Clonal Hematopoiesis of Indeterminate Potential in Patients with Immunoglobulin Light Chain AL Amyloidosis

Immunoglobulin light chain (AL) amyloidosis is characterized by the deposition of misfolded monoclonal free light chains, with cardiac complications accounting for patients' mortality. Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with worse cardiovascular outcomes in the general population. Its significance in AL amyloidosis remains unclear. We collected clinical information and outcome data on 76 patients with a diagnosis of AL amyloidosis who underwent deep-targeted sequencing for myeloid neoplasia-associated mutations between April 2018 and August 2023. Variant allele fraction was set at 2% to call CHIP-associated mutations. CHIP mutations were present in AL amyloidosis patients at a higher frequency than age-matched control individuals. Sixteen patients (21%) had at least 1 CHIP mutation. DNMT3A was the most frequent mutation (7/16, 44%). Compared to patients without CHIP, patients with CHIP were enriched for the presence of t(11;14) (69% vs 25%, respectively, p = 0.004) and, for patients with renal involvement, a lower Palladini renal stage (p = 0.001). At a median follow-up of 32.5 months, the presence of CHIP was not associated with worse overall survival or major organ dysfunction progression-free survival. Larger studies and longer follow-up are needed to better define the impact of CHIP in patients with AL amyloidosis.