542. Use of Bamlanivimab in Cancer Patients with Mild-to-Moderate COVID-19

Abstract Background Bamlanivimab is a monoclonal antibody that was granted an emergency use authorization by the US Food and Drug Administration in November 2020 for patients with mild to moderate coronavirus disease 2019 (COVID-19). It initially showed promising results with decreasing hospitalizations and return emergency department visits in immunocompetent patients. We evaluated the role of bamlanivimab in the cancer patient population. Methods We conducted a retrospective matched study of all cancer patients diagnosed with mild to moderate COVID-19 who received bamlanivimab in our acute cancer care center (ACCC) from December 2020 to February 2021. These patients were compared to a control group of cancer patients who presented to our ACCC and were diagnosed with mild to moderate COVID-19 from March to November 2020 before the introduction of bamlanivimab. Control patients were matched by age and underlying malignancy. All patients had a baseline oxygen saturation ≥ 94% and an absolute neutrophil count > 500 mm3. Demographics, clinical characteristics, and outcome that included COVID-related admissions, oxygen desaturation, ICU admission and 30-day mortality were compared in both groups. Results A total of 108 patients were analyzed with 54 patients in each group, of which 59% consisted of hematologic malignancies, and 33% were ≥ 65 years. The presenting symptoms were similar in both groups and mainly consisted of cough, fever, and dyspnea. Patients who received bamlanivimab were less likely to be admitted to the hospital (24% vs. 91%; p< 0.0001), experience oxygen desaturation < 94% during follow-up (11% vs 44%; p=0.0001), require oxygen supplement (7% vs. 44%; p< 0.0001), or be admitted to the ICU (4% vs 15%; p=0.046). No 30-day mortality was observed in the bamlanivimab group with 2 (4%) occurring in the control group. However, the difference was not significant. Conclusion Bamlanivimab decreased hospital and ICU admissions in cancer patients. In addition, bamlanivimab reduced oxygen requirement and the risk of hypoxia and progression to severe disease in this patient population. Disclosures Samuel L. Aitken, PharmD, MPH, BCIDP, Melinta Therapeutoics (Individual(s) Involved: Self): Consultant, Grant/Research Support


Figure 1. Patient Section.
Results. Mortality rate: no difference (2.1% vs 1.8%, p=0.84). 30 day post-discharge ED visit: twice more likely in the abbreviated RDV group as compared to the group receiving the standard duration (16.1% vs 8.5%, p=0.03). 30 day readmission: almost 10 times more likely in the abbreviated RDV group as compared to the group receiving the standard duration (11.9% vs 1.2%, p=< 0.001).

Conclusion.
Though there is no difference in 30 day mortality rate, the patients who received the abbreviated RDV course are twice more likely to have ER visit and 10 times more likely to have readmission within 30 day post discharge despite more patients in the abbreviated course receiving steroids. The findings suggest that completing an at least 5-day course of RDV may be beneficial even in patients who demonstrate a clinical response earlier in course.
Disclosures. Background. Bamlanivimab is a monoclonal antibody that was granted an emergency use authorization by the US Food and Drug Administration in November 2020 for patients with mild to moderate coronavirus disease 2019 . It initially showed promising results with decreasing hospitalizations and return emergency department visits in immunocompetent patients. We evaluated the role of bamlanivimab in the cancer patient population.

Methods.
We conducted a retrospective matched study of all cancer patients diagnosed with mild to moderate COVID-19 who received bamlanivimab in our acute cancer care center (ACCC) from December 2020 to February 2021. These patients were compared to a control group of cancer patients who presented to our ACCC and were diagnosed with mild to moderate COVID-19 from March to November 2020 before the introduction of bamlanivimab. Control patients were matched by age and underlying malignancy. All patients had a baseline oxygen saturation ≥ 94% and an absolute neutrophil count > 500 mm 3 . Demographics, clinical characteristics, and outcome that included COVID-related admissions, oxygen desaturation, ICU admission and 30-day mortality were compared in both groups.
Results. A total of 108 patients were analyzed with 54 patients in each group, of which 59% consisted of hematologic malignancies, and 33% were ≥ 65 years. The presenting symptoms were similar in both groups and mainly consisted of cough, fever, and dyspnea. Patients who received bamlanivimab were less likely to be admitted to the hospital (24% vs. 91%; p< 0.0001), experience oxygen desaturation < 94% during follow-up (11% vs 44%; p=0.0001), require oxygen supplement (7% vs. 44%; p< 0.0001), or be admitted to the ICU (4% vs 15%; p=0.046). No 30-day mortality was observed in the bamlanivimab group with 2 (4%) occurring in the control group. However, the difference was not significant.
Conclusion. Bamlanivimab decreased hospital and ICU admissions in cancer patients. In addition, bamlanivimab reduced oxygen requirement and the risk of hypoxia and progression to severe disease in this patient population.
Disclosures. Samuel L. Aitken, PharmD, MPH, BCIDP, Melinta Therapeutoics (Individual(s) Involved: Self): Consultant, Grant/Research Support Background. Molnupiravir (MOV, MK-4482, EIDD-2801) is an orally administered prodrug of N-hydroxycytidine (NHC, EIDD-1931), a nucleoside with broad antiviral activity against a range of RNA viruses. MOV acts by driving viral error catastrophe following its incorporation by the viral RdRp into the viral genome. Given its mechanism of action, MOV activity should not be affected by substitutions in the spike protein present in SARS-CoV-2 variants of concern which impact efficacy of therapeutic neutralizing antibodies and vaccine induced immunity. We characterized MOV activity against variants by assessing antiviral activity in vitro and virologic response from the Phase 2/3 clinical trials (MOVe-In, MOVe-Out) for treatment of COVID-19.

Molnupiravir Maintains Antiviral Activity Against SARS-CoV-2 Variants In Vitro and in Early Clinical Studies
Methods. MOV activity against several SARS-CoV-2 variants, was evaluated in an in vitro infection assay. Antiviral potency of NHC (IC50) was determined in Vero E6 cells infected with virus at MOI ~0.1 by monitoring CPE. Longitudinal SARS-CoV-2 RNA viral load measures in participants enrolled in MOVe-In and MOVe-Out were analyzed based on SARS-CoV-2 genotype. Sequences of SARS-CoV-2 from study participants were amplified from nasal swabs by PCR and NGS was performed on samples with viral genome RNA of >22,000 copies/ml amplified by primers covering full length genome with Ion Torrent sequencing to identify clades represented in trial participants. SARS-CoV-2 clades were assigned using clade.nextstrain.org.
Results. In vitro, NHC was equally effective against SARS-CoV-2 variants B.1.1.7 (20I), B.1351 (20H), and P1 (20J), compared with the original WA1 (19B) isolate. In clinical trials, no discernable difference was observed in magnitude of viral response measured by change from baseline in RNA titer over time across all clades represented including 20A through 20E and 20G to 20I. No participants at the time of the study presented with 20F, 20J, or 21A.  Background. Monoclonal antibody (Mab) infusions have reduced hospitalization and mortality among higher risk patients with mild to moderate COVID-19 symptoms. Using an interdisciplinary team approach, we created a clinical team to proactively screen and outreach patients with COVID-19 to equitably offer Mab.

Conclusion. Distribution of clades in participants in
Methods. From December 28, 2020 -May 3, 2021, a clinical team consisting of an Infectious disease pharmacist and physician, reviewed each outpatient with a positive SARS-CoV-2 PCR test at the Atlanta VA Healthcare System (AVAHCS) daily. The clinical team used the published Emergency Use Authorization criteria to determine eligibility. Eligible patients were prioritized using the Veterans Health Administration (VACO) Index for COVID-19 Mortality, which estimates the risk of 30-day mortality after COVID-19 infection using pre-COVID-19 health status (Figure 1). Eligible patients were contacted via telephone to confirm eligibility and obtain verbal consent. We performed SARS-CoV-2 IgG antibody tests when possible prior to Mab infusion, but results did not preclude Mab receipt. Telehealth follow-up occurred at 1-and 7-days post infusion.