FDA Approves Asciminib for Chronic Myeloid Leukemia

The FDA granted accelerated approval to asciminib (Scemblix) for the treatment of patients with Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) in chronic phase who were previously administered 2 or more tyrosine kinase inhibitors (TKIs). The FDA also issued a full approval for the use of asciminib in patients with Ph-positive CML in chronic phase with a T315I mutation.¹

“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 Myeloproliferative Neoplasms Program leader at Memorial Sloan Kettering Cancer Center, in a press release.² “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-positive CML who previously received 2 or more TKIs, and the phase 1 CABL001X2101 trial, which evaluated the use of asciminib in patients with Ph-positive CML in chronic phase harboring a T315I mutation.

ASCEMBL included 233 patients randomized 2:1 to receive either asciminib at a twice-daily dose of 40 mg (n = 157) or bosutinib (Bosulif) at a once-daily dose of 500 mg (n = 76). Patients were stratified based on major cytogenetic response status, with treatment continued until intolerable toxicity or treatment failure.

The participants had a median age of 52 years (19-83 years of age) and 19% of patients were 65 years of age or older, with 2.6% of patients 75 years of age or older. Further, 52% of patients were female, 75% were White, and 81% had an ECOG performance status of 0.

Among these patients, 48% received 2 prior lines of treatment, 31% received 3 prior lines, 15% received 4 prior lines, and 6% received 5 or more prior lines. The median duration of treatment was 67 weeks (range, 0.1-162) in patients administered asciminib compared with 30 weeks in patients administered bosutinib.

The trial found that asciminib elicited a molecular response (MMR) rate of 25% (95% 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% (95% CI, 22%-37%) in patients administered asciminib compared with 13% (95% CI, 6.5%-23%) in patients administered bosutinib. At a median follow-up of 20 months (1 day to 36 months), the median duration of response had not yet been reached with MMR at any time.

The number of patients who discontinued asciminib because of toxicities was 3 times lower with asciminib at 7% compared with 25% among patients treated with bosutinib.

The most frequently reported adverse effects in the asciminib cohort included upper respiratory tract infections and musculoskeletal pain; decreased platelet and neutrophil counts, reduced hemoglobin; and increased triglycerides, creatine kinase, and alanine aminotransferase.

Forty-five patients enrolled in CABL001X2101 were administered asciminib at a twice-daily dose of 200 mg, with treatment continued until intolerable toxicity or failure.

The median age of study participants was 54 years (26-86 years of age), with 31% of patients 65 years of age and older and 9% of patients 75 years of age and older. Eighty percent of patients were male, 47% were White, and 73% had an ECOG performance status of 0. Among these patients, 18%, 31%, 36%, 13%, and 2.2%, respectively, were administered 1, 2, 3, 4, or 5 or more prior treatments.

The researchers found that 42% (95% CI, 28%-58%) of patients administered asciminib achieved MMR by 24 weeks and 49% of patients (95% CI, 34%-64%) achieved MMR by 96 weeks. The median duration of treatment was 108 weeks (2-215 weeks).

“The introduction of TKIs 20 years ago revolutionized treatment for CML; however, there remain many patients who do not respond adequately to at least two available treatments and often experience challenging side effects that add a burden to their daily lives,” said Lee Greenberger, chief scientific officer at The Leukemia & Lymphoma Society, in a press release. “The approval of Scemblix may offer hope to patients by addressing gaps in CML care.”²

References

1. Asciminib. Prescribing information. Novartis; 2021. Accessed October 29, 2021. https://bit.ly/3bllZws
2. FDA approves Novartis Scemblix (asciminib), with novel mechanism of action for the treatment of chronic myeloid leukemia. News release. Novartis. October 29, 2021. Accessed October 29, 2021. https://bit.ly/3bm9lNR