The Food and Drug Administration granted accelerated approval to pirtobrutinib (Jaypirca, Eli Lilly and Company) on December 1, 2023, for adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have undergone at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
The study looked at how well it worked in BRUIN (NCT03740529), a worldwide, open-label, single-arm, multicohort trial with 108 people who had CLL or SLL and had already had at least two other treatments, including a BTK inhibitor and a BCL-2 inhibitor. Patients underwent a median of 5 previous lines of therapy, with a range from 2 to 11. Seventy-seven percent of patients stopped using the previous BTK inhibitor due to refractory or worsening illness. The drug Pirtobrutinib was given orally at a dosage of 200 mg once a day and was maintained until disease progression or unacceptable toxicity occurred.
The primary efficacy metrics were the overall response rate (ORR) and duration of response (DOR), evaluated by an independent review committee based on the 2018 iwCLL criteria. The objective response rate (ORR) was 72% with a 95% confidence interval (CI) of 63% to 80%, and the median duration of response (DOR) was 12.2 months with a 95% CI of 9.3 to 14.7. All responses were incomplete.
The most frequent side effects (≥ 20%), not including laboratory-related terms, were fatigue, bruises, cough, musculoskeletal discomfort, COVID-19, diarrhea, pneumonia, stomach pain, dyspnea, bleeding, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities affecting more than 10% of patients included reduced neutrophil counts, anemia, and decreased platelet counts. 32% of patients experienced severe infections, with fatal infections reported in 10% of cases. The prescribing material include cautions and advisories for infections, bleeding, cytopenias, cardiac arrhythmias, and subsequent primary cancers.
The suggested pirtobrutinib dosage is 200 mg taken orally once a day until disease progression or intolerable effects.
View full prescribing information for Jaypirca.
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.
