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Incidence of venous thromboembolism (VTE) varies across different regimens in newly diagnosed multiple myeloma (NDMM) patients. Limited data exist on the use of direct oral anticoagulants as thromboprophylaxis in the setting of haematologic malignancies, specifically multiple myeloma. In this retrospective study of 305 NDMM patients, VTE rates in those treated with carfilzomib, lenalidomide, dexamethasone (KRD) + aspirin (ASA), bortezomib, lenalidomide, dexamethasone (RVD) + ASA, and KRD + rivaroxaban were statistically significant, 16·1%, 4·8%, and 4·8%, respectively. The findings confirm a higher incidence of VTE when using KRD induction compared to RVD induction and reveal that the use of low-dose rivaroxaban thromboprophylaxis can mitigate this risk without an observable increase in bleeding rates.

Sustained minimal residual disease (MRD) negativity is associated with long-term survival in multiple myeloma (MM). The gut microbiome is affected by diet, and in turn can modulate host immunity, for example through production of short-chain fatty acids including butyrate. We examined the relationship of dietary factors, stool metabolites, and microbial diversity with sustained MRD negativity in patients on lenalidomide maintenance. At 3 months, higher stool butyrate concentration (p=0.037), butyrate producers (p=0.025) and α-diversity (p=0.0035) were associated with sustained MRD-negativity. Healthier dietary proteins, (from seafood and plants), correlated with butyrate at 3 months (p=0.009) and sustained MRD-negativity (p=0.05). Consumption of dietary flavonoids, plant nutrients with antioxidant effects, correlated with stool butyrate concentration (anthocyanidins p=0.01, flavones p=0.01, and flavanols p=0.02). This is the first study to demonstrate an association between a plant-based dietary pattern, stool butyrate production and sustained MRD-negativity in MM; providing rationale to evaluate a prospective dietary intervention.Statement of SignificanceWe demonstrate an association between diet, the gut microbiome, and sustained MRD-negativity in MM. A healthy diet, with adequate plant and seafood protein, and containing flavonoids, associates with stool diversity, butyrate production and sustained MRD-negativity. These findings suggest dietary modification should be studied to enhance myeloma control.Key PointsIn MM on lenalidomide maintenance, stool butyrate concentration at 3 months was associated with higher rates of MRD negativity at 12 months.Increased seafood and plant proteins, dietary flavonoids, and diversity of dietary flavonoids correlated with stool butyrate concentrations.

Multiple myeloma (MM) progression is characterized by the seeding of cancer cells in different anatomic sites. To characterize this evolutionary process, we interrogated, by whole genome sequencing, 25 samples collected at autopsy from 4 patients with relapsed MM and an additional set of 125 whole exomes collected from 51 patients. Mutational signatures analysis showed how cytotoxic agents introduce hundreds of unique mutations in each surviving cancer cell, detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature. Thus, a unique, single-cell genomic barcode can link chemotherapy exposure to a discrete time window in a patient's life. We leveraged this concept to show that MM systemic seeding is accelerated at relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high-dose melphalan therapy and autologous stem cell transplant.

Multiple myeloma (MM) progression is characterized by the seeding of cancer cells in different anatomic sites. To characterize this evolutionary process, we interrogated, by whole genome sequencing, 25 samples collected at autopsy from 4 patients with relapsed MM and an additional set of 125 whole exomes collected from 51 patients. Mutational signatures analysis showed how cytotoxic agents introduce hundreds of unique mutations in each surviving cancer cell, detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature. Thus, a unique, single-cell genomic barcode can link chemotherapy exposure to a discrete time window in a patient′s life. We leveraged this concept to show that MM systemic seeding is accelerated at relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high-dose melphalan therapy and autologous stem cell transplant., In multiple myeloma, disease progresses via seeding to different anatomic sites and clonal expansion. Here, utilising autopsy material, the authors show that systemic seeding accelerates at relapse following treatment.