How we manage multiple myeloma with clonal hematopoiesis of indeterminate potential (CHIP): a case report

Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by genetic alterations associated with hematologic neoplasms, posing clinical challenges in managing concurrent hematological malignancies. CHIP may complicate the treatment landscape due to its potential to influence disease progression and treatment response. We report a 73-year-old male with multiple myeloma (MM) harboring a CHIP PPM1D mutation, elucidating the complexities and therapeutic considerations in such cases.

After four cycles of cyclophosphamide, bortezomib, and dexamethasone therapy, he achieved a partial response, followed by complete hematologic response (CR) post eight cycles of lenalidomide, dexamethasone, and bortezomib therapy. Despite this, upfront autologous hematopoietic stem cell transplantation (HSCT) was initially deemed unsuitable due to positive PPM1D CHIP status. HSCT proceeded after aggressive relapse with clonal evolution but yielded short-lived response. Following failure of >4 lines of therapy, he received chimeric antigen receptor T (CAR-T) cell therapy (ciltacabtagene autoleucel) for salvage. This approach successfully induced remission, which was maintained for 6 months.

This case report highlights MM management complexities in CHIP presence, suggesting potential utility of HSCT and CAR-T cell therapy. Prospective studies are necessary to evaluate the safety and efficacy of these therapies in myeloma patients with concurrent CHIP, aiming to optimize treatment strategies and improve outcomes in this challenging clinical context.