Gertz, Morie A.

BackgroundSarcopenia increases with age and is associated with poor survival outcomes in patients with cancer. By using a deep learning–based segmentation approach, clinical computed tomography (CT) images of the abdomen of patients with newly diagnosed multiple myeloma (NDMM) were reviewed to determine whether the presence of sarcopenia had any prognostic value.MethodsSarcopenia was detected by accurate segmentation and measurement of the skeletal muscle components present at the level of the L3 vertebrae. These skeletal muscle measurements were further normalized by the height of the patient to obtain the skeletal muscle index for each patient to classify them as sarcopenic or not.ResultsThe study cohort consisted of 322 patients of which 67 (28%) were categorized as having high risk (HR) fluorescence in situ hybridization (FISH) cytogenetics. A total of 171 (53%) patients were sarcopenic based on their peri‐diagnosis standard‐dose CT scan. The median overall survival (OS) and 2‐year mortality rate for sarcopenic patients was 44 months and 40% compared to 90 months and 18% for those not sarcopenic, respectively (p < .0001 for both comparisons). In a multivariable model, the adverse prognostic impact of sarcopenia was independent of International Staging System stage, age, and HR FISH cytogenetics.ConclusionsSarcopenia identified by a machine learning–based convolutional neural network algorithm significantly affects OS in patients with NDMM. Future studies using this machine learning–based methodology of assessing sarcopenia in larger prospective clinical trials are required to validate these findings.

Abstract Overall Survival estimates from diagnosis are valuable for guiding treatment, but do not consider the years already survived. Conditional survival (CS) provides dynamic survival predictions over time. This study was conducted to estimate CS at 1–8 years from diagnosis and the impact of baseline prognostic factors on CS in multiple myeloma (MM) patients. This is a retrospective study including 2556 MM patients diagnosed between 2004–2019. CS (t|s) was defined as the probability of surviving t years given survival of s years. Median age was 64 years. Median follow-up was 6.2 years and median overall survival from diagnosis was 7.5 years. The 5-year CS estimates at s = 0, 1, 2, 3, and 5 years were 0.64, 0.61, 0.61, 0.61, and 0.58, respectively. On multivariate analysis, age ≥ 65 and proteasome inhibitor + immunomodulatory-based induction were associated with decreased survival and increased survival, respectively, retained at 5 years. The adverse impact of 1q gain/amplification, high-risk IgH translocation, and ISS-3 was significant at 1 and 3 years but not 5 years. Chromosome 17 abnormality was associated with decreased survival only at 1 year. Among MM patients, 5-year CS was stable at 1–5 years from diagnosis. The prognostic impact of high-risk cytogenetic factors decreased with additional years survived.

AbstractPatients with multiple myeloma (MM) have a lower efficacy from COVID‐19 vaccination and a high rate of mortality from COVID‐19 in hospitalized patients. However, the overall rate and severity of COVID‐19 infection in all settings (including non‐hospitalized patients) and the independent impact of plasma cell‐directed therapies on outcomes needs further study. We reviewed the medical records of 9225 patients with MM or AL amyloidosis (AL) seen at Mayo Clinic Rochester, Arizona, and Florida between 12/01/2019 and 8/31/2021 and identified 187 patients with a COVID‐19 infection (n = 174 MM, n = 13 AL). The infection rate in our cohort was relatively low at 2% but one‐fourth of the COVID‐19 infections were severe. Nineteen (10%) patients required intensive care unit (ICU) admission and 5 (3%) patients required mechanical ventilation. The mortality rate among hospitalized patients with COVID‐19 was 22% (16/72 patients). Among patients that were fully vaccinated at the time of infection (n = 12), two (17%) developed severe COVID‐19 infection, without any COVID‐related death. On multivariable analysis, treatment with CD38 antibody within 6 months of COVID‐19 infection [Risk ratio (RR) 3.6 (95% CI: 1.2, 10.5), p = .02], cardiac [RR 4.1 (95% CI: 1.3, 12.4), p = .014] or pulmonary comorbidities [RR 3.6 (95% CI 1.1, 11.6); p = .029] were independent predictors for ICU admission. Cardiac comorbidity [RR 2.6 (95% CI: 1.1, 6.5), p = .038] was an independent predictor of mortality whereas MM/AL in remission was associated with lower mortality [RR 0.4 (95% CI: 0.2–0.8); p = .008].

PURPOSE Binary cardiac response assessment using cardiac biomarkers is prognostic in light chain amyloidosis. Previous studies suggested four-level cardiac responses using N-terminal prohormone of brain natiuretic peptide improves prognostic prediction. This study was designed to validate graded cardiac response criteria using N-terminal prohormone of brain natiuretic peptide/brain natiuretic peptide. PATIENTS AND METHODS This retrospective, multicenter study included patients with light chain amyloidosis who achieved at least a hematologic partial response (PR) and were evaluable for cardiac response. Four response criteria were tested on the basis of natriuretic peptide response depth: cardiac complete response (CarCR), cardiac very good partial response (CarVGPR), cardiac PR (CarPR), and cardiac no response (CarNR). Response was classified as best response and at fixed time points (6, 12, and 24 months from therapy initiation). The study primary outcome was overall survival. RESULTS 651 patients were included. Best CarCR, CarVGPR, CarPR, and CarNR were achieved in 16%, 26.4%, 22.9%, and 34.7% of patients, respectively. Patients in cardiac stage II were more likely to achieve CarCR than patients in cardiac stage IIIA and IIIB (22% v 13.5% v 3.2%; P < .001). A deeper cardiac response was associated with a longer survival (5-year overall survival 93%, 79%, 65%, and 33% for CarCR, CarVGPR, CarPR, and CarNR, respectively; P < .001). Fixed time-point analyses and time-varying covariates Cox regression analysis, to minimize survivorship bias, affirmed the independent survival advantage of deeper cardiac responses. Four-level response performed better than two-level response as early as 12 months from therapy initiation. CONCLUSION Graded cardiac response criteria allow better assessment of cardiac improvement compared with the traditional binary response system. The study re-emphasizes the importance of early diagnosis, which increases the likelihood of deep cardiac responses.

Two Letters to Blood address the risks of COVID-19 in populations with precursors of hematological disease. In the first article, Miller and colleagues report on whether clonal hematopoiesis of intermediate potential (CHIP) is associated with adverse outcomes with COVID-19, finding no association between CHIP and 28-day mortality while providing data indirectly linking IL-6 signaling and patient outcomes. In the second article, Ho and colleagues investigate the outcomes of patients with monoclonal gammopathy of undetermined significance (MGUS) with COVID-19, reporting that one-fourth had a severe infection and that on multivariable analysis, adverse outcomes are more likely if immunoparesis is present.

Abstract The treatment landscape for relapsed multiple myeloma (MM) has increased. In this study we aimed to characterize 2nd (n = 1439) and 3rd (n = 1104) line regimens and compare the results between subgroups based on the year of treatment initiation (2nd line: 2003–2008, 2009–2015, 2016–2021; 3rd line: 2004–2009, 2010–2015, and 2016–2021). In both 2nd and 3rd line we observed increasing use of novel agents (from 78–95% and from 77–95%, respectively) and triplet regimens (from 15–69% and from 21–71%, respectively). Most frequently used regimens in the last studied periods included lenalidomide-dexamethasone (RD; 14%), carfilzomib-RD (12%) and daratumumab-RD (10%) for 2nd line, and daratumumab-pomalidomide-dexamethasone (11%) and daratumumab-RD (10%) for 3rd line. Median time to next treatment from 2nd line therapy has improved from 10.4 months (95% CI 8.4–12.4) to 16.6 months (95% CI 13.3–20.3; p < 0.001). The median overall survival from 1st relapse increased from 30.9 months (95% CI 26.8–183.0) to 65.8 months (95% CI 50.7–72.8; p < 0.001). Over the last two decades more patients were treated with newer agents and triplets for relapsed MM. The landscape of regimens has become more diverse, and the survival after 1st relapse is continually improving.