-NR) 11.5 (7.9-23.5) 6.0(3.6-NR) 2.9(2.7-NR) rwPFS 8.8(7.5-10.6) 5.1(4.0-7.3) 4.3(2.9-6.3) 5.0 (4.0-7.3) 3.6(2.6-5.7) 4.7(2.7-NR) rwTTNT 13.8 (10.3-18.3) 7.9(5.7-11.3) 5.7(4.2-14.6) 8.0 (6.2-11.5) 5.9(4.4-11.4) 5.0(4.2-NR) rwOS 25.2 (22.1-37.1) 15.2(11.4-22.6) 6.6(5.7-NR) 14.7 (12.3-22.6) 11.4(5.9-NR) 6.6(5.0-NR)

Abstract On July 24, 2020, a workshop sponsored by the National Brain Tumor Society was held on innovating brain tumor clinical trials based on lessons learned from the COVID-19 experience. Various stakeholders from the brain tumor community participated including the US Food and Drug Administration (FDA), academic and community clinicians, researchers, industry, clinical research organizations, patients and patient advocates, and representatives from the Society for Neuro-Oncology and the National Cancer Institute. This report summarizes the workshop and proposes ways to incorporate lessons learned from COVID-19 to brain tumor clinical trials including the increased use of telemedicine and decentralized trial models as opportunities for practical innovation with potential long-term impact on clinical trial design and implementation.