Combination Treatment Is Tolerable in Adults with BCR-ABL1-Positive ALL, Blast Phase CML

Asciminib in combination with dasatinib and prednisone is feasible and tolerable in adult patients with BCR-ABL1-positive acute lymphoblastic leukemia (ALL) and blast phase chronic myeloid leukemia (CML), according to a recent study.

Led by Marlise Luskin, MD, of the Dana-Farber Cancer Institute, the investigator-initiated, phase I study determined the maximum tolerated dose/recommended phase II dose of asciminib with dasatinib and prednisone.

Fourteen patients received 140 mg/day of dasatinib and 60 mg/m²/day of prednisone on days one-24, while asciminib was administered in escalating doses in a 3+3 design (DL1: 40 mg; DL2: 80 mg; DL3: 160 mg). Two patients at DL3 developed grade 3 amylase elevation, and one patient at DL3 developed grade 3 lipase elevations.

Because dose-limiting toxicity (DLT) was experienced at DL3, the study deescalated to DL2, and four additional patients enrolled at DL2 without experiencing a DLT. Therefore, asciminib at 80 mg/day was determined to be the recommended phase II dose.

Next, 11 patients were enrolled in an expansion cohort. The rates of molecular response among all evaluable patients after three cycles were 58.3% for measurable residual disease (MRD) 3.0, and 25% for MRD 4.0. Meanwhile, patients with ALL treated with the recommended phase II dose (80 mg/day) achieved molecular response rates after three cycles of 78.6% for MRD 3.0 and 42.9% for MRD 4.0.

“High rates of molecular response and bridging to transplant highlight encouraging preliminary activity,” researchers concluded.

Reference

Luskin M, Murakami M, Keating J, et al. A phase I study of asciminib (ABL001) in combination with dasatinib and prednisone for BCR-ABL1-positive ALL and blast phase CML in adults. Abstract #965. Presented at the 65th ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.