CML-102: Is Paraproteinemia More Prevalent in Patients with Chronic Myeloid Leukemia?

Abstract

Context: Though originating from different cell origins, several reports have described patients with the coexistence of chronic myeloid leukemia (CML) and paraproteinemias, mostly in patients treated with tyrosine kinase inhibitors (TKIs). Objective: Determine whether the prevalence of paraproteinemia in a large cohort of chronic phase (CP-) CML patients is higher than in the general population. Methods: This is a cross-sectional study among ambulatory CP-CML patients treated in a tertiary medical center. Between February 2019 and May 2021, consecutive CP-CML patients who consented to the study performed the following tests: serum protein electrophoresis & immunofixation (SPEP, IFIX), serum-free light chains (sFLC), and quantitative immunoglobulin (Ig) levels. Primary outcome was the prevalence of paraproteinemia among this cohort of CML patients. Secondary outcomes evaluated the correlations between paraproteinemia and various patient, disease, and treatment-related variables. Results: 100 patients, half males, with a median age of 63.5 years (range 26-91.6) were recruited for the study. The median time from CML diagnosis to enrollment was 6.3 years (range 0.1-23.5). Monoclonal (M-) protein was detected on SPEP and IFIX in 8 patients (8%), whose median age was 66.8 years (range 46-74). Among them, two patients also had an abnormal sFLC and elevated IgG or IgA levels and were diagnosed with IgG-kappa and IgA-kappa smoldering multiple myeloma (SMM), respectively. The other six patients had normal sFLCs and characteristics compatible with low-risk monoclonal gammopathy of undetermined significance (MGUS). Six patients with a detectable M-protein were treated with a TKI [imatinib (n=2), dasatinib (n=3), bosutinib (n=1)] and two were in treatment-free remission (TFR). All continue observation for their newly diagnosed paraproteinemia. None of the patients in our cohort was diagnosed with active MM. Conclusions: This is the largest study describing the prevalence of paraproteinemia among CML patients. We found the prevalence of MGUS in CP-CML patients (6%) to be higher than in the general population above the age of 50 (3.2%) and a non-negligible prevalence of SMM (2%). Based on these data, we recommend considering screening for paraproteinemia coexistence in CML patients. Further studies and extended follow-up are needed to elucidate the true clinical significance of our findings.