CHIP Associated with Poorer Outcomes in Lymphoma

The following article features coverage from the American Society of Hematology (ASH) 2018 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Clonal hematopoiesis of indeterminate potential (CHIP) that occurs as a result of somatic driver mutations in hematopoietic cells is associated with shorter overall survival (OS) and event-free survival (EFS) among patients with different subtypes of lymphoma, according to the results of a prospective registry study presented at the 2018 American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.¹

“CHIP, and particularly mutations in DNA damage response genes, are associated with increased mortality, which confirms findings from single center studies,” the investigators wrote.

Previous studies suggested that CHIP increases the risk of therapy-related myeloid neoplasms (tMN) and shorter survival after autologous stem cell transplantation (ASCT). The purpose of this study was to evaluate the effect of CHIP after ASCT in a nation-wide, population-based cohort.

The study included prospective data from 574 patients with lymphoma, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, Hodgkin lymphoma, peripheral T-cell lymphoma, and others from national Danish registries. Mobilized peripheral blood products were used to harvest DNA and RNA for targeted sequencing to assess over 95% of all mutations associated with CHIP. Mutations resulting in CHIP were more frequent among patients age 60 or older.

Somatic mutations meeting CHIP criteria were present in 33.3% of patients, and the most commonly mutated genes included NDMT3A (28%), TET2 (23%), PPM1D (16%), ASXL1 (10%), and TP53 (8%).

Shorter OS (P =.004), EFS (P =.03), an increased risk of biopsy-confirmed tMN (P =.03), and the likelihood of receiving blood transfusions after ASCT (P =.027) were significantly associated with the prevalence of CHIP.

Patients with mutations in DNA damage response genes, such as PPM1D and TP53, were particularly at risk of poorer outcomes, demonstrating significantly shorter OS and EFS (P <.0001 for both) and an increased risk of tMN (P =.01). These mutations were also associated with a significant increase in rates of secondary cancer (P =.004) and severe infection resulting in hospital admission (P =.01).

The authors concluded that CHIP is associated with mortality as well as other clinically relevant adverse outcomes, including severe infections, blood transfusions, and secondary cancers, and noted that “these data support the evaluation of CHIP for risk assessment in lymphoma patients before high-dose chemotherapy.”

Disclosures: This study was supported by Poseida Therapeutics. Please refer to the original abstract for a complete list of authors’ disclosures.

Reference

1. Husby S, Francesco F, Nielsen C, et al. Clinical impact of clonal hematopoiesis after autologous stem cell transplantation for lymphoma: a national population-based cohort study. Oral presentation at: American Society of Hematology 60th Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA. Abstract 607.