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Background Newly diagnosed multiple myeloma patients have many available treatment options. While lenalidomide, bortezomib, and dexamethasone (RVD) is the preferred initial treatment for many patients, several other agents may provide similar efficacy with less toxicity and improved ease of administration. Methods We evaluated the safety and efficacy of the all-oral regimen of ixazomib, cyclophosphamide, and dexamethasone with the use of metronomic cyclophosphamide dosing in the treatment of patients with newly diagnosed multiple myeloma. Results The study was stopped prior to planned enrollment due to slow recruitment, with 12 patients available for final analysis. The overall response rate was 58.3% with 2 patients achieving a very good partial response (16.7%) and 5 patients achieving a partial response (41.7%). Median progression-free survival was 16 months, and median overall survival was 43 months. There were no episodes of grade 3 or greater peripheral neuropathy. Grade 3 or greater dermatologic toxicity was experienced in 50% of patients. Conclusion Although limited enrollment prevented full efficacy evaluation, our data do not support further study of metronomic cyclophosphamide in combination with ixazomib and dexamethasone in the treatment of newly diagnosed multiple myeloma. The activity of this regimen in the relapsed/refractory setting requires further study (ClinicalTrials.gov Identifier: NCT02412228).

Background The frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection. Methods We included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality. Results Among 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age >50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33–1.95) and fungal (OR, 2.20; 95% CI, 1.28–3.76) coinfections. Conclusions Viral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes.

Introduction. Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM) is a rare lymphoma affecting older patients. Its management largely relies on small phase II trials and it is unclear how their results translate into clinical practice in the community. Method. We evaluated changes in the presentation, management, and survival among 2,666 Medicare beneficiaries diagnosed with WM between 1994 and 2011, using Medicare claims linked to Surveillance, Epidemiology and End Results data. Results. Prevalence of transfusions, anemia, thrombocytopenia, and neuropathy at diagnosis significantly increased over time, whereas the use of plasmapheresis was low (2.5%) and stable. The proportion of patients starting chemotherapy within 1 year of WM diagnosis increased from 39% in 1994 to 62% in 2011 (p < .0001). Treatments based on classic alkylators and purine analogs predominated in the 1990s, but were quickly replaced by rituximab-containing regimens after 2000. Rituximab monotherapy has been prescribed for >50% of patients since 2004, and combination chemoimmunotherapy for a further 30%. Most patients initiating multiagent regimens in 2012–2013 received rituximab with bortezomib or bendamustine. These changes were accompanied by significant improvements in overall and WM-related survival, but also by a significant increase in cost of chemotherapy. Mean Medicare payments for chemotherapy drugs accrued in the first year of treatment rose from $9,464 in 1994–2000 to $29,490 after 2008. Conclusion. Hematologists have rapidly adopted innovative, expensive therapies for WM before completion of randomized trials. This underscores the need to assess the comparative value of such therapies in rare malignancies through a combination of clinical and observational data.

Pulte et al. [1] described significant insurance-related disparities among younger patients with non-Hodgkin lymphoma (NHL), with hazard ratios for overall survival of 1.92 and 2.51 in the uninsured or Medicaid populations, respectively. Their findings complement recently identified disparities in diffuse large B-cell lymphoma (DLBCL) survival by socioeconomic status, particularly pronounced among patients less than 65 years old [2]. However, the Surveillance, Epidemiology and End Results data set used by Pulte et al. lacks important confounders of survival in NHL: performance/comorbidity status, human immunodeficiency virus (HIV) status, the International Prognostic Index (IPI) [3], and chemotherapy use. We further explored those insurance-related disparities using the National Cancer Data Base (NCDB), a joint project of the American Cancer Society and the Commission on Cancer of the American College of Surgeons, which captures more than 70% of incident cancer cases in the United States. Advantageously, the NCDB contains data on the Charlson-Deyo comorbidity index [4], HIV status, chemotherapy administration and the IPI in a subset (11%) of all reported DLBCL cases. Among 5,797 patients aged 18–64 years diagnosed with DLBCL between 2004 and 2011, those confounders had a significantly different prevalence among groups with various types of health insurance (Table 1). In particular, nearly a quarter of those younger Medicaid patients were HIV-positive, and more than 40% had high-intermediate or high IPI, compared with only 27% of patients with private insurance. Additionally, Medicaid and Medicare beneficiaries had higher rates of comorbidities. This is explained by eligibility criteria for those state-sponsored programs, which are tied to medical disability in the younger age groups. Table 1. Confounders of survival in diffuse large B-cell lymphoma among patients aged 18–64 years with different types of health coverage In multivariable Cox models adjusting for age, sex, race, comorbidity index, and stratified by the IPI, HIV status, and stage (which violated the proportional hazard assumption), the adjusted hazard ratios for overall survival were: 1.26 for the uninsured (95% confidence interval [CI], 1.05–1.52), 1.52 for Medicaid (95% CI, 1.31–1.76), and 1.47 for Medicare (95% CI, 1.26–1.71). These estimates, although still significant, were notably lower than those calculated by Pulte et al., indicating that the insurance-associated disparities are partly mediated by prevalence of known prognostic factors in DLBCL or by patients’ pre-existing medical conditions that determine eligibility for specific health insurance. The relative risk of nonreceipt of chemotherapy (adjusted for the same confounders) in a robust Poisson model was 1.58 (95 CI, 1.15–2.18) for the uninsured, 1.60 (95% CI, 1.23–2.09) for Medicaid, and 1.65 (95% CI, 1.24–2.19) for Medicare, demonstrating direct disparity in the delivery of standard curative treatment. Cancer registries constitute a popular data source for the study of disparities, but they offer limited insight into their cause. Our results highlight that to quantify and interpret such disparities, confounders related to patients’ baseline status or disease biology have to be separated from socioeconomic factors affecting health care quality that could respond to policy or system interventions [5, 6]. Another layer of complexity may arise from differences in histologic or molecular characteristics. Those remain largely unexplored, although they may also confound racial or socioeconomic disparities, as recently shown in some hematologic malignancies [7, 8].