Catherine C. Coombs, MD, on B-Cell Malignancies and Long-Term Safety of Pirtobrutinib
2023 ASCO Annual Meeting
Catherine C. Coombs, MD, of the University of California, Irvine, discusses prolonged pirtobrutinib therapy, which continues to demonstrate a safety profile amenable to long-term administration at the recommended dose without evidence of new or worsening toxicity signals. The safety and tolerability observed in patients on therapy for 12 months or more were similar to previously published safety analyses of all patients enrolled, regardless of follow-up (Abstract 7513).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Catherine C. Coombs:
BTK has proven to be an invaluable target of inhibition for the treatment of a number of B-cell malignancies. However, the use of BTK inhibitors is dependent upon their continuous administration. Therefore, safety and tolerability are paramount importance to maintain maximal efficacy. In this abstract, we reviewed the long-term safety data of Pirtobrutinib from the Phase 1/2 BRUIN trial. The trial design enrolled patients with a number of B-cell malignancies. The entire safety population was over 700 patients. However, in this post-hoc analysis, we reviewed the patients on treatment for over a year, which amounted to 326 patients. As one would expect, this population was enriched for patients with the more chronic B-cell malignancies, and so the largest population was CLL and SLL though there were about 40 patients with mantle cell lymphoma and Waldenström's macroglobulinemia. The safety aspects that were reviewed included all of the common side effects from this drug, which fortunately were very uncommon, especially grade three or higher AEs.
In reviewing treatment exposure adjusted AE rates, what we determined was that in comparing patients on the drug for over a year compared to the entire safety population, there does not appear to be an increased risk in toxicity for patients that are on the drug for longer periods of time. This is further supported by the low incidences of discontinuation for the drug, especially in those patients who were on the drug for over a year where only 1.2% of patients discontinued due to side effects. In addition, regarding the class effects of BTK inhibitors that we worry about, the incidences of atrial fibrillation, bleeding, and hypertension were all extremely low and did not suggest a temporal relationship to Pirtobrutinib. In conclusion, we can see that now with long-term administration of Pirtobrutinib, this drug is exquisitely safe and can inhibit its target, BTK, for maximal benefit to our patients with these malignancies.
The ASCO Post Staff
Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill, and Dennis J. Slamon, MD, PhD, of the University of California, Los Angeles, discuss phase III study findings on ribociclib plus endocrine therapy as adjuvant treatment in patients with hormone receptor–positive, HER2-negative early breast cancer. When added to standard-of-care endocrine therapy, ribociclib improved invasive disease–free survival with a well-tolerated safety profile (Abstract LBA500).
The ASCO Post Staff
Amer Methqal Zeidan, MBBS, MHS, of Yale University and Yale Cancer Center, discusses phase III findings on the first-in-class telomerase inhibitor imetelstat, which was given to patients with heavily transfusion-dependent non-del(5q) lower-risk myelodysplastic syndromes that are resistant to erythropoiesis-stimulating agents. Imetelstat resulted in a significant and sustained red blood cell (RBC) transfusion independence in 40% of these heavily transfused patients. The response was also durable and accompanied by an impressive median hemoglobin rise of 3.6 g/dL, and seen in patients with and without ring sideroblasts. Importantly, reduced variant allele frequency was observed in the most commonly mutated myeloid genes which correlated with duration of transfusion independence and hemoglobin rise, therefore suggesting a disease-modifying potential of this agent (Abstract 7004).
The ASCO Post Staff
Cathy Eng, MD, of Vanderbilt-Ingram Cancer Center, and Thejus Jayakrishnan, MD, of the Cleveland Clinic Taussig Cancer Institute, discuss significant differences in the citrate cycle, a core pathway of cellular metabolism associated with colorectal cancer. Metabolomic differences impacted by environmental exposures (arginine biosynthesis and dietary red meat) were also noted, suggesting possible links with younger age of onset in this disease (Abstract 3510).
The ASCO Post Staff
Narjust Florez, MD, of Dana-Farber Cancer Institute, and Filippo Gustavo Dall’Olio, MD, of Institut Gustave Roussy, discuss circulating tumor DNA tumor fraction, and its link to survival in patients with advanced non–small cell lung cancer (NSCLC) treated with maintenance durvalumab in the UNICANCER SAFIR02-Lung/IFCT1301 trial. Tumor fraction was positive in 16% of patients randomly assigned to receive durvalumab in the study. This population seems to have a limited benefit from maintenance durvalumab after induction chemotherapy (Abstract 2516).
The ASCO Post Staff
Aaron T. Gerds, MD, of Cleveland Clinic Taussig Cancer Institute, talks about treating the anemia many patients with myelofibrosis experience because of JAK inhibitor therapy. The ACE-536-MF-001 study showed that luspatercept improved anemia and transfusion burden in this population, with a safety profile consistent with that in previous studies (Abstract 7016).
