Shah, Nishi

The bone marrow immune microenvironment (BMME) is a critical factor in multiple myeloma (MM) pathogenesis. Despite higher incidence of MM among self-identified African Americans, the relationship between African genetic similarity and the BMME remains unclear. We present the largest analysis to date assessing the impact of Ancestry on the BMME in myeloma (N=320, including 64 with ≥50% African genetic similarity, AFR-High) leveraging our recently generated Immune Atlas. AFR-High was associated with enrichment of late T-effector cells, driven by rare cytotoxic CD4⁺ T cells, suggesting a distinct adaptive BMME. AFR-High exhibited expansion of late-differentiated adaptive NK cells with high cytotoxic GNLY and GZMH expression. AFR-High depicted reduced CD14⁺ monocytes, increased CD16⁺ non-classical monocytes, and expansion of macrophage-like monocyte populations with enrichment of metabolic adaptation, efferocytosis and phagocytic clearance programs, and immunoregulatory pathways. These findings reveal a shift from an innate inflammatory immune landscape toward adaptive cytotoxic and immunoregulatory remodeling associated with African genetic similarity in MM.

Background: Recent advancements in multiple myeloma (MM) diagnosis and treatment significantly improved patients' survival and quality of life. Severe Renal Impairment (RI) remains a significant challenge in newly diagnosed MM (NDMM), complicating treatment and affecting outcomes. Prior studies reported improved overall renal recovery in the era of novel therapies. However, there is a lack of evidence documenting the outcomes of patients presenting with severe RI. We present an updated analysis of the characteristics and outcomes of patients with NDMM presenting with severe RI in an ethnically diverse, low socio-economic population. Methods: A single-center retrospective review of patients with NDMM presenting to Montefiore Medical Center (Bronx, New York) was conducted from 2011-2023. Severe RI was defined as an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m². MM risk was assessed using the mSMART 3.0 tool. Results: Out of 284 patients with NDMM, 58 (20%) patients presented with severe RI. Black patients (p = 0.018) and older adults (64 years vs 60 years, p value 0.032) were more likely to present with severe RI. Severe RI at diagnosis correlated with high-risk myeloma (p = 0.002), high R-ISS stage (p < 0.001), and a lower likelihood of receiving stem cell transplants (p < 0.001). Among those with severe RI, 23/58 required dialysis of which 6/23 were taken off dialysis at last follow-up after renal recovery. Median eGFR at diagnosis, 6 months and 1 year after diagnosis was 11, 23 and 23.5 ml/min/1.73 m2, respectively. 14 out of 58 patients (39%) achieved renal recovery to eGFR > 30 one year post-diagnosis, with no significant difference in race, sex, or ethnicity. The most common first-line treatment for patients with severe RI was CyBorD (62%). The median time from diagnosis to first treatment (including plasma exchange) was 10 days. By the last follow-up, 35/58 patients (60%) had a stem cell transplant, with a median time from diagnosis to transplant of 275 days. The median overall survival (OS) for patients with severe RI at diagnosis was 49 months, while it was not reached for those without severe RI (p < 0.001). Early death (≤ 2 months after diagnosis) occurred in 2 patients, both with severe RI. Among patients with severe RI, multivariate Cox regression survival analysis showed that achieving free light chain (FLC) below 500 mg/L (HR 0.212, p < 0.001) and receiving a stem cell transplant (HR 0.209, p 0.002) improved outcome. Conclusions: Despite improvements in the life expectancy of patients with MM, severe renal failure remains a challenge, particularly among minorities. Socioeconomic factors need to be explored as a contributor to outcomes in patients with severe RI. Achieving FLC clearance and undergoing stem cell transplant may play a role in survival in patients with NDMM and severe RI.

Patients with multiple myeloma (MM) are at a high risk for developing cardiovascular complications. Global longitudinal strain (GLS) can detect early functional impairment before structural abnormalities develop. It remains unknown if reduced GLS is associated with reduced survival in patients with MM. We conducted a retrospective cohort analysis of patients diagnosed with MM between 1 January 2000 and 31 December 2017 at our institution. Patients with a 2D transthoracic echocardiogram completed within 1 year of MM diagnosis, left ventricular ejection fraction (LVEF) greater than 40%, and no history of myocardial infarction prior to MM diagnosis were included. GLS was measured using an artificial-intelligence-powered software (EchoGo Core), with reduced GLS defined as an absolute value of <18%. The primary outcome of interest was overall survival since myeloma diagnosis. Our cohort included 242 patients with a median follow up of 4.28 years. Fifty-two (21.5%) patients had reduced average GLS. Patients with reduced GLS were more likely to have an IVSd ≥ 1.2cm, E/E’ > 9.6, LVEF/GLS > 4.1, higher LV mass index, and low-voltage ECG. A Total of 126 (52.1%) deaths occurred during follow-up. Overall survival was lower among patients with reduced GLS (adjusted HR: 1.81, CI: 1.07–3.05).

Abstract Background/Introduction Patients with multiple myeloma (MM) are at increased risk of developing AL amyloidosis. It was determined by screening fat pad and bone marrow biopsy that 38% MM patients had amyloidosis at time of diagnosis and the majority were asymptomatic (1). However, whether amyloidosis-related echo features in MM affect survival remains unknown (1, 2). Purpose The goals of our study are to: 1) characterize prevalence of amyloidosis-related echo features in patients with multiple myeloma, 2) investigate whether decrease in longitudinal strain affect survival outcomes. Methods Patients diagnosed with MM between Jan 1, 2000 and Dec 31, 2017 at our institution were identified through Clinical Looking Glass. Those with echo within 1 year after myeloma diagnosis and left ventricular ejection fraction (LVEF) greater than 40% were included. Global longitudinal strain (GLS) and LVEF measurements were done using EchoGo (Ultromics, Oxford, UK). The average of GLS obtained from apical 4-chamber and apical 2-chamber views was used for analysis, with decreased GLS defined as absolute value less than 18%. Statistical analysis was conducted with STATA13, using Chi square test and Kruskal-Wallis for univariable analysis and Cox regression model for survival analysis. Results From a total cohort of 909 patients, 252 met inclusion criteria, of which 59 (23.4%) patients had decreased average GLS (see Table 1). Patients' mean age was 63±11 years, 44.8% were male and most were Black (42.7%) and the rest Hispanic (33.3%) and White (7.9%). Median follow up time was 4.25 years. The group with decreased GLS had lower percentage of females (22% vs 51.8%, p&lt;0.01), higher percentage of previous MI (11.9% vs 1.6%, p&lt;0.01) and more prior diagnosis of heart failure (20.3% vs 1.6%, p&lt;0.01). Among patients with decreased GLS, five-year mortality rate was 63.3% compared to 46.0% in those with preserved GLS (p&lt;0.036). Median survival time was 3.9 years among those with reduced GLS and 4.3 years in those without (see Figure 1; p&lt;0.01). Reduced GLS correlated with decreased survival (HR 1.6, p=0.03) even after adjusting for demographic variables (age, gender, race), history of MI, history of CHF, Charlson comorbidity index, myeloma RISS stage, and LVEF (≥50% vs 40–50%). Forty-seven (18.6%) patients had end diastolic inter-ventricular septum (IVSd) thickness ≥1.2cm. Median GLS in patients with increased IVSd thickness was 19% compared to 21% in those without (p=0.01). Nine patients had the apical sparing strain pattern for amyloidosis. Total of 158 patients had bone marrow specimen stained with Congo-red with 7 (4.4%) testing positive. Median GLS was 19% in the group staining positive for Congo-red compared 21% in the group with negative stain (p=0.03). Conclusions Decrease in GLS on baseline echo correlates with increased mortality in patients with MM and may be due to subclinical cardiac amyloidosis. Funding Acknowledgement Type of funding sources: None.