Nirav N. Shah, MD, on Mantle Cell Lymphoma: Follow-up Data on Pirtobrutinib in Pretreated Disease
2023 ASCO Annual Meeting
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).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Nirav N. Shah:
So mantle cell lymphoma is a disease that sort of is felt to be a relapsing remitting disease, which means that most patients are going to relapse in their lifetime. Now, while we have very, very good therapies for relapse mantle cell, which generally include covalent BTK inhibitors. For those patients who progress after covalent BTK inhibitors, options are limited. We have treatments like CAR T-cell therapy, but not all patients are healthy enough, fit enough, or are in an area where CAR T-cell therapy is accessible. So pirtobrutinib was studied as part of the BRUIN trial to look specifically at patients with B-cell malignancies. And the data being reported is looking at the cohort of patients with mantle cell lymphoma who received this drug in a relapsed refractory setting. Unlike other BTK inhibitors pirtobrutinib is a non-covalent reversible inhibitor showing that it has a different mechanism of action than the BTK inhibitors that are currently being used in the second line setting.
As part of the BRUIN study, whether or not you had prior BTK exposure was not an exclusion, and so actually the majority of patients who received pirtobrutinib, 90 of them, actually had prior BTK exposure, which is an unmet need in mantle cell lymphoma. Despite seeing a different BTK inhibitor, first, the overall response rate with pirtobrutinib was 58% in this heavily pretreated group, which is really just exciting to have another oral agent be effective in that patient population. Not only was it effective, but there were also durable responses. And so now in this sort of two year long term follow-up, we know that the median duration of response for those patients who were responding to therapy was 18 months, and the median overall survival was nearly 2 years.
This data actually led to this drug now being FDA approved and in this clinical setting and available, and part of that is because the safety profile that's demonstrated in the BRUIN study in this patient population was actually quite favorable. The toxicities were low and the traditional BTK toxicities, things like atrial fibrillation, hypertension, and bleeding were actually seen at very low rates, such that may occur actually in a general patient population.
In conclusion, I think that pirtobrutinib represents a novel mechanism of action in inhibiting the BTK pathway and allowing patients that have failed other covalent BTK inhibitors to continue receiving an oral medication that has now shown incredible efficacy, safety, and durability.
The ASCO Post Staff
Carmen E. Guerra, MD, MSCE, of the University of Pennsylvania Abramson Cancer Center, discusses three key abstracts presented at ASCO: strategies to increase accrual of underrepresented populations in Alliance NCTN trials, how patient-clinician education can strengthen partnerships and improve diversity in breast and lung cancer trials, and mediators of racial and ethnic inequities in clinical trial participation among U.S. patients with cancer from 2011 to 2022 (Abstracts 6509, 6510, 6511).
The ASCO Post Staff
Arlene O. Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center, discusses phase III findings showing that for patients with advanced or metastatic urothelial carcinoma and FGFR alteration who already had been treated with a PD-(L)1 inhibitor, erdafitinib significantly improved overall and progression-free survival, as well as overall response rate, compared with investigator’s choice of chemotherapy (LBA4619).
The ASCO Post Staff
Arlene O. Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center, discusses the combination of erdafitinib and cetrelimab, which demonstrated clinically meaningful activity and was well tolerated in cisplatin-ineligible patients with metastatic urothelial carcinoma and fibroblast growth factor receptor alterations (Abstract 4504).
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
Jennifer A. Woyach, MD, of The Ohio State University Comprehensive Cancer Center, discusses results of a phase III study showing that progression-free survival with ibrutinib plus obinutuzumab plus venetoclax is not superior to ibrutinib plus obinutuzumab for treatment-naive older patients with chronic lymphocytic leukemia (CLL) in the setting of the COVID-19 pandemic. Long-term follow-up will determine whether there are advantages to obinutuzumab plus venetoclax, with special attention to measurable residual disease and therapy discontinuation (Abstract 7500).