Citations

Background: Acute Respiratory Distress Syndrome (ARDS) is caused by non-cardiogenic pulmonary edema and occurs in critically ill patients. It is one of the fatal complications observed among severe COVID-19 cases managed in intensive care units (ICU). Supportive lung-protective ventilation and prone positioning remain the mainstay interventions. Purpose: We describe the severity of ARDS, clinical outcomes, and management of ICU patients with laboratory-confirmed COVID-19 infection in multiple Saudi hospitals. Methods: A multicenter retrospective cohort study was conducted of critically ill patients who were admitted to the ICU with COVID-19 and developed ARDS. Results: During our study, 1154 patients experienced ARDS: 591 (51.2%) with severe, 415 (36.0%) with moderate, and 148 (12.8%) with mild ARDS. The mean sequential organ failure assessment (SOFA) score was significantly higher in severe ARDS with COVID-19 (6 ± 5, p = 0.006). Kaplan–Meier survival analysis showed COVID-19 patients with mild ARDS had a significantly higher survival rate compared to COVID-19 patients who experienced severe ARDS (p = 0.023). Conclusion: ARDS is a challenging condition complicating COVID-19 infection. It carries significant morbidity and results in elevated mortality. ARDS requires protective mechanical ventilation and other critical care supportive measures. The severity of ARDS is associated significantly with the rate of death among the patients.

AbstractThe inclusion of ancestrally diverse participants in genetic studies can lead to new discoveries and is important to ensure equitable health care benefit from research advances. Here, members of the Ethical, Legal, Social, Implications (ELSI) committee of the International Genetic Epidemiology Society (IGES) offer perspectives on methods and analysis tools for the conduct of inclusive genetic epidemiology research, with a focus on admixed and ancestrally diverse populations in support of reproducible research practices. We emphasize the importance of distinguishing socially defined population categorizations from genetic ancestry in the design, analysis, reporting, and interpretation of genetic epidemiology research findings. Finally, we discuss the current state of genomic resources used in genetic association studies, functional interpretation, and clinical and public health translation of genomic findings with respect to diverse populations.

SummaryPatients with chronic lymphocytic leukaemia (CLL) disease progression on ibrutinib or after sequential ibrutinib and venetoclax‐based treatments (double‐refractory) have poor outcomes. In this retrospective study, we analysed outcomes with combined ibrutinib and venetoclax treatment in these groups of patients. The median treatment‐free and overall survival for 22 patients with prior progression on ibrutinib (venetoclax‐naïve) were 23.7 and 47.1 months respectively. In 11 patients with double‐refractory CLL, the median treatment‐free and overall survival were 11.2 and 27.0 months respectively. The combination of ibrutinib and venetoclax may help bridge the current gap in options for patients with disease refractory to the most commonly used novel agents.

The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemotherapy-free option for patients with previously untreated or relapsed/refractory CLL/SLL. Undetectable minimal residual disease after the end of treatment is emerging as an important predictor of progression-free and overall survival for patients treated with fixed-duration BCL-2 inhibitor-based treatment. These NCCN Guidelines Insights discuss the updates to the NCCN Guidelines for CLL/SLL specific to the use of chemotherapy-free treatment options for patients with treatment-naïve and relapsed/refractory disease.

8057 Background: Following autologous hematopoietic stem cell transplant (auto HCT), maintenance therapies improve survival, reduce relapse risk in multiple myeloma (MM), and are the de facto standard-of-care. However, clinical trials have shown an increased risk of second primary malignancies (SPM) with maintenance therapy, including second hematological malignancies (SHM). We examined data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to evaluate the impact of SPM on progression-free (PFS) and overall survival (OS) and the utilization of allogeneic HCT in patients with therapy-related myeloid neoplasms (t-MN). Methods: Adult patients (pts) with MM who underwent first auto HCT in the United States with a melphalan conditioning regimen from 2011-2018 and subsequently received maintenance therapy were included (N=3948). The primary endpoint of interest was the impact of SPM and SHM on OS. Multivariate analytic (MVA) modelling was applied, accounting for competing risks while integrating significant covariates to determine the impact of SPM on PFS and OS. Finally, we studied the utilization and survival following allogeneic HCT for SHM. Results: Baseline characteristics were similar between the two groups. Maintenance regimens used were lenalidomide (2836, 72%), bortezomib (370,9 %) or lenalidomide + bortezomib (372, 9%) based combinations. At a median follow up of 37 months, 175 (5%) pts developed SPM, including 112 (64%) solid 36 (21%) myeloid, and 27 (15%) lymphoid cancers. In MVA, the development of SPM and SHM was associated with an inferior PFS (HR 2.62, P<0.001 and HR 5.01, P<0.001, respectively) and OS (HR 3.85, P<0.001 and 8.13, P<0.001, respectively). The two commonest causes of death were MM (42%) and SPM (30%) for those developing SPM. Similarly, MM (53%) and SHM (18%) were the two commonest causes of death for those developing SHM. Nine (14%,5 t-MDS and 4 t-AML) of 63 patients with SHM underwent an allogeneic HCT. Patients undergoing allogeneic HCT were more likely to have Karnofsky score ≥90 (100% vs. 50%, P=0.02) compared to those who did not. One year survival from allo SCT was 66.7% (CI 34.6-92%). Conclusions: The three-year cumulative incidence of SPM was 3.3 (2.6-4)% in this large contemporaneous CIBMTR cohort. Disease relapse remains the primary cause of death in MM patients who develop SPM or SHM. Given the median OS for MM is now > 10 years, longer follow-up is needed to assess the SPM and SHM risks with maintenance therapy post-auto HCT.

8054 Background: The introduction of immunomodulatory agents, proteasome inhibitors, and autologous stem cell transplantation (ASCT) has improved outcomes for patients with multiple myeloma (MM), but those with high risk MM (HRMM) have a poor long-term prognosis. Herein we provide survival outcomes on the first randomized trial in newly diagnosed HRMM, S1211, to follow-up on the previously reported progression-free survival (PFS) (NCT01668719, Usmani SZ et al, Lancet Haem 2021). Methods: S1211 is a randomized phase II trial comparing 8 cycles of lenalidomide, bortezomib and dexamethasone (RVd) induction followed by dose-attenuated RVd maintenance until disease progression with or without elotuzumab (RVd-Elo). Stem cell collection was allowed, but ASCT was deferred until progression. HRMM was defined by one of the following: gene expression profiling high-risk (GEPhi), t(14;16), t(14;20), del(17p), amplification 1q21, primary plasma cell leukemia (pPCL), or elevated serum LDH (> 2X ULN). Median PFS was the primary endpoint, using a one-sided stratified log-rank test at a one-sided significance level of 0.1. Secondary endpoints included overall response rate (ORR), adverse events (AE), serious adverse events (SAE) and OS. Response was assessed using the IMWG 2009 criteria. Results: S1211 enrolled 103 evaluable patients, RVd n=54, RVd-Elo n=49. 74% had ISS II/III, 48% amp1q21, 38% del(17p), 11% t(14;16), 9% GEPhi, 7% pPCL, 5% t(14;20) and 4% elevated LDH (17% >1 feature). With median follow-up of 72 months (mos.), no difference in median PFS was observed [RVd-Elo=29 mos., RVd= 34 mos., HR = 1.11 (80% CI=0.82, 1.49, p=0.66]. No difference in OS was observed [RVd-Elo = median not reached (NR), RVd= 68 mos., HR = 0.85 (80% CI: 0.59, 1.23), p-value = 0.58]. 76% pts had >Grade 3 AEs, no differences in the safety profile were observed. Amongst patients with gain/amp 1q21, median PFS was [RVd-Elo=31 mos., RVd= 37 mos., HR = 1.48 (80% CI= 0.95, 2.31), p=0.25], median OS was [RVd-Elo = 61 mos., RVd= 68 mos., HR = 1.23 (80% CI: 0.72, 2.10), p-value = 0.63]. In patients with del(17p), median PFS was RVd-Elo=41 mos., RVd= 30 mos.[HR = 0.98 (80% CI= 0.60, 1.58), p=0.95], median OS RVd-Elo = NR, RVd= 72 mos., [HR = 0.77 (80% CI: 0.40, 1.48), p-value = 0.61]. Conclusions: In the first randomized HRMM study reported to date, the addition of Elo to RVd induction and maintenance did not improve PFS and OS with a median follow-up of 6 years. Although the median PFS for Del17p subgroup on RVd-Elo arm is higher than RVd, it did not achieve statistical significance. The PFS and OS observed for gain/amp 1q21 and del17p in the RVd control arm may serve as important benchmarks for future enrichment design HRMM clinical trials. The PFS and OS in both arms of the study exceeded the original statistical assumptions and support the role for PI/IMiD combination induction/maintenance therapy for this population. Clinical trial information: NCT01668719.