On October 29, 2024, the Food and Drug Administration granted accelerated approval for asciminib (Scemblix, Novartis AG) for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in the chronic phase (CP).
Effectiveness and Safety
The effectiveness of asciminib for newly diagnosed Ph+ CML in chronic phase was assessed in ASC4FIRST (NCT04971226), a multicenter, randomized, active-controlled, open-label study. A total of 405 patients were randomized in a 1:1 ratio to receive either asciminib or investigator-selected tyrosine kinase inhibitors (IS-TKIs), including imatinib, nilotinib, dasatinib, or bosutinib.
The primary effectiveness endpoint was the major molecular response (MMR) rate at 48 weeks. At 48 weeks, the MMR rate was 68% (95% CI: 61, 74) in the asciminib group and 49% (95% CI: 42, 56) in the IS-TKIs group, resulting in a difference of 19% (95% CI: 10, 28), with a p-value of <0.001. In the imatinib cohort, the MMR rate was 69% (95% CI: 59, 78) for the asciminib group and 40% (95% CI: 31, 50) for the IS-TKIs group, resulting in a difference of 30% (95% CI: 17, 42, p-value <0.001).
Patients with newly diagnosed and previously treated Ph+ CML in chronic phase experienced the most prevalent adverse events (≥20%), including musculoskeletal pain, rash, exhaustion, upper respiratory tract infection, headache, abdominal discomfort, and diarrhea.
The predominant laboratory abnormalities (≥40%) in patients with newly diagnosed Ph+ CML in chronic phase included reduced lymphocyte count, reduced leukocyte count, reduced platelet count, reduced neutrophil count, and decreased corrected calcium levels.
The advised dosage of asciminib is 80 mg administered orally once daily at a consistent time or 40 mg taken orally twice daily at approximately 12-hour intervals.
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
