bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized phase II study of sorafenib with or without everolimus in patients with radioactive iodine refractory Hürthle cell thyroid cancer (HCC) (Alliance A091302/ ITOG 1706).
Authors: Sherman Eric Jeffrey , Foster Nathan R. , Su Yungpo Bernard , Shergill Ardaman , Ho Alan Loh , Konda Bhavana , Ghossein Ronald A , Ganly Ian , Schwartz Gary K.
Published: June 2021

6076

Background: HCC is a rare subtype of follicular cell thyroid cancer that has been poorly studied in the past. Recent genomic studies have shown the PI3K/Akt/mTOR pathway is frequently altered in HCC. In addition, a phase II study of sorafenib (S) and everolimus (E) showed promising data in HCC. A study to evaluate this was initiated through Alliance and the International Thyroid Oncology Group. Methods: Patients (pts) were randomized to either sorafenib and everolimus (SE) vs. sorafenib alone (S). Inclusion criteria included; (1) diagnosis of HCC (confirmed through central review), no prior S or E, refractory to radioactive iodine, progressive disease by RECIST over prior 14 months. Primary endpoint was a comparison of progression-free survival (PFS) between SE and S using a stratified 1-sided log-rank test with 0.20 significance level and a power of 80%. 28 events were needed at final analysis. Secondary endpoints consisted of overall survival (OS), confirmed response rate (RR), and adverse events. Results: 35 pts were randomized from 10/2014 to 9/2019, 34 of which were evaluable for analysis (17-SE; 17-S) because 1 patient cancelled prior to receiving treatment. Median age was 66.5 years and 74% were male. ECOG performance status (PS) was 0 (47%) and PS 1 (53%). 41% had prior systemic treatment for HCC. No significant differences in baseline characteristics were observed between treatment arms. Median follow-up in 22 alive patients was 39.2 months (range: 15.1-64.9). Seven (21%) patients remain on treatment. PFS was significantly improved in the SE arm as compared to the S arm (HR=0.65 (95% CI: 0.26, 1.57); median PFS: SE=24.7 months (95% CI: 6.1-no upper), S=10.9 months (95% CI: 5.5-no upper); stratified 1-sided p=0.1662). OS was similar between the arms (2-sided p=0.4138). Confirmed response rate was similar between arms as well (SE: 18% (3 partial response (PR) vs. S: 24% (3 PR, 1 complete response)); Fisher’s exact p=1.00). Grade 3 adverse event (AE) rates (regardless of attribution) were similar between arms (SE: 77% vs. S: 77%; p=1.00). Each arm had 1 patient with at least one grade 4 AE (SE patient: cardiac arrest, tracheal obstruction, encephalopathy; S patient: mucositis oral) and no grade 5 AEs. Conclusions: PFS was improved with the addition of E to S in this small randomized multi-institutional phase II study done. Accrual was difficult, but these promising results suggest that this combination should be further studied. Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org ; Novartis/GSK; ClinicalTrials.gov Identifier: NCT02143726. Clinical trial information: NCT02143726.
Benefits of pembrolizumab in progressive radioactive iodine refractory thyroid cancer: Results of the AcSé Pembrolizumab Study from Unicancer.
Authors: Leboulleux Sophie , Godbert Yann , Penel Nicolas , Hescot Segolene , De La Fouchardiere Christelle , Blonski Marie , Lamartina Livia , Cousin Sophie , Do Cao Christine , Hadoux Julien , Simon Clotilde , Hoog Labouret Natalie , Chevret Sylvie , Massard Christophe
Published: June 2021

6082

Background: AcSé Pembrolizumab is a Phase II, non-randomized parallel arm, open-label, multicentric study from Unicancer investigating the efficacy and safety of pembrolizumab monotherapy in different cohorts of patients with rare cancers (NCT03012620). Here we report the first results of pembrolizumab in the radioactive iodine refractory thyroid cancer cohort. Methods: Main inclusion criteria were progressive radioactive iodine refractory (RAIR) thyroid cancer (TC) resistant to standard treatment, age > 18, ECOG PS≤1. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycle for a maximum of 2 years. The primary endpoint was the confirmed objective response (OR) rate according to RECIST v1.1 by investigator. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. Results: 43 patients (21 female, mean age 64.8 years; range 40-86) with TC (27 patients with differentiated TC (DTC) [papillary: 7; follicular: 14: oncocytic: 5 poorly differentiated: 1] and 16 patients with anaplastic TC (ATC)) were included from September 2017 to December 2020. The median number of previous systemic treatment lines was 2 (range, 0-7) in DTC and 2.5 (range, 1-4) in ATC. The median number of pembrolizumab cycles was 4 (range, 1-35). The median follow-up was 5.9 months (range: 22 days-22.9 months) for DTC and 2.7 months (range: 3 days- 24.4 months) for anaplastic TC. For DTC the best tumor response was partial response (PR) in 3 (11.1%) patients and stable disease (SD) in 5 (18.5%). Median duration of response was 2.5 months (range: 5 days-7.2 months). The median PFS was 2.6 months, the 6-month PFS was 16.9 %. The median OS was 12.7 months with a 6-month OS of 73.3%. For ATC the best tumor response was PR in 3 cases (18.8 %) and SD in 1 case (6.2 %). Median duration of response was 1.6 months (range: 2 days-7.2 months). The median PFS was 2.3 months, the 6-month PFS was 33.8 %. The median OS was 3.6 months with a 6-month OS of 32.9%. Treatment emergent adverse event included 9 Grade 1-2, 20 Grade 3 (3 being considered as related and 17 as not related) and 1 Grade 4 (sepsis, unrelated). Overall, the toxicity profile was similar to that observed in other cancers. Conclusions: The response rates observed under pembrolizumab is low in DTC and not negligible in ATC, but with a short duration of response. Clinical trial information: NCT03012620.
Medicaid patients more likely to die at home without hospice during the pandemic versus before, exacerbating disparities with commercially insured patients.
Authors: Panattoni Laura Elizabeth , Li Li , Sun Qin , Fedorenko Catherine R. , Sanchez Hayley , Kreizenbeck Karma L. , Shankaran Veena , Ramsey Scott David
Published: June 2021

6502

Background: The COVID-19 pandemic dramatically reduced family access to hospitals and created new barriers to home hospice care, raising concerns about how the pandemic has impacted cancer patients’ place of death and end of life home hospice support. Hypothesizing that Medicaid-enrolled cancer patients may be at greater risk of disruptions in end-of-life care compared to commercially insured patients, we examined changes in place of death and home hospice support for Medicaid and Commercial enrollees following the pandemic. Methods: We linked WA State cancer registry records with claims from Medicaid and approximately 75% of commercially insured cancer patients in the state. Patients ages 18-64 with solid-tumor malignancies who died March-June 2020 (COVID) were compared to those who died March-June 2017-2019 (Pre-COVID). Place of death was categorized as hospital, home with hospice, and home without hospice; nursing home deaths were excluded. Given our sample size, we examined differences in the likelihood of place of death with Fisher’s exact tests and multinomial logistic regressions stratified by payer and by COVID period, controlling for age, gender, race, stage, cancer type, and census tract-level neighborhood deprivation. We report marginal effects. Results: In Fisher’s exact analyses, Medicaid but not commercial patients were significantly less like to die in hospital and more likely to die at home without hospice during COVID (Table). In pre-post adjusted analysis of Medicaid patients, the probability of dying in the hospital was 12.3% (p=0.03) percentage points lower during the pandemic versus before, while the probability of dying at home without hospice was 11.1% (p=0.04) greater. Place of death did not change significantly pre-post for commercial patients. In addition, Pre-COVID, the probability of dying in the hospital was 10.7% (p=0.03) greater for Medicaid than commercial patients. During COVID, the probability of dying at home without hospice was 15.8% (p=0.04) greater for Medicaid versus commercial patients but lower for women (ME=20.2%; p=0.01) and colorectal versus breast cancer patients (ME=39.2%; p=0.01). Conclusions: Following COVID, Medicaid patients place of death shifted from hospital to homes, but without an increase in the use of home hospice services. In contrast, place of death and hospice use among commercial patients did not significantly change. This widening disparity in home deaths without hospice services raises concerns that the pandemic disproportionately worsened end of life experience for low income patients with cancer.[Table: see text]
Association between perceptions of prognosis and end-of-life outcomes for patients with advanced lung and gastrointestinal cancer.
Authors: Topping Carlisle E. W. , Elyze Madeleine , Plotke Rachel , Heuer Lauren , Vyas Charu , Greer Joseph A. , Nipp Ryan David , Temel Jennifer S. , El-Jawahri Areej
Published: June 2021

6503

Background: Many patients with advanced cancer maintain misperceptions of their prognosis and are thus unprepared to make difficult decisions regarding their end-of-life (EOL) care. However, studies examining the associations between patients’ perceptions of their prognosis and their EOL outcomes are limited. Methods: We conducted a secondary analysis using longitudinal data from a randomized controlled trial of a palliative care intervention for patients with newly diagnosed incurable lung and non-colorectal gastrointestinal cancer. We administered the Prognosis and Treatment Perceptions Questionnaire to assess patients’ perceptions of their prognosis at baseline, week-12, and week-24, using the final assessment closest to death. We used multivariate logistic and linear regression models, adjusting for age, gender, marital status, cancer type, and randomization to the palliative care intervention, to examine the associations among patients’ perceptions of their prognosis with the following EOL care outcomes abstracted from the electronic health record: 1) hospice utilization and length-of-stay (LOS); 2) hospitalizations in the last 30 days of life; 3) receipt of chemotherapy in the last 30 days of life; and 4) location of death. Results: We enrolled 350 patients in the parent trial, of which 80.5% (281/350) died during the study period and were included in this analysis. Overall, 59.4% (164/276) of patients reported that they were terminally ill, and 66.1% (154/233) reported that their cancer was likely curable at the assessment closest to death. In multivariate analyses, patients who reported that their cancer was likely curable were less likely to utilize hospice (OR = 0.25, 95%CI 0.10-0.61, P = 0.002) or die at home (OR = 0.56, 95%CI 0.32-0.98, P = 0.043), and more likely to be hospitalized in the last 30 days of life (OR = 2.28, 95%CI 1.20-4.32, P = 0.011). In contrast, patients’ report that they were terminally ill was only associated with lower likelihood of hospitalizations in the last 30 days of life (OR = 0.52, 95%CI 0.29-0.92, P = 0.025). Patients’ perceptions of their prognosis were not associated with hospice LOS or chemotherapy administration in the last 30 days of life. Conclusions: Patients’ perceptions of their prognosis are associated with important EOL outcomes including hospice utilization, hospitalizations at the EOL, and death at home. Interventions are needed to enhance patients’ perceptions of their prognosis in order to optimize their EOL care.
Racial and ethnic enrollment disparities in acute myeloid leukemia clinical trials.
Authors: Hantel Andrew , DeAngelo Daniel J. , Luskin Marlise Rachael , Garcia Jacqueline Suen , Abel Gregory A.
Published: June 2021

6523

Background: Racial and ethnic disparities in clinical trial enrollment compound inequities in drug development and the delivery of patient-centered care. Despite significant survival disparities in acute myeloid leukemia (AML), enrollment disparities data are limited. Methods: We performed a structured search and abstraction of demographic data for all United States (US) AML clinical trials from 2002-2017 listed on clinicaltrials.gov and compared the results to the incidence and demographic distribution of AML using the Surveillance, Epidemiology, and End Results program and 2010 US Census. We calculated enrollment fractions (the number of enrollees divided by the number of incident cases) for the five mutually exclusive race/ethnicity groups of non-Hispanic White (NH-White), Black (NH-Black), Asian/Pacific Islander (NH-Asian/PI), American Indian/Native Alaskan (NH-AI/AN), and Hispanic patients. We compared these using X2 testing, with NH-White as the comparator, and reported odds ratios with 95% confidence intervals (CI). To assess trends over time, we adjusted enrollment from 2005-2008 for changes in AML incidence and NH-White enrollment for a later period (2011-2014), comparing this expected enrollment fraction to the actual enrollment fraction during that later period. Results: Of 223 eligible studies (patient N=17372) on clinicaltrials.gov, 99 (44.4%) reported racial demographics (N=8417; 48.5%) and 68 (30.5%) reported race and ethnicity (N=6554; 37.7%). Enrollment and incidence proportions by race are shown in the table. Among trials reporting race and ethnicity, all groups had lower odds of enrollment compared to NH-White patients (Table). For the 99 trials reporting race data, Black and AI/AN patient enrollment odds were lower (OR 0.60 [95% CI: 0.55, 0.65]; 0.50 [95% CI: 0.33, 0.76]), but Asian/PI enrollment was not (OR 0.91 [95% CI: 0.82, 1.01]). The relative enrollment of NH-Black, NH-Asian/PI, and Hispanic patients declined later in the study period (Table). Conclusions: In AML clinical trials performed in the US from 2002-2017, NH-White patients were enrolled at higher rates compared to other racial and ethnic groups; enrollment diversity declined over time. An important first step to reducing enrollment disparities will be to improve the reporting of demographic enrollment data.[Table: see text]
Access to cancer care for Medicaid patients at cancer hospitals in the United States.
Authors: Marks Victoria A. , Hsiang Walter R. , Nie James , Buck Matthew , Demkowicz Patrick C , Umer Waez , Haleem Afash , Galal Bayan , Pak Irene , Kim Dana , Kenney Patrick Aloysius , Leapman Michael S.
Published: June 2021

6548

Background: As the result of expansions associated with the Affordable Care Act (ACA), one in five Americans are now insured through Medicaid. Despite overall increases, access to care for Medicaid-insured patients with cancer may be limited by facilities due to lower reimbursement and administrative burden. We aimed to directly assess facility-level acceptance of Medicaid patients with a new diagnosis of cancer. Methods: We performed a cross-sectional secret shopper study to evaluate access to cancer care for colorectal, breast, urologic, and skin cancer at Commission on Cancer (CoC) accredited hospitals. We studied the relationship between Medicaid access and facility-level characteristics assessed through American Hospital Association and Center for Medicare and Medicaid Service data using univariable statistics and multivariable logistic regression. Results: Among 334 CoC facilities contacted, the overall rate of Medicaid acceptance for at least one investigated cancer type was 99% (n = 331). However, we identified hospital-level variation in Medicaid acceptance across cancer types, where Medicaid acceptance for colorectal, breast, urologic, and skin cancer was 90%, 96%, 87%, and 80%, respectively. Of the hospitals that accepted Medicaid, 2% accepted Medicaid for one cancer type, 8% for two, 21% for three, and 68% for all four cancer types. In multivariable logistic regression, odds of Medicaid acceptance were lowest in comprehensive community cancer centers (p < 0.05 for colorectal and urologic cancer) and for-profit designated facilities (p < 0.05 for urologic and skin cancer) (Table). Hospitals in states with Medicaid expansion were also more likely to accept Medicaid for urologic (OR: 2.5, 95% CI: 1.2-5.2) and breast (OR: 12.8, 95% CI: 2.7-60.2) cancer care. Conclusions: Access disparities persist for patients with Medicaid, with acceptance rates differing substantially within and between facilities. Facility-level differences in Medicaid access among CoC facilities are notable given the use of hospital registry data to estimate ACA-related effects.[Table: see text]
Racial disparities in access to prostate cancer clinical trials: A county-level analysis.
Authors: Bansal Aasthaa , Wang Wei-Jhih , Bennette Caroline Savage , Ramsey Scott David
Published: June 2021

6553

Background: African American men (AAs) have a higher burden of prostate cancer compared to other populations. We sought to determine if they experience disparities in access to prostate cancer clinical trials. Methods: We created a county-level database of all U.S. counties by linking together prostate cancer clinical trial data from the Aggregate Analysis of ClincalTrials.gov (AACT) database with county-level socioeconomic, demographic and healthcare facility data derived from several external data sources. Using this data linkage, we examined two specific potential access barriers. First, we investigated the relationship between %AAs in the county and access to NCI designated cancer facilities, adjusting for county population size and other characteristics. Then, among counties with cancer facilities, we investigated the relationship between the %AAs in the county and number of available prostate cancer treatment trials per capita per year. We used logistic and negative binomial regression models, respectively, to address these questions. Results: Between 2008 and 2015, 613 prostate cancer trial sites were found among 3,145 U.S. counties. Counties with higher %AAs were less likely to have cancer facilities (adjusted odds ratio = 0.85, 95% CI (0.78, 0.92)). Among counties with cancer facilities, those with higher %AAs had significantly fewer prostate cancer trials per capita per year (rate ratio per 10% increase in %AAs: 0.90, 95% CI (0.83,0.96)), after adjusting for county-level sociodemographic and healthcare system factors. Conclusions: Counties with higher proportions of AAs appear to be less likely to have access to NCI designated cancer facilities. Among counties with cancer facilities, those with higher proportions of AAs appear to have fewer available prostate cancer treatment trials per capita per year. Clinical trials in prostate cancer therapy should ensure adequate availability of enrollment sites in regions with high concentrations of AAs.
The impact of HIV infection on overall survival among women with stage IV breast cancer in South Africa.
Authors: Pumpalova Yoanna S , Ayeni Oluwatosin , Chen Wenlong Carl , O'Neil Daniel , Nietz Sarah , Phakathi Boitumelo , Buccimazza Ines , Cacala Sharon , Stopforth Laura , Farrow Hayley , Joffe Maureen , Mapanga Witness , Jacobson Judith , Crew Katherine D. , Cubasch Herbert , Ruff Paul , Neugut Alfred I.
Published: June 2021

6559

Background: Advanced stage at breast cancer (BC) diagnosis is common in sub-Saharan Africa. In public hospitals across South Africa (SA), 10-15% of women present with metastatic BC, compared to <5% in the U.S., and 20% of new BCs are diagnosed in women living with HIV (WLWH). We evaluated the impact of HIV on overall survival (OS) among women with stage IV BC, which is associated with a poor prognosis in SA. Methods: We conducted a prospective cohort study of women diagnosed with stage IV BC between February 2, 2015 and September 18, 2019 at six public hospitals in SA. Baseline characteristics were compared by HIV status and multivariate Cox regression models were used to estimate the effect of HIV on OS. Results: Among 550 eligible women, 147 (26.7%) were WLWH. Compared to HIV-negative BC patients, WLWH were younger (median age 45 vs. 60 years, p<0.001), predominantly black (95.9% vs. 77.9%, p<0.001), and more likely to have hormone receptor-negative BC (32.7% vs. 22.6%, p=0.016). HER2 tumor status did not differ by HIV status (25.3% HER2 positive overall), and Ki67 index was not increased among WLWH (57.1% Ki67 > 20 overall). Receipt of systemic anti-cancer therapy did not differ by HIV status (80.9% treated overall) and most women were treated with anthracycline (55.5%). HIV status was not associated with OS (Hazard Ratio (HR)=1.13, 95% confidence interval (CI)=0.89-1.44) (Table). In an exploratory subgroup analysis, WLWH and hormone receptor-negative BC had shorter OS compared to HIV-negative women (1-year OS: 27.1% vs. 48.8%, p=0.003; HR=1.94, 95% CI=1.27-2.94), which was not observed for hormone receptor-positive BC. Results were unchanged when analysis was restricted to black women only. Conclusions: HIV status was not associated with worse OS in women with stage IV BC in SA and cannot account for the poor survival in our cohort. Subgroup analysis revealed that WLWH with hormone receptor-negative BC had worse OS; this differential effect of HIV on BC survival by hormone receptor status is a novel finding that warrants further investigation.[Table: see text]
Impact of disruptions in breast cancer control due to the COVID-19 pandemic on breast cancer mortality in the United States: Estimates from collaborative simulation modeling.
Authors: Alagoz Oguzhan , Lowry Kathryn P. , Kurian Allison W. , Mandelblatt Jeanne S. , Ergun Mehmet Ali , Huang Hui , Lee Sandra J. , Schecter Clyde , Tosteson Anna N.A. , Miglioretti Diana L. , Trentham-Dietz Amy , Nyante Sarah , Kerlikowske Karla , Sprague Brian L. , Stout Natasha K.
Published: June 2021

6562

Background: The COVID-19 pandemic has disrupted breast cancer control through short-term declines in screening, delays in diagnosis and reduced/delayed treatments. We projected the impact of COVID-19 on future breast cancer mortality.Methods: Three established Cancer Intervention and Surveillance Modeling Network (CISNET) models projected the impact of pandemic-related care disruptions on breast cancer mortality between 2020 and 2030 vs. pre-pandemic care patterns. Based on Breast Cancer Surveillance Consortium data, we modeled reductions in mammography screening utilization, delays in symptomatic cancer diagnosis, and reduced use of chemotherapy for women with early-stage disease for the first six months of the pandemic with return to pre-pandemic patterns after that time. Sensitivity analyses were performed to determine the effect of key model parameters, including the duration of the pandemic impact. Results: By 2030, the models project 1,297 (model range: 1,054-1,900) cumulative excess deaths related to reduced screening; 1,325 (range: 266-2,628) deaths from delayed diagnosis of symptomatic women, and 207 (range: 146-301) deaths from reduced chemotherapy use for early-stage cancer. Overall, the models predict 2,487 (range 1,713-4,875) excess deaths, representing a 0.56% (range: 0.36%-0.99%) cumulative increase over deaths that would be expected by 2030 in the absence of the pandemic’s disruptions. Sensitivity analyses indicated that the impact on mortality would approximately double if the disruptions lasted for a 12-month period. Conclusions: The impact of the initial pandemic-related disruptions in breast cancer care will have a small long-term cumulative impact on breast cancer mortality. The impact of the initial pandemic-related disruptions on breast cancer mortality will largely be mitigated by the rapid return to usual care. As the pandemic continues it will be important to monitor trends in care and reassess the mortality impact.[Table: see text]
Initial reporting from the prospective National Cancer Institute (NCI) COVID-19 in Cancer Patients Study (NCCAPS).
Authors: Korde Larissa A. , Best Ana F. , Gnjatic Sacha , Denicoff Andrea M. , Mishkin Grace E. , Bowman Melissa , Harris Lyndsay , Geiger Ann M. , McCaskill-Stevens Worta J. , Chanock Stephen J. , Spears Patricia , Rubinstein Lawrence , Mark Nicholas M. , Warner Jeremy Lyle , Allegra Carmen Joseph , Esbenshade Adam J. , Knopp Michael V. , Doroshow James H. , Rini Brian I. ,   NCCAPS Study Team
Published: June 2021

6565

Background: Patients (pts) with cancer are at increased risk of SARS-CoV-2 infection and severe COVID-19 disease. Longitudinal follow-up is needed to characterize the severity, sequelae and outcomes in pts with cancer who develop COVID-19. Methods: NCCAPS is a prospective, longitudinal study (NCT04387656) aiming to accrue 2,000 pts with cancer undergoing active treatment or prior stem cell transplant for hematologic or solid tumor malignancy. Adult patients are eligible to enroll within 14 days of their first positive SARS-CoV-2 test; pediatric patients may also enroll retrospectively. Clinical data, patient-reported outcomes, blood specimens, and imaging are collected for up to 2 years. This abstract provides initial baseline and 2-month follow-up data. Results: As of Jan 22, 2021, 585 pts (552 adults and 33 pediatric pts) had complete baseline data and of these pts, 215 adults had 2 months of complete follow-up data. 23.4% of adults and 42.4% of pediatric pts were of non-White race and/or Hispanic/Latinx ethnicity. The most common cancer diagnoses were breast (19.6%), lung (9.9%) and multiple myeloma (8.9%) in adults and acute leukemia (AML/ALL; 63.6%) in children. The most recent treatment was chemotherapy in 38.2%, immunotherapy in 9.6%, and radiation in 5.4%. Median time from positive SARS-CoV-2 test to study enrollment was 10.5 days in adults and 18 days in pediatric pts. Preliminary analysis of plasma cytokines will be presented. At enrollment, 84.6% of adults had COVID-19 symptoms. 55.9% reported symptoms 2 weeks after their positive SARS-CoV-2 test; this fell to 39.0% at 1 month and 28.8% at 2 months (see Table). Of the 215 adults with complete data at 2 months, sequelae included pulmonary (n=22, 10%), cardiovascular (n=12, 6%) thromboembolic (n=9, 4%), bleeding (n=9, 4%) and gastrointestinal (n=11, 5%). 144 (67%) reported at least one cancer treatment disruption in the first 2 months, most commonly delayed therapy (n=98; 46%).Of the 348 adults with baseline data and SARS-CoV-2 test date prior to Nov 23, 2020, 6.3% had died (median time from SARS-CoV-2 test to death: 27 days), and 22.1% reported at least one hospitalization for COVID-19. No deaths were reported in the pediatric population. Conclusion: Cancer pts with COVID-19 report ongoing symptoms after acute infection and a substantial number develop sequelae. Cancer treatment disruptions are common in the initial months following SARS-CoV-2 infection. Longer follow-up will inform whether these treatment disruptions are associated with adverse outcomes. Clinical trial information: NCT04387656. [Table: see text]
Initial report on hospitalized cancer patients with COVID-19 from the National Cancer Institute (NCI) COVID-19 in Cancer Patients Study (NCCAPS).
Authors: Mark Nicholas M. , Best Ana F. , Khorana Alok A. , Pergam Steven , Mishkin Grace E. , Bowman Melissa , Denicoff Andrea M. , Rubinstein Lawrence , Shankar Lalitha Krishna , Doroshow James H. , Rini Brian I. , Korde Larissa A. ,   NCCAPS Study Team
Published: June 2021

6566

Background: Hospitalized cancer patients (pts) with COVID-19 have a severe disease course and high mortality. Pts with lung cancer, hematologic malignancies and metastatic disease may be at higher risk. Detailed prospective inpatient data may help to identify those at greatest risk for poor outcomes. Methods: NCCAPS is a longitudinal study aiming to accrue 2,000 cancer pts undergoing treatment for hematologic malignancy or solid tumor with COVID-19. For pts’ first COVID-19 hospitalization, clinical data, research blood specimens and imaging are collected, and additional clinical data are collected during subsequent hospitalizations. Results: As of Jan. 22, 2021, among 757 enrolled adult patients from 204 sites, 124 (16.3%) reported at least one hospitalization for COVID-19, and discharge data was available for 98 hospitalizations in 88 patients. The median age was 67 (range 21-93, 1Q:56, 3Q:72), 35/88 (40%) were female. The most common malignancies in hospitalized adult pts were lymphoma (18.2%), lung cancer (15.9%) and multiple myeloma (10.2%). The most common presenting symptoms were shortness of breath (65%), fatigue/malaise (64%), and fever (49%). 8/88 (9%) pts were neutropenic (ANC < 1000) at presentation; 17/88 (19%) were thrombocytopenic. Median length of stay was 6.5 days (range 1-41, 1Q:4, 3Q:12). Among those hospitalized, 20/88 (22.7%) received care in the ICU or high dependency unit, with a median ICU stay of 7 days (range 1-22, 1Q:2.5, 3Q:9.5); of those admitted to the ICU, 25% (5/20) received invasive mechanical ventilation. Of those in whom inpatient medications were recorded (n = 63), 63% received corticosteroids, 46% received remdesivir, and 14% received convalescent plasma. One pt received bamlanivimab and 2 patients received tocilizumab. Most (46/63; 73%) received anticoagulation, primarily prophylactic low molecular weight heparin; 11/63 (17%) received therapeutic dose anticoagulation. Inpatient D-dimer values were recorded in 43 inpatients, 26 of whom had multiple measurements. 16/98 hospitalizations ended with death (16%). Conclusions: Preliminary analysis of NCCAPS data reveals that inpatient hospital admission is common among oncology patients with COVID-19 and mortality rates appear high within this cohort. Hematologic malignancies and lung cancer are the most common underlying diagnoses in patients requiring hospitalization. Corticosteroids and anti-coagulation were the most commonly used therapies. Despite high rates of ICU admission, invasive mechanical ventilation may be instituted less often in an oncology cohort. These observations may inform decisions about vaccine policy and decisions to limit life sustaining treatment. Clinical trial information: NCT04387656.
Knowledge about risks, benefits, and curative potential of immunotherapy among patients with advanced lung cancer or melanoma.
Authors: Petrillo Laura A , Zhou Ashley , Sullivan Ryan J. , Volandes Angelo E. , Greer Joseph A. , Temel Jennifer S. , El-Jawahri Areej
Published: June 2021

6579

Background: Immunotherapy is a novel treatment paradigm that has improved survival for patients with advanced melanoma and lung cancer and poses new risks of immune-related adverse events, which are important for patients to recognize promptly. We aimed to describe patients’ knowledge about the risks and benefits of immunotherapy, and their understanding of the goal of treatment with immunotherapy. Methods: We conducted a cross-sectional study of patients at a single institution who had initiated therapy with an immune checkpoint inhibitor for advanced melanoma, small cell lung cancer, or non-small cell lung cancer in the past 12 weeks. We assessed patients’ knowledge about immunotherapy with a 9-item knowledge questionnaire (score range 0-100; higher score represents greater knowledge). We used the Perception of Treatment and Prognosis Questionnaire to assess patients’ understanding of the goal of their treatment. We used the two-sample t-test to compare knowledge scores and chi-square test to compare goals of therapy between patients with melanoma and lung cancer. Results: A total of 105 patients (57 with melanoma, 48 with lung cancer) completed the study questionnaire. Participants had a median age of 69 years (range 36-89), and 33% (35/105) were female. Participants’ mean knowledge score was 69.0 (SD = 23.3). Overall, 91% (96/105) of patients endorsed that immunotherapy works by turning on the body’s immune system to recognize and attack cancer cells and 33% (35/105) correctly identified that immunotherapy does not kill all rapidly dividing cells. With respect to immunotherapy side effects, 68% (71/105) of patients reported that immunotherapy side effects can affect any organ in the body and 65% (68/105) endorsed that side effects from immunotherapy can occur at any time, even after the treatment ends. Overall, 34% (36/105) of participants reported that the primary goal of their treatment is to cure their cancer. Participants with melanoma had higher mean knowledge scores compared to those with lung cancer (74.7 vs. 62.3, P = 0.003). Participants with melanoma were also more likely to report that the goal of their immunotherapy was to cure compared to those with lung cancer (58% [33/57] vs. 6% [3/48], P < 0.001) and that their oncologist had said that immunotherapy would cure their cancer (19% [11/57] vs. 0% [0/48], p = 0.005). Conclusions: We observed substantial knowledge deficits about immunotherapy and perceptions that immunotherapy is a cure for advanced cancer, particularly among patients with melanoma. These findings underscore the need for interventions to enhance patients’ knowledge about immunotherapy and to help them understand the goal of immunotherapy for patients with advanced cancer.
Phase II study of the IDH2-inhibitor enasidenib in patients with high-risk IDH2-mutated myelodysplastic syndromes (MDS).
Authors: Venugopal Sangeetha , Dinardo Courtney Denton , Takahashi Koichi , Konopleva Marina , Loghavi Sanam , Borthakur Gautam , Dezern Amy Elizabeth , Masarova Lucia , Daver Naval Guastad , Short Nicholas James , Alvarado Yesid , Ravandi Farhad , Montalban-Bravo Guillermo , Sasaki Koji , Delumpa Ricardo , Sekeres Mikkael A. , Patel Bhumika J , Roboz Gail J. , Kantarjian Hagop M. , Garcia-Manero Guillermo
Published: June 2021

7010

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. Clinical trial information: NCT03383575. [Table: see text]
Contemporary outcomes for adults with AML requiring ICU admission.
Authors: Hammond Danielle , Sasaki Koji , Geppner Alexis , Haddad Fadi , Mohamed Shehab , Rivera Daniel , Siddiqui Maria , Alwash Yasmin , Ramos Perez Jorge , Morita Kiyomi , Kim Kunhwa , Pierce Sherry , Gutierrez Cristina , Pemmaraju Naveen , Borthakur Gautam , Dinardo Courtney Denton , Ravandi Farhad , Garcia-Manero Guillermo , Kantarjian Hagop M. , Kadia Tapan M.
Published: June 2021

7025

Background: Patients (pts) with AML frequently encounter life-threatening complications requiring transfer to an intensive care unit (ICU). Methods: Retrospective analysis of 145 adults with AML requiring ICU admission at our tertiary cancer center 2018-19. Use of life-sustaining therapies (LSTs) and overall survival (OS) were reported using descriptive statistics. Logistic regression was used to identify risk factors for in-hospital death. Results: Median age was 64 yrs (range 18-86). 47% of pts had an ECOG status of ≥ 2 with a median of at least 1 comorbidity (Table). 117 pts (81%) had active leukemia at admission. 68 pts (47%) had poor-risk cytogenetics (CG) and 32 (22%) had TP53-mutated disease. 61 (42%), 27 (19%) and 57 pts (39%) were receiving 1st, 2nd and ≥ 3rd line therapy. 33 (23%) and 70 pts (48%) were receiving intensive and lower-intensity chemotherapy, respectively, and 77 pts (53%) were concurrently on venetoclax. Most common indications for admission were sepsis (32%), respiratory failure (24%) and leukocytosis (12%); Table outlines additional ICU admission details. Median OS from the date of ICU admission was 2.0 months (mo) for the entire cohort and 6.9, 1.6 and 1.2 mo in pts with favorable-, intermediate- and poor-risk CG. Median OS of pts receiving frontline vs. ≥ 2nd line therapy was 4.2 vs. 1.4 mo (P<0.001). Median OS in pts requiring 0-1 vs. 2-3 LSTs was 4.1 vs. 0.4 mo (P<0.001). OS was not different by age, co-morbidity burden nor therapy intensity. In a multivariate analysis that included SOFA scores, only adverse CG (OR 0.35, P = 0.028), and need for intubation with mechanical ventilation (IMV; OR 0.19, P = 0.009) were associated with increased odds of in-hospital mortality. Conclusions: A substantial portion of pts with AML survive their ICU admission with sufficient functionality to return home and receive subsequent therapy. In contrast to general medical populations, age, co-morbidities, and SOFA scores were not independently predictive of in-hospital mortality. Disease CG risk and the need for IMV were the strongest predictors of ICU survival. This suggests that many pts with AML can benefit from ICU care.[Table: see text]
Subcutaneous epcoritamab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma: Safety profile and antitumor activity.
Authors: Clausen Michael Roost , Lugtenburg Pieternella , Hutchings Martin , Johnson Peter W. M. , Linton Kim M. , Lewis David John , Chamuleau Martine , Sureda Balari Anna , Cunningham David , Elliott Brian , DeMarco Dena , Chen Kuo-mei , Mous Rogier
Published: June 2021

7518

Background: Epcoritamab is a CD20xCD3 bispecific antibody that induces T-cellmediated killing of CD20–positive malignant B-cells. We present updated data, including progression-free survival (PFS) from the dose escalation part of the first-in-human phase 1/2 study of epcoritamab in pts with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL; NCT03625037). Methods: Adults with R/R CD20+ B-NHL received flat-dose 1 mL SC epcoritamab (step-up dosing approach) in 28-day cycles (q1w: cycles 1–2; q2w: cycles 3–6; q4w thereafter) until disease progression or unacceptable toxicity. Step-up dosing and standard prophylaxis were used to mitigate severity of cytokine release syndrome (CRS). Results: At data cut off (1/31/2021), 68 pts with B-NHL were enrolled across histologies including diffuse large B-cell lymphoma (DLBCL; n = 46 [67.6%]; de novo and transformed), follicular lymphoma (FL; 12 [17.6%]), mantle cell lymphoma (MCL; 4 [5.9%]), and others (6 [8.8%]). Majority were heavily pretreated (median [range] prior lines: DLBCL, 3 [1–6]; FL, 4.5 [1–18]); including prior CAR-T (n = 6) and prior ASCT (n = 10). At median follow-up of 14.1 mo (DLBCL, 10.2 mo; FL, 15.2 mo), treatment was ongoing in 15 (22%) pts. Most common treatment-emergent adverse events (AEs) were pyrexia (69%), CRS (59%), and injection site reaction (47%). CRS events were all grade 1 or 2 and most occurred in cycle 1; neurotoxicity was limited (6%; grade 1: 3%; grade 3: 3%; all transient). One case of tumor lysis syndrome was observed (1.5%; grade 3); there were no cases of febrile neutropenia or treatment-related death. Overall response is shown for DLBCL ≥12 mg and ≥48 mg and FL ≥12 mg, corresponding to the minimal efficacy threshold (Table). Responses deepened over time (PR converted to CR: DLBCL, 6 pts; FL, 3 pts). Median time to response was 1.4 mo (DLBCL) and 1.9 mo (FL). Among DLBCL pts achieving CR with ≥6 mg (n = 11), none relapsed while on treatment. The median PFS for pts with DLBCL ≥12 mg (n = 22) was 9.1 mo (95% CI: 1.6, NE; median follow-up 9.3 mo) and for pts with DLBCL ≥48 mg (n = 11) median PFS was not reached (median follow-up 8.8 mo). Updated analyses will be presented. Conclusions: With longer follow-up, SC epcoritamab demonstrated substantial single-agent activity, inducing deep and durable clinically meaningful responses, with a consistent safety profile. Notably no severe (grade ≥3) CRS events, no febrile neutropenia, and limited neurotoxicity was observed. Clinical trial information: NCT03625037. [Table: see text]
CNS relapse in DLBCL patients below 60 years treated with R-ACVBP, R-CHOEP, or R-CHOP: A joint analysis of LYSA and GLA/DSHNHL.
Authors: Thieblemont Catherine , Altmann Bettina , Casasnovas Olivier , Frontzek Fabian , Morschhauser Franck , Oberic Lucie , Poeschel Viola , Fitoussi Olivier , Renaud Loïc , Lenz Georg , Mounier Nicolas , Rosenwald Andreas , Ott German , Molina Thierry , Parrens Marie , Chartier Loic , Ziepert Marita , Tilly Herve , Schmitz Norbert
Published: June 2021

7543

Background: Central nervous system (CNS) relapse occurs in 2-6% of DLBCL patients (pts) increasing to 10% or more in high-risk groups. Intrathecal (IT) or intravenous high-dose methotrexate (HD MTX) have limited if any prophylactic impact on CNS relapse. To address the role of systemic first-line therapy in pts tolerating intensified strategies (R-ACVBP, R-(Mega)CHOEP, R-CHO(E)P), we compared CNS relapses occurring in a large cohort of pts ≤60 years. Methods: We conducted a retrospective analysis including previously untreated pts with DLBCL by central review, age 18-60 years, from multicenter clinical trials conducted by LYSA and GLA/DSHNHL (Table). We assessed the risk of CNS relapse in matched cohorts based on the aaIPI. Results: A total of 2203 pts were included. Median age was 47 years (18-60). 455 pts were treated with R-ACVBP, 444 with R-(Mega)CHOEP, 1304 with R-CHOP. Distribution of CNS IPI was not significantly different comparing R-ACVBP to R-CHO(E)P groups within aaIPI categories (Table). PFS and OS were comparable according to treatment within aaIPI groups, also adjusted for prognostic factors. No CNS events occured during observation time of 3 years in pts with aaIPI 0. In pts with aaIPI 1, no CNS event occured in the R-ACVPB arm, the 3y-cumulative incidence of CNS relapse for pts treated with R-CHO(E)P group was 1.0% (95%CI 0.3-1.7). In pts with aaIPI 2,3 and intermediate/high CNS IPI, four (1.6%) treated with R-ACVBP experienced relapse in the CNS compared to 15 (3.9%) pts treated with R-(Mega)CHO(E)P (3y-cumulative incidence 1.6% (95%CI 0-3.2) vs. 4.0% (95%CI 2.0-6.0). Conclusions: CNS relapse was extremely rare in younger DLBCL pts with aaIPI 0 or 1; prophylactic measures are not warranted. In pts with aaIPI 2,3 (and intermediate/high CNS-IPI), only 4 (1.6%) CNS relapses were seen with the R-ACVBP while 15 (3.9%) relapses did occur after R-(Mega)CHO(E)P. This analysis underlines the important role of the systemic therapy in controling CNS relapse.[Table: see text]
MASS-FIX versus standard methods to predict for PFS and OS among multiple myeloma patients participating on the STAMINA trial.
Authors: Dispenzieri Angela , Krishnan Amrita Y. , Arendt Bonnie , Dasari Surendra , Efebera Yvonne Adeduni , Geller Nancy , Giralt Sergio , Hahn Theresa , Kohlhagen Mindy C. , Landau Heather Jolie , Hari Parameswaran , Pasquini Marcelo C. , Qazilbash Muzaffar H. , McCarthy Philip L. , Shah Nina , Vesole David H. , Vogl Dan T. , Wallace Paul K. , Stadtmauer Edward A. , Murray David L.
Published: June 2021

8009

Background: Measuring response among patients with multiple myeloma is essential for the care of patients. Deeper responses have been associated with better progression free survival (PFS) and overall survival (OS). Serum (SIFE) and urine immunofixation are the currently used markers for biochemical documentation of CR after which marrow is tested for plasma cell clearance. Next generation flow cytometry and sequencing are used to document the presence of minimal residual disease (MRD). Mass spectrometry of blood by MALDI (Mass-Fix) is a new simple, inexpensive, sensitive, and specific means of detecting monoclonal immunoglobulins. To better test the hypothesis that Mass-Fix is superior to existing methodologies to predict for survival outcomes—especially SIFE-- samples from the STAMINA trial (NCT01109004), a trial comparing 3 transplant approaches among patients who have already received induction, were employed. Methods: Five-hundred and seventy-five patients were included. Samples from enrollment post-induction (post-I) and 1-year post enrollment (1YR) were tested when available. Four response parameters were assessed univariately: Mass-Fix, SIFE, complete response, and MRD by next generation flow cytometry. Mass spectrometry spectra were evaluated in a blinded fashion. Complete response was according to the 2006 International Myeloma Working Group criteria. Multivariate Cox proportional hazard models using stepwise regression were developed to explore the independent effect of the different response parameters on PFS and OS and interactions with other risk factors. Results: Of the 4 response measures, only MRD and Mass-Fix predicted for PFS and OS at multiple testing points on multivariate analyses (Table). Of the 4 post-I measurements, only MRD predicted for PFS; however, Mass-Fix was the only post-I measurement to predict for OS. Of all the 1-year measures, both 1YR Mass-Fix and 1YR MRD positivity predicted for inferior PFS and OS. In models including MRD and Mass-Fix, SIFE and CR were not prognostic for PFS or OS. Conclusions: Mass-Fix is a powerful means to track monoclonal proteins. The full utility of Mass-Fix was not exploited given the absence of a diagnostic sample and the fact that only serum (and not urine) was tested. Despite these limitations, it performed well at pre-induction and at 1 year. Mass-Fix provides a convenient and non-invasive means of predicting for myeloma outcomes. Clinical trial information: NCT01109004. [Table: see text]