Remarkable stability in clonal hematopoiesis involving leukemia‐driver genes in patients without underlying myeloid neoplasms

Abstract

Herein, we report the first case of PBL treated with the anti-PD1 monoclonal antibody pembrolizumab at standard doses approved for use in patients with relapsed or refractory Hodgkin lymphoma. The expression of PDL1 in the malignant cells and the tumor-associated macrophages served as the biological basis for our intervention. No treatment intervention is without potential toxicity, however. Our patient experienced a number of adverse events probably related to PD1 blockade. Cardiomyopathy with LVEF at 10% developed after 18 cycles of pembrolizumab therapy prompting permanent discontinuation. Cardiomyopathy with left ventricular systolic dysfunction appears to be a late adverse event associated with PD1 blocking agents. 8 Fortunately, the cardiomyopathy improved after drug discontinuation.Our experience suggest that anti-PD1 monoclonal antibody therapy could be effective in the management of patients with PBL with PDL1 expression, especially in patients who might not be optimal candidates for combination chemotherapy or autologous stem cell transplantation.

Molecular Pathways in Clonal Hematopoiesis: From the Acquisition of Somatic Mutations to Transformation into Hematologic Neoplasm

“…For instance, DNMT3A and JAK2 mutations appear throughout life, while splicing factor and IDH1/2 mutations tend to arise in individuals older than 70 years of age, suggesting that cell-extrinsic age-related factors may contribute to their acquisition [ 28 , 29 , 56 , 95 ]. Interestingly, studies suggest that DNMT3A mutated clones have relatively stable VAFs over the course of several years and even decelerate in older age, while TET2 mutated clones may not, highlighting the complexity of CH evolutionary dynamics [ 29 , 115 , 116 , 117 ].…”

Single cell multiomic analyses reveal divergent effects ofDNMT3AandTET2mutant clonal hematopoiesis in inflammatory response

“…[10][11][12] CH has been associated with a low, but increased risk of hematological neoplasms and an increased all-cause mortality, largely due to cardiovascular disease and inflammation associated endothelial dysfunction. [11][12][13][14] In a large cohort of 515 patients with COVID-19, CH was associated with severe COVID-19 outcomes, including increased mortality. 15 However, majority of these patients had underlying visceral malignancies, with several getting chemo-/ immunotherapy, and except for a nonsignificant trend with PPM1D mutations, there were no clear mutational associations detected.…”