Clinical outcomes and evolution of clonal hematopoiesis in patients with newly diagnosed multiple myeloma.

Clonal hematopoiesis (CH) at time of autologous stem cell transplant (ASCT), has been shown to be associated with decreased overall survival (OS) and progression-free survival (PFS) in multiple myeloma (MM) patients not receiving immunomodulatory drugs (IMiDs). However, the significance of CH in newly diagnosed patients, including transplant-ineligible patients, and its effect on clonal evolution during MM therapy, has not been well studied. Using our new algorithm to differentiate tumor and germline mutations from CH, we detected CH in ~10% of 986 MM patients from the CoMMpass cohort (40/529 transplanted and 59/457 non-transplanted patients). CH was associated with increased age, risk of recurrent bacterial infections and cardiovascular disease. CH at time of MM diagnosis was not associated with inferior OS or PFS regardless of undergoing ASCT, and all patients benefited from IMiD-based therapies, irrespective of the presence of CH. Serial sampling of 52 patients revealed the emergence of CH over a median of 3 years of treatment, increasing its prevalence to 25%, mostly with DNMT3A mutations.