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Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti–SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered. The nonmechanically ventilated patients (n = 36) had an intubation rate of 13.9% and a 30-day survival rate of 88.9%, and the overall survival rate for a comparative group based on network data was 72.5% (1625/2241). Patients had negative nasopharyngeal swab rates of 43.8% and 73.0% on days 10 and 30, respectively. Patients mechanically ventilated had a day-30 mortality rate of 46.7%; the mortality rate for a comparative group based on network data was 71.0% (369/520). All evaluable patients were found to have neutralizing Abs on day 3 (n = 47), and all but 1 patient had Abs on days 30 and 60. The only adverse event was a mild rash. In this study on patients with COVID-19 disease, we show therapeutic use of CCP was safe and conferred transfer of Abs, while preserving endogenous immune response., Patients with COVID-19 pneumonia receiving high-titer convalescent plasma showed antibody transfer with preservation of endogenous production, and database survival comparison is promising for the early group.

OBJECTIVESTo determine the rate of intubation, overall survival, viral clearance, and the development of endogenous antibodies in patients with COVID-19 pneumonia treated with convalescent plasma containing high levels of neutralizing anti-SARS-CoV-2 antibodies. We also aimed to describe the laboratory parameters of the plasma products.DESIGNThis was a phase IIa, single institution, prospective study in adults hospitalized with SARS-CoV-2 pneumonia.SETTINGHackensack University Medical Center, a 770-bed research and teaching hospital located in Bergen County NJ, 11 km from New York City. The study was conducted between April 15 and June 18, 2020.PARTICIPANTS47 hospitalized adult patients were treated: 32 in the non-mechanically ventilated group and 15 in the mechanically ventilated group. All patients had confirmed SARS-CoV-2 pneumonia by radiographic and laboratory evaluation.INTERVENTIONFresh or frozen convalescent plasma from donors with high titers of viral neutralizing antibodies was administered.MAIN OUTCOME MEASURESIncidence of intubation, overall survival, and discharge rate of patients divided in cohorts based on severity of disease. Description of infused plasma characteristics. Evaluation of recipients’ pre-treatment viral immunity, immunity transfer from convalescent plasma administration, and late immunity 30 and 60 days after treatment. Rates of viral clearance by nasopharyngeal PCR at 10 and 30 days. Outcomes of patients with no pre-treatment immunity. Survival comparison with institutional data for each cohort.RESULTSAnalysis for the non-mechanically ventilated patients showed an intubation rate of 15.6% (95% CI: 5.3%-32.8%) and a day-30 survival rate of 87.5% (28/32; 95% CI:70.2%-96.4%). The overall survival for a comparative group based on institutional data was 66% (675/1023; p=0.012). The rates of negative nasopharyngeal swab by PR-PCR on day+10 and +30 post treatment were 42.9% (95% CI: 24%-63%) and 78% (95% CI: 56%-93%) respectively. Patients mechanically ventilated had a day-30 mortality of 46.7% (95% CI:21.3%-73.4%); the mortality for a comparative group based on institutional data was 68.5% (217/317; p=0.093). The rates of negative nasopharyngeal swab by PR-PCR at day+10 and +30 was 85.7% (95% CI: 42-100%; n=7) and 100% (95% CI: 63-100%; n=8). Seven patients (15%) had no pre-infusion immunity, and all were found to have anti-SARS-CoV-2 neutralizing titers three days post infusion. All evaluable patients were found to have neutralizing antibodies on day+30 (n=30) and on day+60 (n=12) post treatment. There was no difference in outcomes within the ranges of high antiviral neutralizing titers used, mostly greater than 1:1000. There was also no difference between fresh or frozen plasma. The only adverse event was a mild rash in one patient.CONCLUSIONIn this study of adult patients hospitalized with SARS-CoV-2 pneumonia, convalescent plasma was safe and conferred effective transfer of immunity while preserving endogenous immune response. Intubation rates, survival rates compared with institutional data, and viral clearance rates, support the continued evaluation of this antiviral modality.STUDY REGISTRATIONClinicalTrials.gov NTC04343755

8027Background: Escalating doses of Vel with high dose Mel (Rowley, ASH 2009) and escalating doses of Thal with Vel + Mel (Hong, ASH 2012) as ASCT conditioning in pts with advanced MM were previous...

Abstract 3104 Thalidomide is an active agent in the treatment of MM and shows additive and/or synergistic effects when combined with various chemotherapeutics in pre-clinical and clinical models. We conducted a phase I/II study of Thal in combination with Vel and high dose Mel with PBSCT in patients (pts) with either disease progression or less than complete response after a prior PBSCT. Inclusion criteria included a diagnosis of MM and the availability of adequate PBSC. Exclusion criteria were dose-intense therapy within 56 days, uncontrolled infections, uncontrolled CNS metastases, known cardiac amyloid deposition, severe organ dysfunction, Karnofsky score 500/uL 10 days (range, 8–14 days), ANC >1000/uL 10 days (range 9–14 days), and plt >20,000 12 days (range 9–25 days). 28 pts (median age, 56) were enrolled in the phase I and phase II portions of the study. 18 pts were treated for disease progression after prior autologous transplant (median lines of prior therapy =2; range, 1–5); only 22% of pts achieved ≥PR to the most recent therapy prior to PBSCT. 7 pts were enrolled after achieving Our results indicate that high-dose Thal can be safely added up to 1000 mg daily for 5 days to dose-intense Mel and Vel with acceptable toxicities. Confirmation of potential synergistic effects of this combination regimen will require an appropriately designed phase III study. Disclosures: Siegel: Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vesole:Celgene Corp.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.