Faculty Bibliography

Background: Tremendous therapeutic progress has been made over the past decade in the field of multiple myeloma (MM). Although the incidence of MM is twice as high for black compared to white individuals, mortality rates remain higher for black patients (Marinac, et al. Blood Ca J 2020). In addition, black Americans are significantly less likely to participate in clinical trials in general (Hong, et al. Am J Prev Med 2021), leading to disproportionate enrollment in studies of novel agents. Various factors may account for these disparities, including access to clinical trials, clinician bias, and hesitancy to enroll in clinical trials among different patient populations. Furthermore, underrepresentation of racial groups within clinical trials impacts the generalizability of important findings from these studies. Here we characterized the racial representation of MM clinical trials.
Method(s): Randomized clinical trials focused on MM interventions published between 2012-2022 were included. We screened 431 publications during this period and characterized racial demographics as available in the literature. A twosided Cochran-Armitage Trend Test was used to assess if there was a linear trend in the percentage of black participants in clinical trials over time.
Result(s): Among 431 studies published over the past 10 years, 76 collected over past 5 years that included racial demographic details were included. Among the 38,830 participants, 87.5% were white, 4.8% were black, and 7.7% were other (reported as either Asian, mixed, or other). There was a significant trend toward increased enrollment comparing over time between 2018 to 2021 (2.1 to 7.0%, p < 0.001 for trend), however black individual remained largely underrepresented in all these studies.
Conclusion(s): While the number of black participating in randomized controlled trials involving MM patients over the past five years is significantly increasing, these studies included a disproportionate number of white participants, despite the incidence of MM being higher for black patients. Efforts are underway in the field to enhance enrollment of underrepresented populations, including a recent randomized study that included 19% black MM patients (Richardson, et al. New Eng J Med 2022). Our study was limited due to many trials not reporting details about racial demographics until relatively recently. Further investigations required to examine the reasons underlying racial disparities in MM trial recruitment and enrollment

INTRODUCTION/UNASSIGNED:: Survival in multiple myeloma (MM) has improved due to the ongoing revolution of therapeutic approaches. Nevertheless, many patients relapse, and additional novel approaches are required to prolong remissions and prevent disease progression. AREAS COVERED/UNASSIGNED:Considering the success of monoclonal antibodies (mAbs) against CD38 and SLAMF7 in relapsed/refractory MM (R/R MM), additional antigens expressed on malignant plasma cells are being investigated as treatment targets. Among these, many trials are focusing on B cell maturation antigen (BCMA), using either antibody-drug conjugates (ADCs), bispecific T cell engagers (TCE), or chimeric antigen receptor T cells (CAR-T). Other potential targets include the myeloma markers CD138, GPRC5D, FcRH5, the plasma cell differentiating factors APRIL, TACI and BAFF, and the immune checkpoint proteins CD47 and TIGIT. Additionally, novel immunomodulatory Cereblon E3 Ligase Modulators (CELMoDs) offer the potential to overcome resistance to conventional immunomodulatory agents. Based upon PubMed and abstract searches primarily from the past 4 years, here we review the data supporting novel immunotherapies for R/R MM. EXPERT OPINION/UNASSIGNED:: Overcoming disease resistance remains a challenge in R/R MM. Novel therapeutic approaches targeting MM antigens and/or enhancing immune cell function offer the potential to prolong survival and are actively being investigated in clinical trials.

Background: Numerous predictors of poor outcome in COVID-19 patients have been identified, including alterations in the composition of leukocytes in the peripheral blood. There nonetheless remains a need to improve predictions of patient outcomes following hospitalization in order to appropriately triage patients. We addressed this question by evaluating hematologic parameters and peripheral blood smear morphology in patients who either died or recovered following hospitalization.
Design(s): The study groups included 48 patients who died following admission ("cases") and 48 age-matched controls who recovered ("controls"). Laboratory values were collected for PCR-positive COVID-19 hospitalized patients at two time points: T1- the time of admission, and T2 - the time of discharge/death. Peripheral blood smears from two-time points for patients who died were analyzed independently by 4 pathologists.
Result(s): Study patient demographic details are shown in Table 1. Anemia and thrombocytopenia were present at the time of admission in both groups, and there was a significant decline in hemoglobin and RBC count between T1 and T2; PLT counts decreased, but not in a statistically significant manner (Table 2). WBC and absolute neutrophils increased following admission specifically in patients who died of disease (Table 2). No statistically significant differences were observed in all other hematologic parameters evaluated. Blood from patients who died showed pseudo Pelger-Huet changes 60.41% (n=29), toxic granulations 8.3% (n=4), atypical lymphocytes 91% (n=44), and giant platelets 94% (n=45) with immature myeloid forms increasing at T2. In contrast to patients who recovered , patients who died showed increased D-dimer values at admission; D-dimer values did not correlate with the presence of thrombocytopenia.
Conclusion(s): Hospitalized COVID-19 patients who died showed: 1) elevated D-dimer levels at admission; and 2) increasing WBC and neutrophil counts during their hospitalization. While several morphologic changes were observed in the blood in those who subsequently died, the changes observed were not specific to COVID-19; however, the presence of immature myeloid precursors in hospitalized patients was associated with subsequent neutrophilia and death. This finding suggests that in addition to closely monitoring the two laboratory parameters describe above, special care should be taken to asses blood films for the presence of immature myeloid precursors. Additional studies will be required to validate these findings in a larger group of hospitalized patients (Figure Presented)