Introduction Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, with an estimated 18,740 new cases of CLL in 2023. This study describes current treatment patterns, healthcare resource use (HCRU) and patient voice in patients with CLL in the US using a novel patient-centered database. Methods A retrospective study using data from the Inspire Integrated Analytical Database (IIAD), which links Inspire patient voice with electronic health records (EHR) and medical and pharmacy claims through HIPAA-compliant tokenization. Patients worldwide with various conditions join Inspire's online health community and contribute their experience through online posts and survey participation (see Figure 1). Medical and pharmacy claims in IIAD range from 2013 to present, with EHR data ranging from 2010 to present. Inspire members were included in the study if they resided in the US and had at least two diagnoses for CLL (ICD-10 codes C91.10, C91.11 or C91.12) on at least two distinct dates that were between 30 and 60 days of each other. The first observed CLL diagnosis date was considered the index date. Patients with an index date on or before 6/30/2022 were included in the analysis. Baseline patient characteristics and HCRU were evaluated. CLL treatment was identified from medical and pharmacy claims. Online posts which CLL patients have viewed at least once were evaluated. Post topics are defined as named entities recognized by Inspire's Natural Language Processing (NLP) engine from all of the discussion posts written by any Inspire members. Descriptive statistics were reported. Results A total of 331 CLL patients were identified in the online community with linked claims and EHR data. Median follow-up time was 59 months from index date. The median age at diagnosis was 73 and 49% of patients were female. Patients were geographically represented across the US. 63% had ≥100 claims from a median of 25 care sites across 33 providers. During follow-up a median of 3 hospitalizations per patient were observed. 5% of patients experienced a Richter's transformation and 22% developed a secondary malignancy (lung, gastrointestinal or skin cancer) after their index CLL date. 104 patients (31%) of the cohort had available data for CLL treatment. Median time to first CLL treatment was 11.7 months (range: 1 day - 86.8 months). Ibrutinib was the most common medication (n = 43), followed by venetoclax (n = 30) and rituximab (n = 20). The 5 most common topics viewed by patients on the Inspire community website included: skin, side-effect, muscle, biopsy, and infection. Prior to starting therapy, searches on the Inspire platform included terms such as “imbruvica,” “calquence,” and “living with CLL.” Searches after CLL treatment revealed that patients broadened search terms to include other cancer types such as “pelvic cancer,” “liver metastasis” and “melanoma.” Conclusions This report utilized a unique dataset that integrates patient voice with EHR and claims data to describe clinical characteristics, and treatment patterns of CLL patients drawn from the patient-centered Inspire digital health community. The online population had a median age of 73 at diagnosis, consistent with the average age of CLL diagnosis (70 yrs.). Patients in our cohort initiated treatment approximately 1 year after CLL diagnosis. Online activities on the Inspire platform demonstrated that CLL patients are engaged in searching and reading discussion posts concerning the impact of side effects and treatments on quality of life, and emphasized emerging concerns about the potential impact of secondary malignancies. Future real-world studies need to integrate patient voice to fully understand the consequences of a cancer diagnosis.

Background: Myelodysplastic Syndromes (MDS) are a heterogeneous group of marrow failure diseases whose prognosis and treatments are guided by marrow morphology, degrees of cytopenias, and genetic changes. Due to the complexity of the disorder, combined with the advanced age and frailty of most patients, conveying crucial information for shared decision-making poses challenges. Despite efforts designed to enhance communication, there is limited understanding of these initiatives' effectiveness. Methods: The Cancer Experience Registry® is an ongoing online research study conducted by the Cancer Support Community that seeks to uncover the emotional, physical, practical, and financial impact of cancer from the patient's perspective. In association with the MDS Foundation, this observational, cross-sectional study enrolls patients with MDS who provide socio-economic and clinical history, supplemented with information related to their MDS diagnosis. Frequencies and descriptive statistics are presented. Results: Between December 2021 and February 2023, 140 MDS patients joined the registry. By self-report, the study population was 51% female and 91% non-Hispanic white with a median age 61 (range 34-93). Like other cancer disease cohorts in the online registry, the MDS population was highly educated (81% attending college and 31% obtaining advanced degrees). 18% reported gross annual incomes less than $40,000 but 29% reported incomes above $80,000 (with 25% not responding). 70% were retired, 15% were still employed and 11% considered themselves unemployed due to disability. 41% of the patients were newly diagnosed (disease duration less than 1 year) and an additional 19% had MDS for less than 2 years. Interestingly, 24% carried a diagnosis of MDS for more than 6 years (including 11% reporting >10 years duration). 51% were in active treatment, 18% were between therapies, and 26% had never received any MDS-directed therapy. 76% self-reported a primary MDS diagnosis and 7% secondary MDS, with the remainder unsure. 33% of the respondents did not know their WHO morphologic subtype with 13% stating that they were never informed and 16% unsure if they were told this information. Similarly, although the IPSS-R is a critical determinant of prognosis and informs treatment decisions, 23% could not recall this score with 11% stating that they were not told their IPSS-R and 9% not sure if they were informed. Among 118 respondents, only 18% could remember their genetic testing results. 120 participants answered questions regarding whether they received additional assistance with MDS-related information and when this was provided. By patient recall, general information about MDS was provided to 78% at the time of diagnosis and an additional 5% after starting treatment. Help in understanding the WHO subtype and IPSS-R was remembered by 41% and 52%, respectively, at the time of diagnosis, and 8% and 9% after starting treatment. A third could not recall being informed about genetic mutational testing. Information about the possibility of MDS transforming into AML was not recalled by 21%. Information about transfusion support was remembered by 46% at the time of diagnosis and 17% after starting treatment (with 29% stating that they had not received information about transfusions and 8% unable to recall). A discussion about transplant options was remembered by 67%. Although a quarter of patients have never received therapy, 32% stated that they had never had a discussion of treatment options and an additional 6% were unsure if a discussion had occurred. A discussion about specific MDS medications was remembered by 51% at the time of diagnosis and 19% only after the start of therapy, with 30% not recalling any assistance in understanding medication options. Conclusions: Based on the early results of the Cancer Experience Registry® derived from a cohort of highly educated and motivated MDS patients, it appears that effective communication about MDS and treatment options is suboptimal. A significant proportion of respondents were unable to recall information about their diagnosis critical to informed shared decision-making. Given the complexities of an MDS diagnosis, additional efforts to educate patients are necessary. Patient support organizations, such as the Cancer Support Community and the MDS Foundation, can serve as valuable educational resources.

Among patients with triple-negative breast cancer (TNBC), several studies have suggested that deregulated microRNA (miRNA) expression may be associated with a more aggressive phenotype. Although tumor molecular signatures may be race- and/or ethnicity-specific, there is limited information on the molecular profiles in women with TNBC of Hispanic and Latin American ancestry. We simultaneously profiled TNBC biopsies for the genome-wide copy number and miRNA global expression from 28 Latina women and identified a panel of 28 miRNAs associated with copy number alterations (CNAs). Four selected miRNAs (miR-141-3p, miR-150-5p, miR-182-5p, and miR-661) were validated in a subset of tumor and adjacent non-tumor tissue samples, with miR-182-5p being the most discriminatory among tissue groups (AUC value > 0.8). MiR-141-3p up-regulation was associated with increased cancer recurrence; miR-661 down-regulation with larger tumor size; and down-regulation of miR-150-5p with larger tumor size, high p53 expression, increased cancer recurrence, presence of distant metastasis, and deceased status. This study reinforces the importance of integration analysis of CNAs and miRNAs in TNBC, allowing for the identification of interactions among molecular mechanisms. Additionally, this study emphasizes the significance of considering the patients ancestral background when examining TNBC, as it can influence the relationship between intrinsic tumor molecular characteristics and clinical manifestations of the disease.

Background Individuals with comorbid conditions have been disproportionately affected by COVID-19. Since regulatory trials of COVID-19 vaccines excluded those with immunocompromising conditions, few patients with cancer and autoimmune diseases were enrolled. With limited vaccine safety data available, vulnerable populations may have conflicted vaccine attitudes. Objective We assessed the prevalence and independent predictors of COVID-19 vaccine hesitancy and acceptance among individuals with serious comorbidities and assessed self-reported side effects among those who had been vaccinated. Methods We conducted a cross-sectional, 55-item, online survey, fielded January 15, 2021 through February 22, 2021, among a random sample of members of Inspire, an online health community of over 2.2 million individuals with comorbid conditions. Multivariable regression analysis was utilized to determine factors independently associated with vaccine hesitancy and acceptance. Results Of the 996,500 members of the Inspire health community invited to participate, responses were received from 21,943 individuals (2.2%). Respondents resided in 123 countries (United States: 16,277/21,943, 74.2%), had a median age range of 56-65 years, were highly educated (college or postgraduate degree: 10,198/17,298, 58.9%), and had diverse political leanings. All respondents self-reported at least one comorbidity: cancer, 27.3% (5459/19,980); autoimmune diseases, 23.2% (4946/21,294); chronic lung diseases: 35.4% (7544/21,294). COVID-19 vaccine hesitancy was identified in 18.6% (3960/21,294), with 10.3% (2190/21,294) declaring that they would not, 3.5% (742/21,294) stating that they probably would not, and 4.8% (1028/21,294) not sure whether they would agree to be vaccinated. Hesitancy was expressed by the following patients: cancer, 13.4% (731/5459); autoimmune diseases, 19.4% (962/4947); chronic lung diseases: 17.8% (1344/7544). Positive predictors of vaccine acceptance included routine influenza vaccination (odds ratio [OR] 1.53), trust in responsible vaccine development (OR 14.04), residing in the United States (OR 1.31), and never smoked (OR 1.06). Hesitancy increased with a history of prior COVID-19 (OR 0.86), conservative political leaning (OR 0.93), younger age (OR 0.83), and lower education level (OR 0.90). One-quarter (5501/21,294, 25.8%) had received at least one COVID-19 vaccine injection, and 6.5% (1390/21,294) completed a 2-dose series. Following the first injection, 69.0% (3796/5501) self-reported local reactions, and 40.0% (2200/5501) self-reported systemic reactions, which increased following the second injection to 77.0% (1070/1390) and 67.0% (931/1390), respectively. Conclusions In this survey of individuals with serious comorbid conditions, significant vaccine hesitancy remained. Assumptions that the most vulnerable would automatically accept COVID-19 vaccination are erroneous and thus call for health care team members to initiate discussions focusing on the impact of the vaccine on an individual’s underlying condition. Early self-reported side effect experiences among those who had already been vaccinated, as expressed by our population, should be reassuring and might be utilized to alleviate vaccine fears. Health care–related social media forums that rapidly disseminate accurate information about the COVID-19 vaccine may play an important role.

Introduction Tyrosine kinase inhibitors (TKIs) are commonly used as first-line therapy for the treatment of patients with chronic myeloid leukemia in the chronic phase (CML-CP). Molecular response is monitored regularly after initiating TKI therapy and less frequently after achieving BCR::ABL1 ≤ 0.1%. Although responses to TKIs have been extensively evaluated in clinical trials, utilization of molecular testing and clinical response associated with TKI therapy is not as well understood in real-world settings. SIMPLICITY (NCT01244750) is a prospective observational study assessing TKI use, molecular testing patterns, and clinical response in patients with CML-CP in routine clinical practice. Methods The SIMPLICITY study followed patients with CML-CP from routine clinical practice who received first-line treatment with the first-generation TKI imatinib (IM) or second-generation TKIs dasatinib (DAS) or nilotinib (NIL) in the USA and Europe. As this was an observational study, molecular testing was performed at the discretion of the treating team without directives from the study protocol. The cumulative proportion of US patients who underwent ≥ 1 molecular test as well as the rates of major molecular response (MMR; BCR::ABL1 ≤ 0.1%) and deep (4.5-log) molecular response (MR4.5; BCR::ABL1 < 0.0032%) were evaluated through 3 and 6 months, and yearly through 5 years, after starting TKI treatment. Patients were stratified by index TKI (IM or DAS/NIL). Descriptive statistics are presented. Results At data cutoff (January 28, 2020), a total of 810 prospective US patients were enrolled and included in this analysis, of whom 244 received IM and 566 received DAS/NIL. The median age (range) at diagnosis was 56 (18-91) years (IM, 58 [18-90] years; DAS/NIL, 55 [19-91] years). A total of 796 (98.3%) patients were followed through 3 months from the start of index TKI treatment, 792 (97.8%) through 6 months, 762 (94.1%) through 1 year, 704 (86.9%) through 2 years, 652 (80.5%) through 3 years, 590 (72.8%) through 4 years, and 538 (66.4%) through 5 years. Of those followed, the overall proportion of patients tested for molecular response ranged from 20.7% through 3 months to 92.2% through 5 years (Figure). The proportion of assessed patients who achieved MMR at least once increased over time; MMR was achieved in 15.8% of patients assessed through 3 months (IM, 11.1%; DAS/NIL, 17.1%), 35.0% through 6 months (IM, 28.7%; DAS/NIL, 36.8%), 58.2% through 1 year (IM, 51.6%; DAS/NIL, 60.5%), 77.4% through 2 years (IM, 72.9%; DAS/NIL, 79.2%), 86.6% through 3 years (IM, 84.8%; DAS/NIL, 87.3%), 92.5% through 4 years (IM, 90.6%; DAS/NIL, 93.4%), and 95.4% through 5 years (IM, 95.9%; DAS/NIL, 95.2%). The proportion of patients who achieved MR4.5 at least once also increased over time; MR4.5 was achieved in 6.1% of patients assessed through 3 months (IM, 2.8%; DAS/NIL, 7.0%), 15.9% through 6 months (IM, 9.2%; DAS/NIL, 17.9%), 32.5% through 1 year (IM, 23.4%; DAS/NIL, 35.6%), 50.2% through 2 years (IM, 41.3%; DAS/NIL, 53.6%), 63.8% through 3 years (IM, 54.9%; DAS/NIL, 67.4%), 73.8% through 4 years (IM, 67.9%; DAS/NIL, 76.3%), and 79.2% through 5 years (IM, 75.9%; DAS/NIL, 80.6%). Among all 810 enrolled patients, 473 (58.4%) and 393 (48.5%) achieved MMR and MR4.5, respectively, and remained in the study through 5 years. Mean (standard deviation) time from index TKI to best response in tested patients was 2.4 (0.5) months among patients assessed through 3 months and 24.4 (15.4) months among those assessed through 5 years. Conclusions At 5-year follow-up in US patients from the SIMPLICITY study, there was a consistent increase in the proportion of assessed patients who achieved MMR and MR4.5 over time for all patients treated with TKIs, with the caveat that patients who remained on treatment at each subsequent time point were more likely to respond. In general, a consistently higher proportion of patients treated with DAS/NIL achieved MR4.5 across the time points assessed compared with IM in this non-controlled study. Further studies evaluating molecular response to IM, DAS, NIL, and other TKIs beyond 5 years can help delineate further differences in outcomes and determine whether molecular testing frequency correlates with outcomes. Study support This study was funded by Bristol Myers Squibb. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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.

BackgroundThe COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments.MethodsElectronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined.ResultsNeither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events.ConclusionAdministration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.

Genomic biomarkers inform treatment in multiple myeloma (MM), making patient clinical data a potential window into MM biology. We evaluated de novo MM patients for associations between specific MM cytogenetic patterns and prior cancer history. Analyzing a MM real-world dataset, we identified a cohort of 1769 patients with fluorescent in situ hybridization cytogenetic testing at diagnosis. Of the patients, 241 (0.14) had histories of prior cancer(s). Amplification of the long arm of chromosome 1 [amp(1q)] varied by prior cancer history (0.31 with prior cancer vs 0.24 without; 2-sided P=.02). No other MM translocations, amplifications, or deletions were associated with prior cancers. Amp(1q) and cancer history remained strongly associated in a logistic regression adjusting for patient demographic and disease attributes. The results merit follow-up regarding carcinogenic treatment effects and screening strategies for second malignancies. Broadly, the findings suggest that analyses of patient-level phenotypic-genomic real-world dataset may accelerate cancer research through hypothesis-generating studies.

Background: CPX-351 is a liposomal encapsulation of daunorubicin and cytarabine in a 1:5 molar ratio. In a randomized phase 3 study (CPX-351-301) conducted in older adults (60 to 75 years old) with newly diagnosed, high-risk and/or secondary AML, CPX-351 induction therapy was superior to standard 7+3 with improved rates of complete remission (CR) and overall survival (OS). In both older adults and high-risk AML, allogeneic hematopoietic cell transplantation (HCT) is frequently the preferred post-remission strategy owing to the high rates of relapse and poor overall survival with conventional chemotherapy approaches. After a median follow-up of 20.7 months, the primary pre-planned analysis found that more patients randomized to CPX-351 underwent HCT and an exploratory landmark survival analysis from the time of HCT favored CPX-351 (HR = 0.46 [95% CI: 0.24, 0.89]; one-sided P = 0.009). However, the initial protocol did not collect data related to HCT and the basis for improved HCT outcomes with CPX-351 was previously unknown. Here we present a detailed analysis of HCT outcomes in patients enrolled in the CPX-351-301 study with 5-years of follow-up. Methods: Patients age 60 to 75 years with high-risk and/or secondary AML were randomized in a 1:1 fashion to receive CPX-351 or 7+3 as induction and consolidation chemotherapy (Lancet J et al, JCO 2018). The protocol was amended to collect additional HCT-specific information, including donor and HCT characteristics and post-HCT outcomes, including rates of relapse and GVHD. Post-HCT outcomes including relapse, GVHD, and death were analyzed as competing events. Results: Of 309 randomized patients in the CPX-351-301 study, more patients achieved CR/CRi with CPX-351 vs 7+3 (48% vs 33%) allowing more patients to proceed to HCT (35% vs 25%) and more patients to proceed to HCT in remission (CPX-351: 41/73 [56%]; 7+3: 24/52 [46%]). The median age was 66 years with CPX-351 vs 65 years with standard induction among the transplanted cohorts; 16 patients in the CPX-351 transplanted arm were over the age of 70 compared to only 6 in the 7+3 arm. Other pre-HCT patient characteristics were balanced between the CPX-351 and 7+3 groups, including ECOG performance status (8% vs 5% with ECOG PS of 2), HCT-CI (median 4 vs 3), donor type (matched unrelated donor 49% vs 49%), and conditioning regimen intensity (myeloablative [17% vs 13%] vs reduced-intensity conditioning [43% vs 46%]). The Kaplan-Meier-estimated 3-year survival rate among transplanted patients was 56% with CPX-351 vs 23% with 7+3 (Figure 1A). The differences in survival consistently favored CPX-351 across patient age, AML subtype, disease status, donor type, and conditioning intensity (Figure 1B). Differences in OS were driven by a large reduction in non-relapse mortality (HR = 0.42 [95% CI: 0.21, 0.86]; Figure 1D). The cumulative incidence of acute GVHD with death as a competing event at 6 months from HCT date was 0.49 (95% CI: 0.35, 0.62) in the CPX-351 arm and 0.38 (95% CI: 0.23, 0.53) in the 7+3 arm. Conclusions: Analysis of HCT outcomes in patients enrolled in the CPX-351-301 study demonstrated that treatment with CPX-351 in older adults with high-risk and/or secondary AML resulted in more patients bridged to HCT and more patients transplanted in CR/CRi compared to 7+3, with improved OS in transplanted patients. The pattern of HCT outcomes suggests improved disease control with CPX-351 induction allowing higher HCT rates, but more importantly improved tolerability with less non-relapse mortality; this data supports the development of CPX-351 in other high-risk AML populations in which allogeneic HCT is the preferred post-remission strategy. Figure Disclosures Uy: Genentech: Consultancy; Agios: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Astellas Pharma: Honoraria; Jazz Pharmaceuticals: Consultancy. Lin:Abbvie: Research Funding; Pfizer: Research Funding; Trovagene: Research Funding; Prescient Therapeutics: Research Funding; Tolero Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding; Ono Pharmaceutical: Research Funding; Genetech-Roche: Research Funding; Incyte: Research Funding; Jazz: Research Funding; Mateon Therapeutics: Research Funding; Gilead Sciences: Research Funding; Celyad: Research Funding; Celgene: Research Funding; Bio-Path Holdings: Research Funding; Astellas Pharma: Research Funding; Aptevo: Research Funding. Wieduwilt:Reata Pharmaceuticals: Current equity holder in publicly-traded company; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Shire: Research Funding; Merck: Research Funding; Leadiant: Research Funding; Amgen: Research Funding; Macrogeneics: Research Funding. Ryan:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Faderl:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Lancet:Abbvie: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Astellas Pharma: Consultancy; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; ElevateBio Management: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy.

2621 Background: The rapid development of safe and effective vaccines against SARS-CoV-2 may stem the global COVID-19 pandemic. However, since individuals with cancer were under-represented during clinical vaccine trials, experience with COVID-19 vaccines among cancer patients is limited. Methods: An internet-based survey was conducted January 15 - February 10, 2021 among members of the Inspire online health community. The 63-item survey was emailed to members of the Inspire community who had opted-in for research. Results: Out of 19,152 respondents, 4895 (25%) self-reported a cancer diagnosis. Of these, 1337 (27%) were receiving active therapy. Cancer respondents were 66% female, 77% white, 44% college educated, with a median age range 55-65 years. 88% had solid tumors and 12% hematologic malignancies. 241 (5%) had prior COVID-19 and 148 (3%) thought they had had it but were not tested. Among cancer patients with COVID-19 approximately 30% reported ongoing late symptoms. At the time of survey, 1335 (27%) cancer patients had received a COVID-19 vaccine (Moderna 51% Pfizer-BioNTech 46%, Astra-Zeneca 3%, Other/unknown >1%). Following the first injection, 63% had local adverse events (AEs): injection site pain (51%), swelling (8%), redness (6%), and itching (4%). 34% reported systemic AEs including myalgia (32%), fatigue (18%), headache (12%), joint pain (5%), and chills (5%). 199 (15%) had received the second (booster) vaccination. 76% reported local AEs including pain (69%), swelling (14%), itching (8%), and redness (7%). 67% reported systemic AEs including fatigue (49%), myalgia (30%), headache (29%), chills (23%), fever (16%), joint pain (15%), and nausea (12%). AEs were comparable to the clinical trial results obtained from the general population (fda.gov/media/144245/download & 144434/download). Conclusions: In this internet-based survey drawn from the Inspire online health community 1335 cancer patients reported receiving COVID-19 vaccinations. By self-report the vaccines were well tolerated with AEs patterns mimicking clinical trial results conducted in the general population. These safety results should be reassuring to cancer patients although attention to COVID-19 vaccine efficacy is required (and will be studied during follow-up surveys).[Table: see text]

BACKGROUND:Hydroxychloroquine has not been associated with improved survival among hospitalized COVID-19 patients in the majority of observational studies and similarly was not identified as an effective prophylaxis following exposure in a prospective randomized trial. We aimed to explore the role of hydroxychloroquine therapy in mildly symptomatic patients diagnosed in the outpatient setting.METHODS:We examined the association between outpatient hydroxychloroquine exposure and the subsequent progression of disease among mildly symptomatic non-hospitalized patients with documented SARS-CoV-2 infection. The primary outcome assessed was requirement of hospitalization. Data was obtained from a retrospective review of electronic health records within a New Jersey USA multi-hospital network. We compared outcomes in patients who received hydroxychloroquine with those who did not applying a multivariable logistic model with propensity matching.RESULTS:Among 1274 outpatients with documented SARS-CoV-2 infection 7.6% were prescribed hydroxychloroquine. In a 1067 patient propensity matched cohort, 21.6% with outpatient exposure to hydroxychloroquine were hospitalized, and 31.4% without exposure were hospitalized. In the primary multivariable logistic regression analysis with propensity matching there was an association between exposure to hydroxychloroquine and a decreased rate of hospitalization from COVID-19 (OR 0.53; 95% CI, 0.29, 0.95). Sensitivity analyses revealed similar associations. QTc prolongation events occurred in 2% of patients prescribed hydroxychloroquine with no reported arrhythmia events among those with data available.CONCLUSIONS:In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization. Additional exploration of hydroxychloroquine in this mildly symptomatic outpatient population is warranted.

Background Acute myeloid leukemia (AML) is fatal in elderly patients who are unfit for standard induction chemotherapy. The objective of this study was to evaluate the survival benefit of administering sapacitabine, an oral nucleoside analogue, in alternating cycles with decitabine, a low-intensity therapy, to elderly patients with newly diagnosed AML. Methods This randomized, open-label, phase 3 study (SEAMLESS) was conducted at 87 sites in 11 countries. Patients aged >= 70 years who were not candidates for or chose not to receive standard induction chemotherapy were randomized 1:1 to arm A (decitabine in alternating cycles with sapacitabine) received 1-hour intravenous infusions of decitabine 20 mg/m(2) once daily for 5 consecutive days every 8 weeks (first cycle and subsequent odd cycles) and sapacitabine 300 mg twice daily on 3 consecutive days per week for 2 weeks every 8 weeks (second cycle and subsequent even cycles) or to control arm C who received 1-hour infusions of decitabine 20 mg/m(2) once daily for 5 consecutive days every 4 weeks. Prior hypomethylating agent therapy for preexisting myelodysplastic syndromes or myeloproliferative neoplasms was an exclusion criterion. Randomization was stratified by antecedent myelodysplastic syndromes or myeloproliferative neoplasms, white blood cell count (<10 x 10(9)/L and >= 10 x 10(9)/L), and bone marrow blast percentage (>= 50% vs <50%). The primary end point was overall survival (OS). Secondary end points were the rates of complete remission (CR), CR with incomplete platelet count recovery, partial remission, hematologic improvement, and stable disease along with the corresponding durations, transfusion requirements, number of hospitalized days, and 1-year survival. The trial is registered at ClinicalTrials.gov (NCT01303796). Results Between October 2011 and December 2014, 482 patients were enrolled and randomized to receive decitabine administered in alternating cycles with sapacitabine (study arm, n = 241) or decitabine monotherapy (control arm, n = 241). The median OS was 5.9 months on the study arm versus 5.7 months on the control arm (P = .8902). The CR rate was 16.6% on the study arm and 10.8% on the control arm (P = .1468). In patients with white blood cell counts <10 x 10(9)/L (n = 321), the median OS was higher on the study arm versus the control arm (8.0 vs 5.8 months; P = .145), as was the CR rate (21.5% vs 8.6%; P = .0017). Conclusions The regimen of decitabine administered in alternating cycles with sapacitabine was active but did not significantly improve OS compared with decitabine monotherapy. Subgroup analyses suggest that patients with baseline white blood cell counts <10 x 10(9)/L might benefit from decitabine alternating with sapacitabine, with an improved CR rate and the convenience of an oral drug. These findings should be prospectively confirmed.

Objectives The development of a prognostic mortality risk model for hospitalized COVID-19 patients may facilitate patient treatment planning, comparisons of therapeutic strategies, and public health preparations. Methods We retrospectively reviewed the electronic health records of patients hospitalized within a 13-hospital New Jersey USA network between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2, with follow-up through May 29, 2020. With death or hospital discharge by day 40 as the primary endpoint, we used univariate followed by stepwise multivariate proportional hazard models to develop a risk score on one-half the data set, validated on the remainder, and converted the risk score into a patient-level predictive probability of 40-day mortality based on the combined dataset. Results The study population consisted of 3123 hospitalized COVID-19 patients; median age 63 years; 60% were men; 42% had >3 coexisting conditions. 713 (23%) patients died within 40 days of hospitalization for COVID-19. From 22 potential candidate factors 6 were found to be independent predictors of mortality and were included in the risk score model: age, respiratory rate ≥25/minute upon hospital presentation, oxygenation <94% on hospital presentation, and pre-hospital comorbidities of hypertension, coronary artery disease, or chronic renal disease. The risk score was highly prognostic of mortality in a training set and confirmatory set yielding in the combined dataset a hazard ratio of 1.80 (95% CI, 1.72, 1.87) for one unit increases. Using observed mortality within 20 equally sized bins of risk scores, a predictive model for an individual’s 40-day risk of mortality was generated as -14.258 + 13.460*RS + 1.585*(RS–2.524)^2–0.403*(RS–2.524)^3. An online calculator of this 40-day COVID-19 mortality risk score is available at www.HackensackMeridianHealth.org/CovidRS. Conclusions A risk score using six variables is able to prognosticate mortality within 40-days of hospitalization for COVID-19. Trial registration Clinicaltrials.gov Identifier: NCT04347993.

The MAF translocations, t(14;16) and t(14;20), are considered as adverse prognostic factors based on few studies with small sample sizes. We report on their prognostic impact in a large group of 254 patients - 223 (87.8%) with t(14;16) and 31 (12.2%) with t(14;20). There were no intergroup differences in survival estimates. Median progression-free survival was 16.6 months for t(14;16) and 24.9 months for t(14;20) (p = 0.28). Median overall survival (OS) was 54.0 months and 49.0 months, respectively (p = 0.62). Median OS in patients who underwent double autologous stem cell transplantation (ASCT) was 107.0 months versus 60.0 months in patients who received single ASCT (p < 0.001). ISS 3 was associated with shorter OS (HR = 1.89; 95% CI 1.24-3.19; p = 0.005) in Cox analysis. Our study suggests that t(14;20) should be considered as an adverse factor of equal prognostic implication to t(14;16).

BackgroundTocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19.MethodsWe did a retrospective observational cohort study at 13 hospitals within the Hackensack Meridian Health network (NJ, USA). We included patients (aged ≥18 years) with laboratory-confirmed COVID-19 who needed support in the ICU. We obtained data from a prospective observational database and compared outcomes in patients who received tocilizumab with those who did not. We applied a multivariable Cox model with propensity score matching to reduce confounding effects. The primary endpoint was hospital-related mortality. The prospective observational database is registered on ClinicalTrials.gov, NCT04347993.FindingsBetween March 1 and April 22, 2020, 764 patients with COVID-19 required support in the ICU, of whom 210 (27%) received tocilizumab. Factors associated with receiving tocilizumab were patients' age, gender, renal function, and treatment location. 630 patients were included in the propensity score-matched population, of whom 210 received tocilizumab and 420 did not receive tocilizumab. 358 (57%) of 630 patients died, 102 (49%) who received tocilizumab and 256 (61%) who did not receive tocilizumab. Overall median survival from time of admission was not reached (95% CI 23 days–not reached) among patients receiving tocilizumab and was 19 days (16–26) for those who did not receive tocilizumab (hazard ratio [HR] 0·71, 95% CI 0·56–0·89; p=0·0027). In the primary multivariable Cox regression analysis with propensity matching, an association was noted between receiving tocilizumab and decreased hospital-related mortality (HR 0·64, 95% CI 0·47–0·87; p=0·0040). Similar associations with tocilizumab were noted among subgroups requiring mechanical ventilatory support and with baseline C-reactive protein of 15 mg/dL or higher.InterpretationIn this observational study, patients with COVID-19 requiring ICU support who received tocilizumab had reduced mortality. Results of ongoing randomised controlled trials are awaited.FundingNone.

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.