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Background: Treatments for multiple myeloma (MM) have evolved over time and improved MM survival. While racial differences in MM treatment and prognosis between non‐Hispanic African American (NHAA) and non‐Hispanic White (NHW) patients are well‐established, it is unclear whether they have persisted after the introduction of novel agents. Methods: Using the Surveillance, Epidemiology, and End Results‐Medicare linked database, our study investigated racial difference in the receipt of treatment within 1 year following diagnosis and assessed survival outcomes among Medicare beneficiaries (≥66 years) diagnosed with MM from 2007 to 2017. We applied multivariable Cox proportional hazards models to estimate the association between race and survival and presented hazard ratios (HRs). Results: Of 2094 NHAA and 11,983 NHW older patients with MM, 59.5% and 64.8% received treatment during the first year, respectively. Discrepancy in the proportion of patients receiving treatment between the two groups increased from 2.9% in 2007 to 2009 to 6.9% in 2014–2017. After controlling for relevant factors, patients who received treatment within the first year had lower mortality than those who did not (HR = 0.90, 95% confidence interval [CI]: 0.86–0.94). NHAA patients had a lower probability to receive treatments during the first year than NHW patients (HR = 0.91, 95% CI: 0.85–0.97) but had lower mortality (HR = 0.94, 95% CI: 0.88–1.00). The lower mortality was only observed among patients who received no treatment (HR = 0.84, 95% CI: 0.77–0.93); NHAA and NHW patients who received treatment had similar survival (p = 0.63). Conclusions: The increasing racial disparity in treatment utilization over time is concerning. Efforts are needed to eliminate the barriers of receiving treatment. [ABSTRACT FROM AUTHOR]

Warm autoimmune hemolytic anemia (AIHA) is a hematologic disorder with an incidence of 1–3 per 105 individuals/year. Patients with systemic lupus erythematosus (SLE) develop AIHA in 3% of adult cases and 14% of pediatric cases. We report a case of AIHA refractory to multiple lines of treatment in a patient with SLE, who eventually responded to a proteasome inhibitor‐based combination. A patient with systemic lupus erythematous was diagnosed with symptomatic autoimmune hemolytic anemia. The patient was refractory to multiple lines of treatment including prednisone, intravenous immune globulin, methylprednisolone, rituximab, cyclophosphamide, mycophenolate mofetil, and splenectomy. She eventually had a beneficial response to a proteasome inhibitor‐based combination with bortezomib plus mycophenolate mofetil. The treatment of refractory autoimmune hemolytic anemia can be challenging. Patients with AIHA refractory to primary or secondary treatments must resort to receiving novel therapeutic modalities including combinations targeting plasma cell, T‐ and B‐cell proliferation. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Asymptomatic hyperbilirubinemia in a patient with no underlying liver disease or renal impairment while on lenalidomide therapy may be attributable to the unmasking of previously undiagnosed Gilbert's syndrome, as previously shown in the literature. The hyperbilirubinemia should resolve after discontinuation of the drug. [ABSTRACT FROM AUTHOR]

Natural killer T (iNKT) cells can help mediate immune surveillance against tumors in mice. Prior studies targeting human iNKT cells were limited to therapy of advanced cancer and led to only modest activation of innate immunity. Clinical myeloma is preceded by an asymptomatic precursor phase. Lenalidomide was shown to mediate antigen-specific costimulation of human iNKT cells. We treated 6 patients with asymptomatic myeloma with 3 cycles of combination of ct-galactosylceramide-loaded monocyte-derived dendritic cells and low-dose lenalidomide. Therapy was well tolerated and led to reduction in tumor-associated monoclonal immunoglobulin in 3 of 4 patients with measurable disease. Combination therapy led to activation-induced decline in measurable iNKT cells and activation of NK cells with an increase in NKG2D and CD56 expression. Treatment also led to activation of monocytes with an increase in CD16 expression. Each cycle of therapy was associated with induction of eosinophilia as well as an increase In serum soluble IL2 receptor. Clinical responses correlated with pre-existing or treatment-induced antitumor T-cell immunity. These data demonstrate synergistic activation of several innate immune cells by this combination and the capacity to mediate tumor regression. Combination therapies targeting iNKT cells may be of benefit toward prevention of cancer in humans. [ABSTRACT FROM AUTHOR]

Natural killer T (NKT) cells are a distinct subset of T cells that recognize lipid antigens in the context of CD1d molecules. There is a considerable body of evidence implicating a role for NKT cells in regulating antitumor immunity in mice. α-Galactosylceramide (α-GalCer) is a potent agonist ligand for type I NKT cells. We and others have shown that injection of α-GalCer-loaded dendritic cells leads to clear expansion of NKT cells in vivo in cancer patients. Preclinical studies suggest the capacity of thalidomide analogues to enhance ligand-dependent NKT activation and provide the rationale for combination approaches that are now being designed. Recently, we demonstrated the presence of CD1d-restricted T cells specific for an inflammation-associated lipid, lysophosphatidylcholine, in patients with advanced myeloma. These studies suggest that type II NKT cells may play a role in sensing and regulating inflammation. Harnessing CD1d-restricted T cells in cancer may depend on regulating the balance between type I and II NKT cells and holds promise as a broad strategy for immune therapy of several cancers. [ABSTRACT FROM AUTHOR]

Background: Polycythemia vera (PV) and essential thrombocythemia (ET) are linked to increased risk of cardiovascular morbidity and mortality. In addition to the reduction in of arterial thrombotic events, statins may prevent venous thrombosis including among patients with cancer. As previous registry‐ and claims‐based studies revealed that the use of statins may improve the survival of patients with various malignancies we evaluated their impact on outcomes of older adults with PV and ET. Methods: We identified 4010 older adults (aged 66–99 years at diagnosis) with PV (n = 1809) and ET (n = 2201) in a population‐based cohort study using the Surveillance, Epidemiology, and End Results‐Medicare database with median follow‐up of 3.92 (interquartile range: 2.58–5.75) years. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were utilized to assess potential association between statins and overall survival. Multivariable competing risk models with death as a competing risk were used to evaluate possible relationship between statins and the incidence of thrombosis. Results: 55.8% of the patients used statins within the first year after PV/ET diagnosis, and statin use was associated with a 22% reduction in all‐cause mortality (PSM: hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63–0.98, p = 0.03; IPTW: HR = 0.79, 95% CI: 0.64–0.97, p = 0.03). Statins also reduced the risk of thrombosis in this patient population (PSM: HR = 0.63, 95% CI: 0.51–0.78, p < 0.01; IPTW: HR = 0.57, 95% CI: 0.49–0.66, p < 0.01) as well as in PV and ET subgroups. Conclusions: These findings suggest that it may be important to incorporate statins into the therapeutic strategy for older adults with PV and ET. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine risk factors for iv iron infusion‐related reactions (IRR), and identify strategies for iron repletion after IRR. Methods: We conducted a retrospective chart review of patients treated in the classical hematology clinic at Yale Cancer Center (n = 330 consecutive patients) from 2016 to 2021, who received iv ferumoxytol (60.3%), iron sucrose (14.8%), or iron dextran (10.9%). Results: The iv iron IRR was noted in 58 (17.6%) patients, 62.1% of whom had previously tolerated iv iron. The severity of IRR was mild in 22, moderate in 23, and severe in 11 patients. Most (72.4%) patients who experienced IRR tolerated a subsequent iv iron infusion. On multivariable analysis, a history of non‐medication allergies was associated with greater odds of IRR (odds ratio [OR] 2.12, 95% confidence interval (CI): 1.16–3.87, p =.01). No patients with type AB blood, and few with type A blood (n = 6), had IRR; compared to type A or AB together, patients with type B (OR 5.00, 95% CI: 1.56–16.06, p =.007) or type O (OR 3.71, 95% CI: 1.44–9.55, p =.007) blood had greater odds of IRR. Conclusions: This study highlights a possible association of blood type with iv iron IRR; prospective studies with larger patient numbers are warranted to explore this association. [ABSTRACT FROM AUTHOR]

Background The COVID-19 pandemic has led to delays in patients seeking care for life-threatening conditions; however, its impact on treatment patterns for patients with metastatic cancer is unknown. We assessed the COVID-19 pandemic's impact on time to treatment initiation (TTI) and treatment selection for patients newly diagnosed with metastatic solid cancer. Methods We used an electronic health record–derived longitudinal database curated via technology-enabled abstraction to identify 14 136 US patients newly diagnosed with de novo or recurrent metastatic solid cancer between January 1 and July 31 in 2019 or 2020. Patients received care at approximately 280 predominantly community-based oncology practices. Controlled interrupted time series analyses assessed the impact of the COVID-19 pandemic period (April-July 2020) on TTI, defined as the number of days from metastatic diagnosis to receipt of first-line systemic therapy, and use of myelosuppressive therapy. Results The adjusted probability of treatment within 30 days of diagnosis was similar across periods (January-March 2019 = 41.7%, 95% confidence interval [CI] = 32.2% to 51.1%; April-July 2019 = 42.6%, 95% CI = 32.4% to 52.7%; January-March 2020 = 44.5%, 95% CI = 30.4% to 58.6%; April-July 2020 = 46.8%, 95% CI= 34.6% to 59.0%; adjusted percentage-point difference-in-differences = 1.4%, 95% CI = −2.7% to 5.5%). Among 5962 patients who received first-line systemic therapy, there was no association between the pandemic period and use of myelosuppressive therapy (adjusted percentage-point difference-in-differences = 1.6%, 95% CI = −2.6% to 5.8%). There was no meaningful effect modification by cancer type, race, or age. Conclusions Despite known pandemic-related delays in surveillance and diagnosis, the COVID-19 pandemic did not affect TTI or treatment selection for patients with metastatic solid cancers. [ABSTRACT FROM AUTHOR]

Background: With improving survival for patients with multiple myeloma (MM), supportive care that is focused on optimizing quality of life and minimizing treatment-related toxicities is increasingly important. The extent to which patients with MM are receiving recommended supportive care is unknown.Methods: This study used the Surveillance, Epidemiology, and End Results-Medicare database to identify older adults (age ≥66 years) diagnosed with MM in 2008-2013 who had received active treatment and survived 1 year or longer after their diagnosis. Outcomes of interest included guideline-recommended supportive care, which was defined as 1) bone-modifying drugs (BMDs) within the 12 months after the diagnosis, 2) influenza vaccination in the first season after the diagnosis, and 3) concomitant use of prophylactic antivirals with proteasome inhibitors. Multivariable logistic regression models were used to evaluate associations between patient/facility-level characteristics and supportive care use.Results: Among 1996 patients receiving MM-directed therapy, 64%, 52%, and 49% received BMDs, an influenza vaccination, and antiviral prophylaxis, respectively. Non-Hispanic black patients (odds ratio [OR] vs white patients, 0.63; 95% confidence interval [CI], 0.46-0.88) and patients with baseline renal impairment (OR, 0.43; 95% CI, 0.34-0.54) had lower odds of BMDs. Non-Hispanic blacks (OR, 0.52; 95% CI, 0.37-0.73) and those with dual Medicaid enrollment (OR, 0.76; 95% CI, 0.58-0.99) had lower odds of influenza vaccination. Treatment in a community-based setting was associated with reduced odds of antiviral prophylaxis (OR, 0.58; 95% CI, 0.46-0.72).Conclusions: Substantial underutilization of guideline-recommended supportive care was observed among older adults with MM in the United States, and this was associated with both patient and facility characteristics. Targeted interventions are needed to improve supportive care for patients with MM. [ABSTRACT FROM AUTHOR]

CD14 and the toll-like receptor 4 have been known to play an important role in lipopolysaccharide-induced cellular responses in bacterial infections. Although CD14 and toll-like receptor 4 expression has been demonstrated in a number of myeloid cells, much less is known about the expression and function of these lipopolysaccharide receptors on nonleukocytes. In this study, we demonstrate that human keratinocytes are capable of expressing functional CD14 and toll-like receptor 4. Keratinocytes were found to constitutively express CD14 and toll-like receptor 4 mRNA that was augmented by exposure to lipopolysaccharide. Cell surface expression of keratinocyte CD14 and toll-like receptor 4 was detected by flow cytometry. Lipopolysaccharide binding to keratinocyte CD14 and toll-like receptor 4 resulted in a rapid intracellular Ca2+ response, nuclear factor-κB nuclear translocation, and the secretion of proinflammatory cytokines and chemokines. These results have important implications for our understanding of cutaneous innate immunity to bacterial infections of the skin. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the accuracy of the analysis of blood and bone marrow samples using electronic medical records.