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
Bobbie J. Rimel, MD, of Cedars-Sinai Medical Center, and Kathleen N. Moore, MD, of the Stephenson Oklahoma Cancer Center at the University of Oklahoma, discuss phase III results from the MIRASOL trial, which showed that mirvetuximab soravtansine-gynx prolonged overall survival vs investigator’s choice chemotherapy in patients with platinum-resistant ovarian cancer with high folate receptor-alpha expression. The findings suggest a new standard of care for this disease (Abstract LBA5507).
The ASCO Post Staff
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The ASCO Post Staff
Alicia K. Morgans, MD, MPH, and Praful Ravi, MRCP, MBBChir, both of Dana-Farber Cancer Institute, discuss an individual patient-data analysis of randomized trials from the ICECAP collaborative. A PSA nadir of ≥ 0.1 ng/mL within 6 months after radiotherapy completion was prognostic for prostate cancer–specific, metastasis-free, and overall survival in patients receiving radiotherapy plus androgen-deprivation therapy for localized prostate cancer. These findings may help identify patients for therapy de-escalation trials (Abstract 5002).
The ASCO Post Staff
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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).
