Explore the vast range of titles available.

Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials.

Background Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment‐related toxicities and inferior overall survival (OS) among adults with solid malignancies. However, the association between LSMM and treatment‐related toxicities among adults with haematologic malignancies remains unclear. Methods Using a pre‐published protocol (CRD42020197814), we searched seven bibliographic databases from inception to 08/2021 for studies reporting the impact of LSMM among adults ≥18 years with a known haematologic malignancy. The primary outcome of interest was OS, and secondary outcomes included progression free survival (PFS) and non‐relapse mortality (NRM). These effect sizes were quantified in terms of hazards ratio (HR) along with 95% confidence interval (CI) and pooled across studies using a DerSimonian–Laird random‐effects model. Heterogeneity was assessed using the Cochran's Q and the I2 statistic. All hypothesis testing was two‐sided with an alpha of 0.05. Results Of 3791 studies screened, we identified 20 studies involving 3468 patients with a mean age of 60 years; 44% were female and the most common malignancy was diffuse large B‐cell lymphoma (42%). Most studies measured muscle mass using single slice computed tomography imaging at the L3 level. The presence of LSMM was associated with worse OS (pooled HR = 1.81, 95% CI = 1.48–2.22, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 60.4%), PFS (pooled HR = 1.61, 95% CI = 1.28–2.02, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 66.0%). Similarly, LSMM was associated with worse NRM (HR = 1.72, 95% CI = 1.34–2.22, P < 0.001) with little evidence of heterogeneity (Cochran's Q, I2 = 0.0%). Conclusions LSMM is associated with worse survival outcomes among adults with haematologic malignancies. Further research into understanding the underlying mechanism of this association and mitigating the negative effects of LSMM among adults with haematologic malignancies is needed.

Autologous stem cell transplantation (ASCT) has been the prime consolidative strategy to increase the depth and duration of response in newly diagnosed multiple myeloma (NDMM), albeit with short- and long-term toxicities. Minimal residual disease (MRD) is an important early response endpoint correlating with clinically meaningful outcomes and may be used to isolate the effect of ASCT. We report the impact of ASCT on MRD burden and generate a benchmark for evaluation of novel treatments as consolidation. We collected MRD by next generation sequencing (NGS; clonoSEQ®) post induction and post-ASCT in consecutive patients ( N  = 330, quadruplet, N  = 279; triplet, N  = 51). For patients receiving quadruplets, MRD < 10 −5 post-induction was 29% (MRD < 10 −6 15%) increasing to 59% post-ASCT (MRD < 10 −6 45%). Among patients with MRD > 10 −5 post-induction, ASCT lowered the MRD burden>1 log 10 for 69% patients. The use of quadruplet induction (vs. triplet) did not reduce the effect of ASCT on MRD burden. Reduction in MRD burden with ASCT was most pronounced in patients with high-risk chromosome abnormalities. This dataset provides granular data to delineate the impact of ASCT on MRD as legacy consolidative strategy in NDMM and provides an important benchmark for evaluation of efficacy of TCRT as experimental consolidative strategy.

Quadruplet induction, autologous hematopoietic cell transplant (AHCT), and measurable residual disease (MRD) response‐adapted consolidation yield an unprecedented depth of response in newly diagnosed multiple myeloma. Patients treated on MASTER (NCT03224507) ceased therapy and entered active surveillance (MRD‐SURE) after achieving MRD negativity. This study characterizes quantitative changes in the immunoglobulin (Ig) gene repertoire by next‐generation sequencing and serum gamma globulin levels. Quadruplet therapy leads to profound hypogammaglobulinemia and reduction in the Ig gene repertoire. Immune reconstitution (IR) is delayed in patients who received post‐AHCT consolidation compared to those who do not. Eighteen months after treatment cessation, there was no statistically significant difference between the groups.

Abstract Association of immunoglobulin isotypes with survival in the context of modern prognostic factors has not been determined. We utilized the Flatiron Health Electronic Health Record database and identified 8468 MM patients. Compared to IgG MM, patients with IgA MM were more likely to have ISS-III, anemia, and t(4;14), and light chain (LC) MM had higher renal dysfunction and t(11;14). IgA and LC MM patients have an inferior OS. The adverse prognostic impact of IgA and LC isotypes on OS persisted even after adjustment for variables impacting outcomes and likely suggests their unique biology beyond the presence of adverse prognostic factors.

Background Obesity is an established modifiable risk factor for multiple myeloma (MM). However, associations of obesity and MM risk in Black populations, for whom obesity and MM are more common, is less clear. Methods Using participants enrolled in the Integrative Molecular And Genetic Epidemiology study, we evaluated the association of anthropometric traits with MM risk overall, stratified by race and sex. Among cases, we assessed the association of BMI with the presence of myeloma-defining events. Results We observed an 18% increase in MM risk for every 5 kg/m 2 increase in usual adult BMI. Participants with severe obesity (BMI ≥ 40 kg/m 2 ) had the highest risk compared to those with a normal usual adult BMI (18.5–24.9 kg/m 2 ; OR = 1.87, 95% CI 1.25–2.80), particularly among Black men (OR = 3.94, 95% CI 0.90–17.36). Furthermore, MM cases with overweight/obesity (BMI ≥ 25 kg/m 2 ) were more likely to present at diagnosis with low renal function (OR = 1.62, 95% CI 1.09–2.40), deletion 13q (OR = 1.73, 95% CI 1.08–2.76) and lytic lesions or compression fractures (OR = 2.39, 95% CI 0.82–7.01) and less likely to present with severe diffuse osteopenia (OR = 0.51, 95% CI 0.31–0.81). Conclusions Findings underscore the importance of obesity as a modifiable risk factor for MM, particularly in high-risk populations, and for the clinical presentation of disease.