Abstract
Background and Clinical Relevance: The association between acute myeloid leukemia (AML) and monoclonal gammopathy of undetermined significance (MGUS) is rare and likely coincidental, due to the similar epidemiology of these two blood disorders in older AML patients who are not eligible for intensive chemotherapy or aggressive treatment, as they can be excessively myelosuppressive. Such treatments include those containing venetoclax, an easy-to-use all-oral form of decitabine–cedazuridine (DEC-C), which is now available and approved for AML in addition to standard parenteral DNA methyltransferase inhibitors, which have been commonly used in routine clinical practice for about two decades in patients unsuitable for intensive chemotherapy (IC). Case Presentation: A 71-year-old woman developed a therapy-related acute myeloid leukemia (t-AML) seven years after the discovery of the plasma cell dyscrasia. She had carried an asymptomatic and non-progressing IgG-λ MGUS since 2019 while affected by breast cancer, which was cured with chemotherapy and radiotherapy. BM smear and trephine biopsy at the time of t-AML diagnosis showed 30% myelomonoblasts and 8% plasma cells, while SPEP showed the presence of 15 g/L of monoclonal protein. However, considering her age and other medical and personal history, the patient was found unsuitable for IC as well as venetoclax treatment because of the myelosuppressive effect of the therapy. Therefore, she received DEC-C oral monotherapy. After four DEC-C cycles, she achieved CR with hematological incomplete recovery (CRi). During DEC-C monotherapy, serum immunofixation (IF) and BM evaluations after 12 months of treatment showed gradual clearance of the IgG-λ paraprotein and BM plasma cells. Maintenance therapy with oral DEC-C is ongoing for 18 months after achieving CRi, without any signs of toxicity or infection. Conclusions: This report describes the first anecdotal case of t-AML responding to DEC-C with concomitant clearance of the paraprotein associated with MGUS.