On October 29, 2021, the FDA granted accelerated approval to asciminib (Scemblix; Novartis) for patients with Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, previously treated with ≥2 tyrosine kinase inhibitors (TKIs). The drug was also granted a full approval for adult patients with Ph+ CML in chronic phase with a T315I mutation.
“CML can be difficult to treat when currently available treatments fail patients, when treatment side effects cannot be tolerated, or sometimes both,” said Michael J. Mauro, MD, Hematologist and Program Leader, Myeloproliferative Neoplasms, Memorial Sloan Kettering Cancer Center, New York City, in a press release. “The addition of Scemblix into the CML treatment landscape gives us a novel approach to combat this blood cancer, helping address clinical challenges in patients struggling after switching to a second treatment, as well as in patients who develop the T315I mutation and face significantly worse outcomes.”
The approvals were based on data from the phase 3 ASCEMBL trial, which included patients with Ph+ CML in chronic phase who previously received ≥2 TKIs, and the phase 1 CABL001X2101 trial, which evaluated the use of asciminib in patients with Ph+ CML in chronic phase harboring a T315I mutation.
ASCEMBL included 233 patients randomized in a 2:1 ratio to receive asciminib at a twice-daily dose of 40 mg (N = 57) or bosutinib (Bosulif; Pfizer) at a once-daily dose of 500 mg (N = 76). Patients were stratified based on major cytogenetic response status, with treatment continuing until intolerable toxicity or treatment failure.
Results showed that asciminib elicited a major molecular response (MMR) rate of 25% (95% confidence interval [CI], 19%-33%) at 24 weeks compared with 13% (95% CI, 6.5%-23%) with bosutinib (95% CI, 2.2%-22%; P = .029). The complete cytogenetic responses produced at 24 weeks in the investigative and control arms were 41% (95% CI, 31%-51%) and 24% (95% CI, 14%-37%), respectively. At 48 weeks, the MMR rate was 29% in patients who received asciminib (95% CI, 22%-37%) compared with 13% in patients who received bosutinib (95% CI, 6.5%-23%). At a median follow-up of 20 months (day 1 to 36 months), the median duration of MMR had not yet been reached at any time.
Forty-five patients enrolled in the multicenter, open-label CABL001X2101 trial were administered asciminib at a twice-daily dose of 200 mg, with treatment continuing until intolerable toxicity or failure. Results showed that 42% of patients who received asciminib achieved MMR by 24 weeks (95% CI, 28%-58%) and 49% of patients achieved MMR rate by 96 weeks (95% CI, 34%-64%). The median duration of treatment was 108 weeks (2-215 weeks).
The most common (≥20%) adverse events (AEs) with asciminib were upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea. The most common laboratory abnormalities were decreased platelet counts, increased triglycerides, decreased neutrophil counts and hemoglobin, and increased creatine kinase, alanine aminotransferase, lipase, and amylase.
The recommended asciminib dose in patients with Ph+ CML in chronic phase who were previously treated with ≥2 TKIs is 80 mg taken orally once daily at approximately the same time each day or 40 mg twice daily at approximately 12-hour intervals. The recommended asciminib dose in patients with Ph+ CML in chronic phase with the T315I mutation is 200 mg orally twice daily at approximately 12-hour intervals.