IMPORTANCEThe benefit of high-dose dexamethasone and oxygenation strategies vs standard of care for patients with severe acute hypoxemic respiratory failure (AHRF) caused by COVID-19 pneumonia is debated.OBJECTIVES To assess the benefit of high-dose dexamethasone compared with standard of care dexamethasone, and to assess the benefit of high-flow nasal oxygen (HFNO 2 ) or continuous positive airway pressure (CPAP) compared with oxygen support standard of care (O 2 SC). DESIGN, SETTING, AND PARTICIPANTSThis multicenter, placebo-controlled randomized clinical trial was conducted in 19 intensive care units (ICUs) in France from April 2020 to January 2021. Eligible patients were consecutive ICU-admitted adults with COVID-19 AHRF. Randomization used a 2 × 3 factorial design for dexamethasone and oxygenation strategies; patients not eligible for at least 1 oxygenation strategy and/or already receiving invasive mechanical ventilation (IMV) were only randomized for dexamethasone. All patients were followed-up for 60 days. Data were analyzed from May 26 to July 31, 2021.INTERVENTIONS Patients received standard dexamethasone (dexamethasone-phosphate 6 mg/d for 10 days [or placebo prior to RECOVERY trial results communication]) or high-dose dexamethasone (dexamethasone-phosphate 20 mg/d on days 1-5 then 10 mg/d on days 6-10). Those not requiring IMV were additionally randomized to O 2 SC, CPAP, or HFNO 2 . MAIN OUTCOMES AND MEASURESThe main outcomes were time to all-cause mortality, assessed at day 60, for the dexamethasone interventions, and time to IMV requirement, assessed at day 28, for the oxygenation interventions. Differences between intervention groups were calculated using proportional Cox models and expressed as hazard ratios (HRs). RESULTS Among 841 screened patients, 546 patients (median [IQR] age, years; 414 [75.8%] men) were randomized between standard dexamethasone (276 patients, including 37 patients who received placebo) or high-dose dexamethasone (270 patients). Of these, 333 patients were randomized among O 2 SC (109 patients, including 56 receiving standard dexamethasone), CPAP (109 patients, including 57 receiving standard dexamethasone), and HFNO 2 (115 patients, including 56 receiving standard dexamethasone). There was no difference in 60-day mortality between standard and high-dose dexamethasone groups (HR, 0.96 [95% CI, 0.69-1.33]; P = .79). There was no significant difference for the cumulative incidence of IMV criteria at day 28 among O 2 support groups (O 2 SC vs CPAP: HR, 1.08 [95% CI, 0.71-1.63]; O 2 SC vs HFNO 2 : HR, 1.04 [95% CI, 0.69-1.55]) or 60-day mortality (O 2 SC vs CPAP: HR, 0.97 [95% CI, 0.58-1.61; O 2 SC vs HFNO 2 : HR, 0.89 [95% CI,). Interactions between interventions were not significant. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial among ICU patients with COVID-19-related AHRF, high-dose dexamethasone did not significantly improve 60-day survival. The oxygenation strategies in patients who were not initially receiving IMV did not significantly modify 28-day risk of...

Patients aged 80 or over with diffuse large B cell lymphoma (DLBCL) often have comorbidities that increase drug toxicity and prevent the use of otherwise optimal treatment. We performed a retrospective analysis of 43 patients aged 80 or over (median age: 83; range: 80-93) unable to receive treatment with anthracyclines, at diagnosis of DLBCL, treated with an R-CVP treatment (standard R-CHOP without doxorubicin). The patients had one or more comorbidities: 18 patients (41.9 %) had a performance status (PS) of 3; 23 patients (53.5 %) had low creatinine clearance; 12 patients (27.9 %) had low left ventricular ejection fraction; seven patients (16.3 %) had poor hepatic function; and 26 patients (60.5 %) had a Charlson index score ≥4. Thirty patients (70 %) had two or three adverse factors according to the age-adjusted International Prognostic Index. Twenty-five patients (58.1 %) received eight cycles of R-CVP, but the full eight cycles could not be given to 18 patients (41.9 %). The OR rate was 58.1 % (CR 37.2 %). There were 34 deaths (79 %) during treatment and follow-up. Ten patients (23.3 %) died early from toxicity before interim evaluation; all had PS 3. The median follow-up of surviving patients was 52.6 months. The overall 2-year survival rate was 31.9 % and the median OS was 12.6 months. The median OS for patients who completed the entire treatment was 26.4 months. The median PFS was 11.2 months. In multivariate analyses, OS was only affected by performance status ≥2 and Charlson index score ≥4. The R-CVP regimen can be active in elderly frail patients aged 80 or more with DLBCL, but systematic geriatric assessment is required so that those unsuitable for chemotherapy are excluded.

Primary nodal marginal zone lymphoma (NMZL) is a rare disease. There is no current consensus on how to treat it. The bendamustine plus rituximab (BR) regimen is effective for the treatment of follicular and other indolent lymphomas, but its efficacy in NMZL is not known. We analyzed the outcome of 14 patients diagnosed with NMZL (median age 67 years) who were treated with 375 mg/m of rituximab on day 1 and 90 mg/m of bendamustine on days 1 and 2. The overall and complete response rates were 93% and 71%, respectively. Major toxicity (grade 3/4 neutropenia) occurred in 5% of treatment courses. After a median follow-up of 22 months (range: 18-55), the overall survival and the free survival rates were 100% and 93%, respectively. None of the patients showing a complete or partial response developed secondary myelodysplastic syndrome/acute myeloid leukemia. Bendamustine plus rituximab was found to be an active and well-tolerated regimen leading to the rapid control of disease.

We performed a retrospective analysis of 93 myelodysplastic syndromes (MDS) patients with intermediate 2 or high‐risk IPSS score to study the impact of Azacitidine (AZA) relative dose intensity (RDI) <80% on the overall survival (OS). There were 51.6% of patients who had full dose and 48.4% had dose reduction or delayed with a RDI <80%. Nineteen patients (20.4%) had RDI <80% before getting objective response. Overall and progression‐free survivals (OS, PFS) probabilities for the whole population were 58% (95% CI: 48‐69) and 47% (95% CI: 38‐58) at 1 year; 35% (95% CI: 26‐47) and 31% (95% CI: 23‐43) at two years, respectively. When analyzing the outcomes according to the response to AZA, median OS was 32 months (range: 26‐55) for responders and 8 months (range: 7‐12) for nonresponders, with a respective 1‐year and 2‐year OS probabilities of 91% vs 28% and 66% vs 6%, respectively ( P < 0.001). Interestingly, there was no impact of dose reduction on OS nor on PFS, however, when analyzing the timing of dose reduction as time‐dependent variable, we found that patients who had dose reduction before achieving the objective response, had significantly lower OS ( P = 0.02) and PFS ( P = 0.01) compared to patients who had dose reduction after achieving the objective response. In multivariate analysis, acute myeloid leukemia with 21%‐30% blasts in BM and poor and very poor karyotype significantly impacted OS, (HR = 2.09, 95% CI: 1.27‐3.44, P = 0.004, and HR = 2.73, 95% CI: 1.6‐4.6, P < 0.001 respectively), as well as PFS (HR = 1.84, 95% CI: 1.07‐3.17, P = 0.028, and HR = 3.03, 95% CI: 1.7‐5.39, P < 0.001, respectively).

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