Publications by authors named "A R Mato"
Article Synopsis
- Bruton tyrosine kinase inhibitors (BTKis) like ibrutinib, used for lymphoid malignancies, can lead to new or worsening hypertension (HTN), raising concerns about optimal treatment methods.
- A study of 196 patients divided them into two groups: those with pre-existing HTN and those who developed it after starting BTKis; results showed different antihypertensive strategies were effective for each group.
- Patients with prior HTN benefited from a combination of β blockers and hydrochlorothiazide, while those with new HTN responded well to ACE inhibitors or ARBs combined with hydrochlorothiazide, suggesting a need for tailored treatments and further research.
Increasing use of covalent and noncovalent inhibitors of Bruton's tyrosine kinase (BTK) has elucidated a series of acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance mutations in BTK with distinct enzymatic activities, including some that impair BTK enzymatic activity while imparting novel protein-protein interactions that sustain B cell receptor (BCR) signaling. Furthermore, we describe a clinical-stage BTK and IKZF1/3 degrader, NX-2127, that can bind and proteasomally degrade each mutant BTK proteoform, resulting in potent blockade of BCR signaling.
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- Genomic profiling of blood cancers has improved our understanding of the genetic changes that drive these diseases and has helped create better tools for patient treatment planning.*
- Tumor-only sequencing methods often struggle to provide clear information on genetic variants, which can complicate clinical decisions for patient care.*
- The MSK-IMPACT Heme cohort offers a detailed analysis of genetic alterations by comparing tumor and normal DNA, revealing key mutation patterns and enhancing our ability to make precise genetic diagnoses.*
Article Synopsis
- Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) often struggle after failing treatment with covalent BTK inhibitors, prompting the need for new options like pirtobrutinib, a selective noncovalent BTK inhibitor designed to resume BTK inhibition.* -
- In a phase 1-2 trial involving 317 patients, 73.3% responded positively to pirtobrutinib, with a notable 82.2% response rate when including those showing partial responses with lymphocytosis; the median progression-free survival was reported at 19.6 months.* -
- Common side effects from pirtobrutinib treatment included infections (71%),