Clonal Hematopoiesis and Cardiovascular Disease in Patients With Multiple Myeloma Undergoing Hematopoietic Cell Transplant.

Importance: There is a paucity of information on the association between clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular disease (CVD) in patients with cancer, including those with multiple myeloma (MM) undergoing hematopoietic cell transplant (HCT), a population at high risk of developing CVD after HCT. Objective: To examine the association between CHIP and CVD in patients with MM and to describe modifiers of CVD risk among those with CHIP. Design, Setting, and Participants: This was a retrospective cohort study of patients with MM who underwent HCT between 2010 and 2016 at City of Hope Comprehensive Cancer Center in Duarte, California, and had pre-HCT mobilized peripheral blood stem cell (PBSC) products cryopreserved and accessible for CHIP analyses. The study team performed targeted panel DNA sequencing to detect the presence of CHIP (variant allele frequency 2% or more). Main Outcomes and Measures: The primary end point was the 5-year cumulative incidence and risk for developing de novo CVD (heart failure, coronary artery disease, or stroke) after HCT. Results: Of 1036 consecutive patients with MM (580 male [56%]; median age, 60.0 years) who underwent a first autologous HCT, 201 patients had at least 1 CHIP variant (19.4%) and 35 patients had 2 or more variants (3.4%). The 5-year incidence of CVD was significantly higher in patients with CHIP (21.1% vs 8.4%; P < .001) compared with those without CHIP; the 5-year incidence among those with 2 or more variants was 25.6%. In the multivariable model, CHIP was associated with increased risk of CVD (hazard ratio [HR], 2.72; 95% CI, 1.70-4.39), as well as of individual outcomes of interest, including heart failure (HR, 4.02; 95% CI, 2.32-6.98), coronary artery disease (HR, 2.22; 95% CI, 1.06-4.63), and stroke (HR, 3.02; 95% CI, 1.07-8.52). Patients who had both CHIP and preexisting hypertension or dyslipidemia were at nearly 7-fold and 4-fold increased risk of CVD, respectively (reference: no CHIP, no hypertension, or dyslipidemia). Conclusion and Relevance: CHIP was significantly and independently associated with risk of CVD in patients with MM undergoing HCT and may serve as a novel biologically plausible biomarker for CVD in this cohort. Patients with MM and both CHIP and cardiovascular risk factors had an exceptionally high risk of CVD. Additional studies are warranted to determine if cardiovascular preventive measures can reduce CHIP-associated CVD risk.

Identifying monoclonal gammopathy of undetermined significance from electronic health records.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Use of electronic health records may facilitate large-scale epidemiologic research to elucidate risk factors for the progression of MGUS to MM or other lymphoid malignancies. AIMS: We evaluated the accuracy of an electronic health records-based approach for identifying clinically diagnosed MGUS cases for inclusion in studies of patient outcomes/ progression risk. METHODS AND RESULTS: Data were retrieved from Kaiser Permanente Southern California's comprehensive electronic health records, which contain documentation of all outpatient and inpatient visits, laboratory tests, diagnosis codes and a cancer registry. We ascertained potential MGUS cases diagnosed between 2008 and 2014 using the presence of an MGUS ICD-9 diagnosis code (273.1). We initially excluded those diagnosed with MM within 6 months after MGUS diagnosis, then subsequently those with any lymphoid malignancy diagnosis from 2007 to 2014. We reviewed medical charts for 100 randomly selected potential cases for evidence of a physician diagnosis of MGUS, which served as our gold standard for case confirmation. To assess sensitivity, we also investigated the presence of the ICD-9 code in the records of 40 randomly selected and chart review-confirmed MGUS cases among patients with a laboratory report of elevated circulating monoclonal (M-) protein (a key test for MGUS diagnosis) and no subsequent lymphoid malignancy (as described above). The positive predictive value (PPV) for the ICD-9 code was 98%. All MGUS cases confirmed by chart review also had confirmatory laboratory test results. Of the confirmed cases first identified via M-protein test results, 88% also had the ICD-9 diagnosis code. CONCLUSION: The diagnosis code-based approach has excellent PPV and likely high sensitivity for detecting clinically diagnosed MGUS. The generalizability of this approach outside an integrated healthcare system warrants further evaluation.