Background: CRLF2 rearranged B-ALL, a subtype of Ph-like ALL, constitutes a high-risk subset of B-ALL with poor outcomes with chemotherapy. Targeted therapies such as blinatumomab (blina) or inotuzumab (ino) may improve treatment outcomes for these patients (pts). Methods: We retrospectively analyzed pts with newly diagnosed B-ALL (diagnosed between 01/2001 and 12/2021) at our center who had documented CRLF2 overexpression. Initial therapy, including use of ino and blina in CR1 were noted. Outcomes measures included CR/CRi, MRD response, RFS and OS. Results: A total of 76 pts with a median age of 38 years (yrs) (range, 18-80) were identified, of which 70% were males and 81% were of Hispanic ethnicity. All pts had overexpression of CRLF2 documented by flow cytometry or gene expression profile. A subset of pts (n=37) had a concomitant CRLF2 FISH performed with all confirming CRLF2 rearrangement. Baseline disease parameters, treatment and outcomes are detailed in Table. Sixty-five pts (85%) received Hyper-CVAD based induction therapy (HCVAD, n=51; mini-HCVD, n=14) and 11 (15%) received augmented BFM. Among the HCVAD/mini-HCVD treated pts, 37% received blina in CR1 during consolidation at a median of 3.6 months after starting induction therapy, 34% received ino in CR1 (most commonly starting in cycle 1 as part of mini-HCVD + ino regimen) and 22% received both ino and blina in CR1. We focus on the outcomes of 65 pts treated with HCVAD/mini-HCVD. The median follow-up was 18 months (mos). CR/CRi rate after C1 among HCVAD/mini-HCVD treated pts was 52/65 (80%) with 25/47 (53%) MRD evaluable pts achieving MRD-neg post C1. The median RFS and OS was 17.6 and 26.6 mos, respectively. CR/CRp rate after C1 among pts who received mini-HCVD + ino in C1 was 100% (14/14) with 79% MRD-neg. On landmark analysis to the time to blina initiation, blina treated pts had similar RFS and trended for improved OS. A total of 19/65 (30%) had allo-SCT in CR1; all were MRD-neg prior to allo-SCT. Landmark analysis for OS based on time to allo-SCT (6 mos) favored SCT in CR1 (47.2 vs. 17.6 mos, p=0.04). Conclusions: Despite improvements in treatment options, CRLF2 overexpressed B-ALL continue to have inferior outcomes. Earlier initiation of targeted therapies might improve outcomes.

^#5 missed samples.