ABSTRACT
SARS-CoV-2 viral cause infection called COVID-19 was initially reported in China has resulted in a pandemic because it has spread in over 210 countries. This review summarized pathophysiology, clinical features, diagnosis, and COVID 19. The spread of SARS-CoV-2 viral infections is a matter of concern because of a mutant variant of virus. The COVID-19 infection is having 14 days incubation period. Fever, sore throat, cough, severe headache, breathlessness, myalgia and weakness are common symptoms observed in patients with COVID-19. Steps of replication of SARS-CoV-2 virus are attachment, penetration, uncoating, replication, assembly and release. Patients' screening tests are complete blood count, C-reactive protein (CRP) and erythrocyte, sedimentation rate (ESR), D-dimer, serum ferritin, and others. The reverse transcription-polymerase chain reaction (RT-PCR) is the important diagnostic test of molecular genetic assays for detecting viral RNA. In-Patient of COVID 19 CT scan shows ground-glass opacities with or without consolidations in lung regions. In CT scan, standardized assessment scheme is CORAD classification and assessment of lung involvement can be done CT severity score index. Management: Management of COVID -19 starts with supportive and symptomatic treatment. As soon as the patient gets an infection, the patient should maintain adequate isolation to prevent transmission to other contacts, patients, and healthcare workers. Mild infection can be managed at home with counseling about danger signs. The patient should be advised to maintain hydration and nutrition, and symptomatic treatment should be given. A variety of therapeutic options currently include remdesivir, favipiravir, bamlanivimab / etesevimab, casirivimab / imdevimab dexamethasone, baricitinib, tocilizumab are available.
ABSTRACT
Background: Isocitrate dehydrogenase 2 (IDH2) mutations occur in 5% of patients (pts) with MDS. Enasidenib (ENA) is a selective oral inhibitor of the mutant IDH2 enzyme with single-agent activity in relapsed/refractory acute myeloid leukemia (AML). We report the results of the open label phase II study designed to evaluate the efficacy and tolerability of ENA, as monotherapy or in combination with azacitidine (AZA) in pts with higher-risk IDH2-mutated MDS (NCT03383575). Methods: Pts with higher-risk [Revised International Prognostic Scoring System risk > 3 or high molecular risk (HMR)] MDS/CMML or LB AML naïve to hypomethylating agents (HMA) received ENA100 mg orally daily for 28 d of each 28-d cycle + AZA 75 mg/m2 IV or SC on d 1-7 of each cycle (ENA+AZA), and pts with refractory or progressive MDS to prior HMA therapy received ENA alone (ENA), in 28-d cycles until unacceptable toxicity, relapse, transformation to AML, or progression. The primary endpoint was overall response rate (ORR) [complete remission (CR), marrow CR (mCR), partial remission (PR) and hematologic improvement (HI)]. Other endpoints include safety, and survival outcomes. Results: 48 pts received ENA+AZA (n = 26) or ENA (n = 22). The median age was 73 yrs (range, 46-83). Most pts (72%) had HMR: ASXL1 (39%), and RUNX1 (17%). Median number Tx cycles was 4 (2-32) in the ENA+AZA, and 7 (1-23) in the ENA arm. Common Tx-related grade 3-4 AEs in the ENA+AZA arm were neutropenia (64%), thrombocytopenia (28%), and anemia (8%);these occurred in 10%, 0%, and 5%, in the ENA arm. Grade 3-4 infections occurred in 32% (ENA+AZA) and 14% (ENA). IDH differentiation syndrome occurred in 3 pts (12%) in the ENA+AZA and 5 pts (24%) in the ENA arm. Two deaths occurred during the initial 60 d, both unrelated to study and due to COVID. In response-evaluable pts (n=46), ORR was 84% (n = 21/25;24% CR + 8% PR+44% mCR+ 8% HI] in the treatment naïve ENA+AZA and 43% (n = 9/21;24% CR+5%PR+5% mCR+10% HI) in the HMA failure ENA arm (Table). Most common reason for Tx discontinuation was disease progression (ENA+AZA 20%, ENA 33%).5 pts (20%) received HCT in the ENA+AZA and 1 (5%) in the ENA arm. 7 pts in the ENA+AZA and 5 in the ENA arm were ongoing at data cutoff (Dec 31, 2020). After a median follow up of 12.6 mo, median OS was 32.2 mo in the ENA+AZA and 21.3 mo in the ENA arm. Conclusions: ENA is well tolerated and shows promising efficacy in IDH2-mutated higher risk MDS. Follow up and accrual is ongoing to better define duration and biomarkers of response.