On October 29, 2021, the oral kinase inhibitor asciminib was granted accelerated approval for adults with Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase previously treated with at least two tyrosine kinase inhibitors and regular approval for adults with Philadelphia chromosome–positive CML in chronic phase with T315I mutation.¹

Supporting Efficacy Data

Approval of asciminib in patients previously treated with a tyrosine kinase inhibitor for Philadelphia chromosome–positive CML in chronic phase was based on findings in the ASCEMBL study (ClinicalTrials.gov identifier NCT03106779). In this trial, 233 patients were randomly assigned 2:1 to receive asciminib at 40 mg twice daily (n = 157) or bosutinib at 500 mg once daily (n = 76). Major molecular response at 24 weeks was achieved in 25% (95% confidence interval [CI] = 19%–33%) vs 13% (95% CI = 6.5%–23%) of patients (P = .029). After a median follow-up of 20 months, the median duration of major molecular response was not reached.

Approval of asciminib in patients with Philadelphia chromosome–positive CML in chronic phase with T315I mutation was based on findings from the CABL001X2101 study (NCT02081378). In this trial, 45 patients received asciminib at 200 mg twice daily. Major molecular response was achieved by 24 weeks in 42% (95% CI = 28%–58%) and by 96 weeks in 49% (95% CI = 34%–64%) of patients.

How It Is Used

The recommended dose in patients with Philadelphia chromosome–positive CML in chronic phase who were previously treated with at least two tyrosine kinase inhibitors is 80 mg once daily or 40 mg twice daily. The recommended dose in patients with Philadelphia chromosome–positive CML in chronic phase who have T315I mutation is 200 mg twice daily. Treatment is continued if clinical benefit is observed or until unacceptable toxicity.

Product labeling provides instructions on dosage modification, including dose reduction, for adverse reactions including thrombocytopenia or neutropenia, asymptomatic amylase or lipase elevation, and grade ≥ 3 nonhematologic adverse reactions. Product labeling provides instructions on potential concomitant use with strong CYP3A4 inhibitors, itraconazole oral solution containing hydroxypropyl-β-cyclodextrin, certain CYP3A4 substrates, CYP2C9 substrates, and certain P-glycoprotein substrates.

Safety Profile

Among patients receiving asciminib in ASCEMBL (40 mg twice daily) and CABL001X2101 (200 mg twice daily), the most common adverse events of any grade (≥ 20%) were upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea. The most common laboratory abnormalities of any grade were decreased platelets, neutrophils, and hemoglobin and increased triglycerides, creatine kinase, alanine aminotransferase, lipase, and amylase.

In ASCEMBL, serious adverse events occurred in 15% of patients, most commonly pyrexia (1.9%). Adverse events led to discontinuation of treatment in 7%, most commonly because of thrombocytopenia (3.2%). Fatal adverse events occurred in two patients (mesenteric artery thrombosis and ischemic stroke).

In CABL001X2101, serious adverse events occurred in 23%, most commonly abdominal pain, vomiting, and pneumonia (4.2% each). Adverse events led to discontinuation of treatment in 10%, most commonly because of elevated pancreatic enzymes (2.1%).

Asciminib has warnings/precautions for myelosuppression, pancreatic toxicity, hypertension, cardiovascular toxicity, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving asciminib. 

REFERENCE

1. Scemblix (asciminib) tablets prescribing information, Novartis, Revised October 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215358s000Orig1lbl.pdf. Accessed November 18, 2021.