Unmet need in adults and adolescents and young adults (AYAs) with B-cell acute lymphoblastic leukemia (B-ALL) in the US following a second relapse.

e18510 Background: While new treatment modalities, such as the bispecific T-cell engager blinatumomab (blin) and chimeric antigen receptor modified T-cell (CAR-T) therapy, have improved outcomes in patients with B-ALL, a considerable proportion of patients are not cured with frontline therapy and require treatment for relapsed/refractory B-ALL. The aim of this study was to understand the unmet need in patients with B-ALL who have relapsed after 2 lines of therapy for B-ALL using real-world data. Methods: This retrospective, observational cohort study used patient data from US nationwide longitudinal Flatiron Health Research Database, from January 1, 2014 to March 31, 2024. Patients aged ≥ 12 years with an initial diagnosis of B-ALL who had received 2 prior lines of therapy specific for B-ALL were included. The index date was the date of second relapse for B-ALL. Here we report the proportion of patients requiring third-line (3L) treatment and the breakdown of 3L treatments overall and by age. Results: 388 patients who initiated first-line (1L) treatment were identified, and of these, 195 (50%) initiated 3L treatment. Of the patients initiating 3L treatment, 33% were AYAs aged 12–40 years, 43% were aged 41–64 years, 19% were aged 65–74 years, and 5% were aged > 75 years. The most common 3L treatments were multi-agent chemotherapy (155 patients) followed by blin-containing regimens (71 patients) and inotuzumab-containing regimens (56 patients; Table). One-quarter (27%) of patients receiving blin in 3L were receiving retreatment following blin in 1L or second-line treatment. Only 4% of patients receiving 3L treatment received commercial CAR-T. Conclusions: Half of adults and AYAs with B-ALL who received 1L treatment went on to require 3L treatment. The majority (76%) of patients requiring 3L treatment were AYAs and adults aged 41–64 years. The most common 3L treatment was multi-agent chemotherapy, followed by blin. This highlights a major unmet need for effective therapies in the 3L setting. Distribution of 3L treatments by age. Regimen, n (%) AYA aged 12–40 yearsn = 65 Aged 41–64 yearsn = 83 Aged 65–74 yearsn = 37 Aged > 75 yearsn = 10 TotalN = 195 Multi-drug chemotherapy 53 (82) 63 (76) 31 (84) 8 (80) 155 (79) Blin-containing 26 (40) 24 (29) 18 (49) 3 (30) 71 (36) Blin-containing (retreatment) 7 (11) 5 (6) 6 (16) 1 (10) 19 (10) Inotuzumab-containing 17 (26) 25 (30) 11 (30) 3 (30) 56 (29) Tyrosine kinase inhibitor-containing 5 (8) 28 (34) 9 (24) 2 (20) 44 (23) Hematopoietic stem cell transplant 14 (22) 21 (25) 6 (16) 1 (10) 42 (22) Palliative 3 (5) 10 (12) 0 0 13 (7) Clinical study drug-containing 2 (3) 8 (10) 2 (5) 0 12 (6) CAR-T 4 (6) 3 (4) 0 0 7 (4) Categories are not mutually exclusive. 193 patients who initiated 1L treatment did not receive 3L treatment. AYA, adolescent and young adult; blin, blinatumomab; CAR-T, chimeric antigen receptor modified T-cell; 1L, first-line; 3L, third-line.