Predictors for inpatient mortality during the first wave of the SARS-CoV-2 pandemic: A retrospective analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic overwhelmed healthcare systems, highlighting the need to better understand predictors of mortality and the impact of medical interventions. METHODS: This retrospective cohort study examined data from every patient who tested positive for COVID-19 and was admitted to White Plains Hospital between March 9, 2020, and June 3, 2020. We used binomial logistic regression to analyze data for all patients, and propensity score matching for those treated with hydroxychloroquine and convalescent plasma (CP). The primary outcome of interest was inpatient mortality. RESULTS: 1,108 admitted patients with COVID-19 were available for analysis, of which 124 (11.2%) were excluded due to incomplete data. Of the 984 patients included, 225 (22.9%) died. Risk for death decreased for each day later a patient was admitted [OR 0.970, CI 0.955 to 0.985; p < 0.001]. Elevated initial C-reactive protein (CRP) value was associated with a higher risk for death at 96 hours [OR 1.007, 1.002 to 1.012; p = 0.006]. Hydroxychloroquine and CP administration were each associated with increased mortality [OR 3.4, CI 1.614 to 7.396; p = 0.002, OR 2.8560, CI 1.361 to 6.160; p = 0.006 respectively]. CONCLUSIONS: Elevated CRP carried significant odds of early death. Hydroxychloroquine and CP were each associated with higher risk for death, although CP was without titers and was administered at a median of five days from admission. Randomized or controlled studies will better describe the impact of CP. Mortality decreased as the pandemic progressed, suggesting that institutional capacity for dynamic evaluation of process and outcome measures may benefit COVID-19 survival.

A phase II study of pomalidomide, daily oral cyclophosphamide, and dexamethasone in relapsed/refractory multiple myeloma.

Relapsed/refractory multiple myeloma patients treated with pomalidomide and dexamethasone have an overall response rate (ORR) of ∼30% and median progression-free survival (PFS) of 4-5 months. Previous studies explored addition of weekly cyclophosphamide, but we hypothesized that daily dosing allows for better synergy. We report the open-label, single-center phase II study of pomalidomide, daily cyclophosphamide and weekly dexamethasone (PCD). Thirty-three patients were evaluable for efficacy and underwent 28-day cycles of pomalidomide (4 mg/day, D1-21), cyclophosphamide (50 mg b.i.d., D1-21) and weekly dexamethasone. All were lenalidomide-refractory and 55% were refractory to lenalidomide and proteasome inhibitor. ORR was 73%; median PFS and overall survival were 13.3 months and 57.2 months respectively. Grade 3/4 toxicities were primarily hematologic but manageable with dose reductions. Early disease progression correlated with MYC expression and flow cytometry demonstrates an activated microenvironment post-PCD. Addition of metronomic cyclophosphamide to pomalidomide and dexamethasone is a cost-effective, oral regimen with encouraging PFS.

A phase 2 study of panobinostat with lenalidomide and weekly dexamethasone in myeloma.

Phase 3 studies combining histone deacetylase inhibitors with bortezomib were hampered by gastrointestinal (GI) intolerance, which was not observed when combined with immunomodulatory drugs. This study is a single-center phase 2 study of panobinostat with lenalidomide and dexamethasone (FRD). Twenty-seven relapsed multiple myeloma patients were enrolled. Twenty-two patients (81%) were lenalidomide refractory and 9 (33%), 14 (52%), and 7 (26%) were refractory to pomalidomide, bortezomib, and carfilzomib, respectively. High-risk molecular findings were present in 17 (63%) patients. Responses included 2 complete responses (CRs), 4 very good partial responses (VGPRs), 5 partial responses (PRs), and 9 minimal responses (MRs) for an overall response rate of 41%, clinical benefit rate of 74%, and a disease control rate of 96%. The median progression-free survival (PFS) was 7.1 months. In the 22 lenalidomide-refractory patients, there were 1 CR, 4 VGPRs, 3 PRs, and 7 MRs, with a median PFS of 6.5 months. Median overall survival was not reached. Grade 3/4 toxicities were primarily hematologic. Gene expression profiling of enrollment tumor samples revealed a set of 1989 genes associated with short (<90 days) PFS to therapy. MAGEA1 RNA and protein expression were correlated with short PFS, and laboratory studies demonstrated a role for MAGE-A in resistance to panobinostat-induced cell death. FRD demonstrates durable responses, even in high-risk, lenalidomide-refractory patients, indicating the essential role of panobinostat in attaining responses. MAGEA1 expression may represent a functional biomarker for resistance to panobinostat. In contrast to PANORAMA 1, there were no significant GI toxicities and primarily expected hematologic toxicities. This trial was registered at www.clinicaltrials.gov as #NCT00742027.