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
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
Shailender Bhatia, MD, of the University of Washington and Fred Hutchinson Cancer Center, discusses phase I/II results on the efficacy of nivolumab with or without ipilimumab in patients with recurrent or metastatic Merkel cell carcinoma. The study found that, for this rare and aggressive skin cancer, nivolumab showed clinical activity in advanced disease. However, these results from CheckMate 358 do not suggest an additional benefit with ipilimumab added to nivolumab (Abstract 9506).
The ASCO Post Staff
Shilpa Gupta, MD, of Cleveland Clinic, discusses the results from the EV-103 study and the unmet need for effective first-line therapies in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma. After nearly 4 years of follow-up, the trial findings showed that enfortumab vedotin-ejfv plus pembrolizumab continues to demonstrate promising survival trends with rapid and durable responses in this population (Abstract 4505).
The ASCO Post Staff
Jason J. Luke, MD, of the University of Pittsburgh Medical Center Hillman Cancer Center, discusses adjuvant pembrolizumab, which, in previous results, improved distant metastasis– and recurrence-free survival in patients with resected stage IIB or IIC melanoma vs placebo. After a median follow-up of 39.4 months, adjuvant pembrolizumab continued to show a benefit over placebo, with no new safety signals (Abstract LBA9505).
The ASCO Post Staff
Nirav N. Shah, MD, of the Medical College of Wisconsin, discusses the efficacy and safety of pirtobrutinib, a highly selective, noncovalent BTK inhibitor, studied for more than 3 years in the BRUIN trial. The results showed that the use of pirtobrutinib continues to have durable efficacy and a favorable safety profile in heavily pretreated patients with relapsed or refractory mantle cell lymphoma and prior BTK inhibitor therapy. Responses were observed in patients with high-risk disease features, including blastoid/pleomorphic variants, elevated Ki67 index, and TP53 mutations (Abstract 7514).
