ASCERTAIN: Real-world asciminib (ASC) effectiveness in patients (pts) with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL).

Abstract

6526 Background: ATP-competitive tyrosine kinase inhibitors (TKIs) in combination with chemoimmunotherapy have improved outcomes in Ph+ ALL; still, some pts relapse despite appropriate frontline therapy and have limited options. ASC is approved for Ph+ chronic myeloid leukemia in chronic phase. The ASC managed access program (MAP) allowed adults with Ph+ ALL refractory/resistant or intolerant to available treatment (Tx) to receive ASC as monotherapy or combination under individual request when the potential benefit outweighed the risk. Methods: This was a non-interventional, multi-country, retrospective chart review in eligible pts with Ph+ ALL aged ≥18 who were refractory/resistant or intolerant to available Tx and who received ≥1 dose of ASC within the MAP. Index date (date of first ASC administration) occurred between 1 March 2019 and 30 June 2023. Existing data were extracted from index date up to 13 months (mo), or until discontinuation, death or last visit, whichever occurred first. The primary endpoint was complete hematologic remission (CR) and CR with incomplete count recovery (CRi) anytime in the first 3 mo of Tx based on peripheral blood assessments. Results: A total of 37 pts were enrolled. At Tx start, 25 pts (67.6%) received ASC as monotherapy. Median ASC dose intensity was 400 mg/day (range 71.6–400.0). Overall, 23 pts (62.2%) achieved CR/CRi within 3 months (95% CI: 44.8, 77.5). Median duration of response was 7.4 mo. Median overall survival was 7.7 mo. Nineteen pts were assessed for minimal residual disease (MRD) at time of CR/CRi and 7 (36.8%) were MRD-. Of the 13 pts with T315I mutation, 10 achieved CR or CRi at any time during follow-up. Thirty-three pts (89.2%) permanently discontinued ASC; reasons for permanent discontinuation included disease progression (n=16) and adverse events (AEs, n=5). Any-grade Tx-emergent AEs were reported in 73.0% (Grade ≥3, 56.8%) of pts; the most common any-grade AE was neutropenia (21.6%). No new safety signals were observed. Most deaths (22/28) were Ph+ ALL related. Conclusions: Adults with Ph+ ALL that was relapsed, resistant/refractory or intolerant to previous Tx achieved high rates of CR/CRi with ASC as monotherapy or in combination with chemotherapy/immunotherapy, despite most pts being heavily pretreated and/or harboring poor prognosis markers (Table). The safety profile was consistent with previous studies. Results, while positive, should be cautiously interpreted given the retrospective nature of the study and heterogenous population. Pt baseline characteristics. Pts N=37 Median age (range), years 53 (19─84) Disease status (bone marrow blasts), %≥5%<5%Unknown 67.624.38.1 Prior treatment lines, %123≥4 2.732.421.643.2 Ponatinib pretreatment, % 94.6 T315I mutation, % 35.1 Reason for starting ASC, %RelapseSpecific mutationsResistanceIntoleranceOther 67.627.024.318.913.5