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
Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Karim Fizazi, MD, of Institut Gustave Roussy, University of Paris-Saclay, discuss findings from the TALAPRO-2 study, which showed that talazoparib plus enzalutamide improved radiographic progression–free survival over standard-of-care enzalutamide as first-line treatment for patients with metastatic castration-resistant prostate cancer and HRR gene alterations. This regimen also delayed the time to deterioration in global health status and quality of life (Abstract 5004).
The ASCO Post Staff
Lisa M. DeAngelis, MD, and Ingo K. Mellinghoff, MD, both of Memorial Sloan Kettering Cancer Center, discuss findings from the INDIGO trial showing that the IDH1/2 inhibitor vorasidenib improves progression-free survival for patients with residual or recurrent grade 2 glioma with an IDH1/2 mutation. These data demonstrate the clinical benefit of vorasidenib in this patient population for whom chemotherapy and radiotherapy are being delayed.
The ASCO Post Staff
Allison Betof Warner, MD, PhD, of Stanford University Medical Center, and Adnan Khattak, MBBS, FRACP, PhD, of Australia’s Hollywood Private Hospital & Edith Cowan University, discuss the use of the mRNA-4157 vaccine in combination with pembrolizumab as adjuvant therapy for resected high-risk melanoma, which prolonged distant metastasis–free survival compared with pembrolizumab alone. These results provide further evidence that a personalized neoantigen approach is potentially beneficial (Abstract LBA9503).
The ASCO Post Staff
Guillermo Garcia-Manero, MD, of The University of Texas MD Anderson Cancer Center, discusses phase III findings from the COMMANDS trial. Compared with epoetin alfa, luspatercept improved red blood cell transfusion independence and erythroid response, as well as the duration of response in erythropoiesis-stimulating agent–naive, transfusion-dependent patients with lower‐risk myelodysplastic syndromes (Abstract 7003).
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).
