bluuebunny/crossref_metadata_2025 huggingface dataset:
Financial toxicity in Hispanic cancer survivors: A nationally representative pancancer analysis.
Authors: Swami Nishwant , Dee Edward Christopher , Mahal Brandon A , Chino Fumiko , Duma Narjust
Published: June 2022

6528

Background: A cancer diagnosis can pose a significant financial burden to patients and their families, both during and after treatment. Financial toxicity has long-term consequences, with cancer being the most commonly cited reason for medical cost-associated bankruptcy in the United States. We used nationally representative survey data to assess financial toxicity in cancer survivors, with a focus on Hispanic patients given known disparities in socioeconomic and cancer outcomes. Methods: 2013-2018 data from the National Health Interview Survey (NHIS) was used to select individuals aged 18 years old and older who reported any previous diagnosis of cancer. Financial toxicity was defined as unmet healthcare need, health care unaffordability, and/or general financial stress. Individuals were disaggregated by race/ethnicity, and patients who self-identified as Hispanic were further classified by country of origin. Survey-adjusted percentages characterize the cohort. Multivariable logistic regression generated adjusted odds ratios (aORs) with 95% CI for each category of financial toxicity, with non-Hispanic White (NHW) used as reference. Results: Hispanic patients in aggregate had the highest prevalence of all 3 categories of financial toxicity when compared to other racial/ethnicity groups (35% unmet healthcare need, 61% healthcare unaffordability, 61% financial stress). Mexican (aOR: 2.53 95%CI: 1.82–3.52), Cuban/Cuban-American (aOR: 1.97 95%CI: 1.17–3.34), and patients of Central/South American heritage (aOR: 2.61 95%CI: 1.67–4.10) were more likely to have healthcare unaffordability. Unmet healthcare needs were higher in Mexican patients (aOR: 1.43 95%CI: 1.03-1.99) and patients of Cuban descent (aOR: 1.96 95%CI: 1.07-3.58). Financial stress was highest among patients of Central/South American heritage (aOR: 4.20 95%CI: 2.50-7.05) and Mexican patients (aOR: 1.84 95%CI: 1.27-2.66). Mediator analyses further revealed that disparities persisted even after adjusting for socioeconomic status in Mexican patients (healthcare unaffordability - aOR: 1.65 95%CI: 1.14-2.40) and patients of Central/South American heritage (healthcare unaffordability – aOR: 1.99 95%CI: 1.23-3.21; general financial stress – aOR: 2.97 95%CI: 1.71 – 5.17). Conclusions: Our study highlights significant disparities in the financial impact of cancer treatments on Hispanic patients. Disaggregation by Hispanic country of origin illustrates differences within the Hispanic and Hispanic-American population and reveals specific groups that may be at particular risk of financial harm. Targeted interventions to improve health care access and affordability are needed to increase equity and improve outcomes.
Racial disparities in receipt of guideline-concordant care for early-onset colorectal cancer in the U.S.
Authors: Nogueira Leticia M. , May Folasade , Yabroff K. Robin , Siegel Rebecca
Published: June 2022

6544

Background: Early-onset colorectal cancer patients who are Black are less likely to survive than white patients, even for early-stage disease, possibly due to differences in receipt of guideline-concordant care. This study evaluated racial disparities in receipt of timely and guideline-concordant colon and rectal cancer care in a large nationwide sample. Methods: Non-Hispanic Black and white individuals aged 20-49 years newly diagnosed with colorectal cancer during 2004-2019 were selected from the National Cancer Database. Patients who received all care recommended by the National Comprehensive Cancer Network (staging, surgery, lymph node evaluation, chemotherapy, and radiotherapy) for which they were eligible according to cancer subsite and clinical and pathological TNM stage were considered guideline concordant. Demographic characteristics (age and sex), comorbidities, and health insurance coverage type were added sequentially to a series of multivariable models to estimate contribution to racial disparities in receipt of guideline-concordant care. Racial disparities in time from diagnosis date (among rectal cancer patients eligible for neoadjuvant chemotherapy) and surgery date (among colon cancer patients eligible for adjuvant chemotherapy) to date of chemotherapy initiation was evaluated using restricted mean survival time. Results: Of the 84,728 colon and 62,483 rectal cancer patients, 20.8% and 14.5% were Black, respectively. Black patients were less likely to receive guideline concordant care than white patients diagnosed with colon and rectal cancer, respectively (Table). Demographic characteristics and comorbidities combined explained less than 5% of the disparity, while health insurance coverage type explained 28.6% and 19.4% of the disparity among colon and rectal cancer patients, respectively. Restricted mean time to chemotherapy was statistically significantly longer among Black than white patients for colon (54.0 vs 48.7 days, p <.001) and rectal cancers (49.6 vs 40.9 days, p <.001), respectively. Conclusions: Black patients diagnosed with early-onset colorectal cancer receive worse and less timely care than their white counterparts. Differences in health insurance coverage type, a modifiable factor, were the largest identified contributor to the racial disparities in receipt of guideline-concordant care, suggesting that improved access to care could help mitigate disparities in cancer outcomes. [Table: see text]
Rural-urban disparities in cancer mortality in the United States from 1999 to 2019.
Authors: Hussaini Syed , Blackford Amanda L. , Gupta Arjun
Published: June 2022

6553

Background: U.S. cancer outcomes have improved in recent years, but it is unclear if these gains are realized in all geographic areas. We investigated US rural-urban disparities in age-adjusted cancer mortality rates (AAMRs) over a 20-year period. Methods: We identified cancer deaths from 1999 to 2019 in the CDC WONDER database. We classified populations into large metropolitan (≥1 million), small-or medium-sized metropolitan (50,000-999,999), and rural (<50,000) areas based on the 2013 U.S. Census classification. We calculated annual AAMRs per 100,000 individuals and stratified results by age, sex, and race/ethnicity. We estimated annual percentage changes (APC) in AAMR using robust linear regression models of the log-scale AAMR, including population size as weights, and assessed differential changes over time by geographic area with interaction tests. Results: There were 12,935,840 deaths attributed to cancer (50% large metropolitan, 31.2% medium/small metropolitan, and 18.7% rural). AAMRs were highest in rural areas with least annual improvement. AAMR in large metropolitan areas decreased from 204.5 to 142.6 (APC -1.74 (95% CI [-1.78, -1.7])), and in rural areas it decreased from 209 to 168.3 (APC -1.05 (95% CI [-1.09, -1])) (P <.001 for time trend). The absolute difference in AAMRs between large metropolitan and rural areas increased 5-fold, from 4.5 in 1999, to 25.7 in 2019. This trend was larger in elderly (>65), where rural-urban disparity grew 25-fold (P < 0.001). Non-Hispanic Blacks had higher AAMR than other racial/ethnic groups, and women had lower AAMR than men. Conclusions: In this national analysis of 20 years, rural residents suffered higher cancer mortality than their metropolitan counterparts resulting in widening disparities. Our findings inform program interventions possible through the recent reignition of the Cancer Moonshot in achieving geographic parity, and support ongoing congressional policy deliberations to increase access through re-investment in rural infrastructure.[Table: see text]
Racial/ethnic disparities of cancer treatment disruptions among patients with breast cancer with SARS-CoV-2 infection: An analysis of the ASCO Survey on COVID-19 in Oncology Registry.
Authors: Islam Jessica Yasmine , Hathaway Cassandra , Lee Kimberley T , Hume Emma , Turner Kea , Hallanger-Johnson Julie E. , Tworoger Shelley , Camacho-Rivera Marlene
Published: June 2022

6556

Background: The COVID-19 pandemic has led to disruptions in cancer treatment delivery among breast cancer patients in the U.S. However, it is currently unknown whether racial/ethnic disparities exist in cancer treatment disruptions among patients with breast cancer and SARS-CoV-2 infection. Methods: We obtained data from the ASCO Survey on COVID-19 in Oncology Registry (March 2020-July 2021) describing breast cancer patients diagnosed with SARS-CoV-2 during their care treated at 46 practices across the US. Data included patient demographics, SARS-CoV-2 diagnosis and treatment, breast cancer characteristics, and modifications to cancer treatment plans. Breast cancer treatment delay or discontinuation (TDD) was defined as any treatment postponed more than two weeks from the originally scheduled date. We computed adjusted odds ratios (aOR) using multivariable logistic regression, accounting for non-independence of patients within hospitals to evaluate racial/ethnic disparities of TDD. Multivariable models were adjusted for age, sex, number of comorbidities, cancer extent, ECOG performance score, pandemic period based on case peaks ( < 06/2020, 06-12/2020, 01-07/2021), and COVID-19 severity (death/hospitalization/ICU admission/mechanical ventilation). Results: Breast cancer patients (n = 804) with SARS-CoV-2 were mostly aged 50 years and above (75%) and urban residents (83%). The racial/ethnic makeup of the sample included: 13.3% non-Hispanic Black/African American (NH-Black), 11.7% Hispanic/Latinx, 4.9% American Indian/Alaskan Native (NH-AI/AN), 4.6% NH-Asian, and 65% NH-White. At SARS-CoV-2 diagnosis, 736 patients (91%) were scheduled to receive drug-based therapy (78%), radiation therapy (8%), or surgery (6%), of whom 39% experienced TDD. Across treatment modalities, the most commonly reported TDD reason from the clinic perspective was the patient’s COVID-19 disease (̃90%). Overall, NH-Black (62%), Hispanic/Latinx (44%), and NH-Asian (42%) adults with breast cancer and SARS-CoV-2 were more likely to experience TDD versus NH-White adults (34%) (p < 0.001). In multivariable analyses, NH-Black cancer patients were more likely to experience TDD compared to NH-White patients (aOR: 3.12, 95% CI: 1.96-5.47). The data suggest Hispanic/Latinx (aOR: 1.34, 95% CI: 0.78-2.30) breast cancer patients may also experience TDD, although not statistically significant. No association was observed among NH-Asian (aOR: 1.16, 95% CI: 0.50-2.73) or NH-AI/AN (aOR: 0.64, 95% CI: 0.28-1.52) breast cancer patients with TDD. Conclusions: Black or African American breast cancer patients are more likely to experience cancer care disruptions during the pandemic. Future research should evaluate the long-term impacts of care disruptions on breast cancer outcomes among minoritized US communities.
Readmission risk identification: Implementation of a patient-centered interview.
Authors: Reinbolt Raquel E. , Moline Taylor , Rader Julie , Nilsson Rhonda , Garnett Doris , Liebner Nicole , Graham Lisa
Published: June 2022

6564

Background: Unplanned 30-day readmissions in the cancer population are common. There are few large studies describing cancer patients’ readmission perspective. To better define predisposing factors associated with readmission, our Nurse Case Manager team implemented a patient-focused survey. Methods: Cancer patients readmitted to The James Cancer Hospital from May 2020-December 2021 were included. Readmission events were defined as an inpatient hospital readmission within 30 days of the patient’s prior hospitalization. Team members conducted a 16-question survey immediately following readmission to evaluate the patients’ perspective on factors that may have contributed to their readmission; results were recorded. Results: A total of 3,333 readmissions were unplanned, 109 planned, 22 listed as other; 3,464 patients completed interviews (Table). During their index admission, most patients reported receiving (90%) and understanding (89%) discharge education/instructions. Upon index discharge, most patients (62%) were discharged on a new medication; the majority reported filling their prescription (95%) and taking it as instructed (98%). Nearly all patients had a post-index hospitalization follow up appointment scheduled, but only 58% reported attending. The primary reason reported for not attending was readmission prior to the appointment. Just over 50% of patients received a post-index hospital stay phone call. Some patients (6% yes; 58% unanswered) felt services at discharge would have been helpful. Most patients (51%) contacted their provider regarding worrisome symptoms experienced prior to being readmitted. Pain (18%), fever (11%), and shortness of breath (10%) were the most commonly reported symptoms that prompted returning to the hospital. Conclusions: To our knowledge, this is the largest study to date of cancer patients’ own perspective of their 30-day readmission. More immediate post-hospitalization follow up and increased deployment of tailored discharge services represent areas of opportunity identified to decrease readmission rates. Symptom-specific interventions may also be impactful. Due to the negative downstream effects readmissions have on the healthcare system, it is critical to develop risk mitigation strategies incorporating patient-reported experience. [Table: see text]
When and how to deliver oncology supportive care resources: An adolescent and young adult perspective.
Authors: Roggenkamp Betty , Mittal Nupur , Rynar Lauren , Duvall Adam , Martinez Denisse , McNeer Jennifer Lynn , Rivard Linda , Roberts Gabrielle , Stepenske Julia , Sanford Stacy
Published: June 2022

6569

Background: The Coleman Supportive Oncology Collaborative for Adolescents and Young Adults (CSOC AYA) is a multi-institution Chicago-based quality improvement collaborative consisting of representation from AYA-focused oncology teams at six hospitals and national patient advocacy organizations. Coping with cancer as an AYA is challenging given their complex and unique phases of life and dichotomy between pediatric and adult care. AYAs with cancer are a recognized underserved population within the cancer community and have unique supportive care needs that are often unmet. The CSOC AYA focuses on improving access to resources for supportive care. Methods: We implemented an online survey across six cancer treatment centers (5 academic, 1 community) engaging 50 AYAs. Participants were newly diagnosed (2), currently on treatment (18), or off treatment (30). Participant age range was representative of AYAs ( < 18years: 2%, 18 – 24: 36%, 25 – 34: 55%, and 35-39: 7%). Reported race was 60% Caucasian, 10% Black, 18% Latino, 8% Asian, 2% American Indian, and 2% other. Questions were asked to inform which supportive resources were desired by patients, when the resources would be most useful during the care continuum, and the preferred methods to receive information. Results: Greater than 54% percent of respondents desire social/emotional resources and peer connection at diagnosis. During treatment and after treatment, > 71% and > 56% respectively, desire guidance regarding nutrition/diet and physical activity/exercise, in addition to social/emotional support and peer connection (See table). Preferred methods to receive information were identified: 72% via email or text, 60% in person, and 45% via a patient portal. Conclusions: The CSOC AYA survey identified the type of supportive care resources AYAs need, when they are wanted, and their preferred methods for receiving them. Optimizing accessibility and availability of supportive care resources can enable AYA self-management and has the potential to improve quality of life. These survey results will serve as the basis for a patient-facing online intervention implemented throughout the care continuum with the intent to improve supportive care access for AYAs with cancer. [Table: see text]
Contemporary real-world associations between performance status and clinical outcomes in patients with cancer: A retrospective cohort study.
Authors: Kumar Deepika , Neeman Elad , Zhu Shiyun , Sun Hongxin , Kotak Dinesh , Liu Raymond
Published: June 2022

6578

Background: The ECOG-PS (Eastern Cooperative Oncology Group Performance Status) scale is often used to guide cancer care, but the degree to which it predicts contemporary real-world clinical outcomes, in general and within certain patient groups, is relatively unknown. This retrospective cohort study examined associations between ECOG-PS levels and adverse outcomes in cancer patients with diverse patient characteristics. Methods: Various patient characteristics and nurse-rated ECOG-PS scores (range: 0-4) were recorded for all 21,730 adult patients with cancer receiving intravenous systemic therapy between 01/01/2017 and 12/31/2019 at 18 Kaiser Permanente Northern California cancer centers. Differences in baseline characteristics by ECOG-PS scores were evaluated using chi-square tests for categorical variables and ANOVA for continuous variables. Univariable and multivariable Cox Proportional Hazard models were used to test the ability of ECOG-PS to predict the occurrence of adverse clinical outcomes, including 1-month emergency department (ED) visits and hospitalizations, and 6-month mortality. Results: Overall, 42.5% of patients had ECOG-PS = 0, 42.5% had ECOG-PS = 1, 10.5% had ECOG-PS = 2, 4% had ECOG-PS = 3 and 0.4% had ECOG-PS = 4. Most patients were women (58%), non-Hispanic White (61%), English speakers (93%) and married/domestic partners (63%). African Americans, men, older patients, and those with higher Charlson comorbidity index or Stage IV cancer were found to have higher ECOG-PS levels (all p < 0.001). In multivariable analysis, ECOG-PS of 3-4 were associated with higher ED visits (HR 3.85, 95% CI [3.47-4.26]), hospitalizations (HR 4.7, [4.12-5.36]) and mortality (HR 7.34, [6.64-8.11]), compared with ECOG-PS = 0. Upper gastrointestinal (GI) and Stage IV cancers were associated with a higher risk of ED (upper GI: HR 2.39, [2.12-2.68], (stage IV: HR 1.31, [1.21-1.42]), hospitalization (HR 2.67, [2.27-3.13], (HR 1.51, [1.35-1.68]), and mortality rates (HR 3.37, [2.97-3.81], (HR 1.82, [1.68-1.98]), compared to Breast and Stage I cancers; however, advanced age was not associated with these outcomes. Interactions between ECOG-PS and cancer type as well as ECOG-PS and age group were statistically significant (p < 0.001), such that ECOG-PS was more predictive of adverse outcomes in younger patients and those with breast cancer. Conclusions: In this contemporary real-world cohort, multivariable analysis showed that ECOG-PS, cancer type and stage were strong predictors of ED visits, hospitalizations and mortality; however, advanced age was not. These results also show that ECOG-PS is more predictive of clinical outcomes in certain patient groups. Our findings may have implications on the use of ECOG-PS for clinical decision making.
Oncologist consideration of patient health insurance coverage and out-of-pocket costs for genomic testing in treatment decision.
Authors: Shi Kewei , Yabroff K. Robin , Zhao Jingxuan , De Moor Janet , Freedman Andrew , Zheng Zhiyuan , Nogueira Leticia M. , Han Xuesong , Klabunde Carrie N.
Published: June 2022

6600

Background: Use of genomic testing, especially multi-marker tumor panels, is increasing in the United States. Not all tests and related treatments are covered by health insurance, which can result in substantial patient out-of-pocket (OOP) costs. Although most patients are concerned about OOP costs, little is known about oncologists’ treatment decisions with respect to patient health insurance coverage and OOP costs for genomic testing. Methods: We identified 1,049 oncologists who reported using multi-marker tumor panels from the 2017 National Survey of Precision Medicine in Cancer Treatment. Separate multivariable ordinal logistic regression analyses were used to assess the associations of oncologist, practice, and patient characteristics and the oncologist ratings of the importance of health insurance coverage and OOP cost for genomic testing as part of treatment decisions. Results: Among oncologists, 47.3%, 32.7% and 20.0% reported that patient insurance coverage for genomic testing was very important, somewhat important, and a little/not important, respectively, in treatment decisions. 56.9%, 28.0%, and 15.2% reported patient OOP costs for genomic testing were very, somewhat, or a little/not important in treatment decisions, respectively. In adjusted ordinal logistic regression analyses, oncologists who used next-generation gene sequencing tests were more likely to report patient health insurance and OOP costs for testing as important (odds ratio (OR) = 2.0; 95% confidence interval (CI): 1.2, 3.5) and (OR = 2.1; 95%CI: 1.2, 3.7), respectively) in treatment decisions. Oncologists with more years of experience, who treated solid tumors (rather than only hematological cancers), worked in practices without molecular tumor boards for genomic tests, and with higher percentages of patients insured by Medicaid or self-paid/uninsured also reported insurance coverage or OOP costs for testing were important in treatment decisions (all p < 0.05). Conclusions: Physician, practice, and patient characteristics were associated with oncologists’ ratings of the importance of patient health insurance and OOP costs in treatment decisions. Identifying factors that influence physicians’ priorities in treatment decisions may inform the development and targeting of interventions to support patient and physician discussions about oncology care.
Efficacy and safety results from ASCEMBL, a phase 3 study of asciminib versus bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIs): Week 96 update.
Authors: Rea Delphine , Mauro Michael J. , Hochhaus Andreas , Boquimpani Carla , Lomaia Elza , Voloshin Sergey , Turkina Anna G. , Kim Dong-Wook , Apperley Jane , Cortes Jorge E. , Sasaki Koji , Kapoor Shruti , Allepuz Alex , Quenet Sara , Bédoucha Véronique , Minami Yosuke
Published: June 2022

7004

Background: Asciminib is the first BCR::ABL1 inhibitor to specifically target the ABL Myristoyl Pocket (STAMP). In the ASCEMBL primary analysis, asciminib had superior efficacy and better safety/tolerability than BOS in pts with CML-CP after ≥2 prior TKIs. After a median follow-up of 2.3 years (16.5 months’ additional follow-up since primary analysis), we report efficacy and safety results (cutoff: October 6, 2021). Methods: Eligible pts were adults with CML-CP after ≥2 prior TKIs, with intolerance or lack of efficacy per 2013 European LeukemiaNet. Pts were randomized 2:1 to asciminib 40 mg twice daily or BOS 500 mg once daily, stratified by major cytogenetic response (MCyR) status (Ph+ metaphases ≤35%) at baseline. The key secondary endpoint was major molecular response (MMR) rate at wk 96. Results: 233 pts were randomized to asciminib (n=157) or BOS (n=76). At cutoff, treatment was ongoing in 84 (53.5%) and 15 (19.7%) pts, respectively; the most common reason for discontinuation was lack of efficacy in 38 (24.2%) and 27 (35.5%) pts, respectively. MMR rate at wk 96 (per ITT) was higher on asciminib (37.6%) than BOS (15.8%). The difference, adjusting for baseline MCyR, was 21.7% (95% CI, 10.5%-33.0%; 2-sided P=.001). More pts on asciminib than BOS, respectively, had BCR::ABL1IS ≤1% (45.1% vs 19.4%) at wk 96. The probability of maintaining MMR and BCR::ABL1IS ≤1% for ≥72 wk was 96.7% (95% CI, 87.4%-99.2%) and 94.6% (95% CI, 86.2%-97.9%), respectively, on asciminib and 92.9% (95% CI, 59.1%-99.0%) and 95.0% (95% CI, 69.5%-99.3%), respectively, on BOS. Median duration of exposure was 103.1 (range, 0.1-201.1) wk on asciminib and 30.5 (range, 1.0-188.3) wk on BOS. Despite the longer duration of asciminib exposure, safety/tolerability of asciminib continued to be better than that of BOS (Table). No new on-treatment deaths were reported since the primary analysis. Most frequent (>10%) grade ≥3 adverse events (AEs) on asciminib vs BOS were thrombocytopenia (22.4%, 9.2%), neutropenia (18.6%, 14.5%), diarrhea (0%, 10.5%), and increased alanine aminotransferase (0.6%, 14.5%). Conclusions: After >2 years of follow-up, asciminib continued to show superior efficacy and better safety/tolerability vs BOS. Responses were durable, with more pts on asciminib in MMR. Additionally, more pts on asciminib had BCR::ABL1IS ≤1%, a milestone response in later lines associated with improved survival. These results continue to support the use of asciminib as a new CML therapy, with the potential to transform standard of care. Clinical trial information: NCT03106779. [Table: see text]
Enrichment of high-risk innate immune cells in Hispanic and Black children with B-acute lymphoblastic leukemia.
Authors: Gilbert Julie R. , Sabnis Himalee S. , Radzievski Roman , Doxie Deon , DeRyckere Deborah , Castellino Sharon M. , Dhodapkar Kavita M.
Published: June 2022

7021

Background: Black and Hispanic children with B-acute lymphoblastic leukemia (B-ALL) experience worse outcomes compared to their non-Hispanic white (NHW) counterparts. Immune-based therapies have improved the outcomes of children with B-ALL, however, impact of racial/ethnic background on immune microenvironment is less studied. Methods: BM from 61 children with newly diagnosed B-ALL(Hispanic = 21, Black = 17, NHW = 23) was obtained via the Aflac Biorepository. High-dimensional analysis was performed utilizing single cell mass cytometry with 61 markers to characterize T, NK and myeloid cells. Data was analyzed using Cytobank and high-dimensional visualization platforms such as ViSNE. Clinical data including self-reported race/ethnicity and NCI-risk classification were obtained for all samples. Results: Multi-dimensional analysis was carried out for each cell population to dissect race/ethnicity-associated differences. ViSNE clustering of NK cells identified 3 different NK populations, including a distinct population of mature CD57+ NK cells with Tbethi, HLADRhi, granzymeBhi, CD27- phenotype. The distribution of NK subsets was highly impacted by race/ethnicity. Hispanic (H) patients had higher proportions of CD57+ mature NK cells when compared with other groups, (40 ± 4% vs 33 ± 2%; p = 0.03) with pronounced differences apparent within standard risk (SR) patients. H-SR had higher proportion of CD57+ NK cells compared to other SR patients (mean H-SR 43.4 ± 5.87% vs 26.3 ± 2.87% p = 0.0049). ViSNE clustering of myeloid cells identified 5 clusters based on patterns of cell surface markers, including a distinct CD11c+CD16+DRhi inflammatory/non-classical myeloid population. Further analysis showed that NHW-SR patients have significantly lower proportions of CD16+DR+ myeloid cells compared to Hispanic, Black and NHW-HR patients (mean NHW-SR 3.67 ± 2.56% vs Others 10.8 ± 7.87% p = 0.0394). Notably, a phenotypically similar population has recently been implicated in leukemic progression in preclinical models (Witkowski et al, Cancer Cell 2020). In contrast to innate cells, T cell clusters were broadly comparable between different racial/ethnic groups. Conclusions: These studies provide detailed single-cell proteomic analysis and highlight the impact of racial/ethnic background on immune microenvironment in pediatric B-ALL. Our data identify differences in innate immunity with enrichment of high-risk immune-populations in Hispanic and Black children and depletion of inflammatory myeloid populations in NHW-SR children with B-ALL. These variations may contribute to the observed differences in outcomes and may impact application of immune therapies in racial/ethnic groups.
A phase II study of hyper-CVAD with sequential blinatumomab (Blina), with or without inotuzumab ozogamicin (INO), in adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL).
Authors: Short Nicholas James , Kantarjian Hagop M. , Ravandi Farhad , Yilmaz Musa , Kadia Tapan M. , Thompson Philip A. , Konopleva Marina , Ferrajoli Alessandra , Jain Nitin , Sasaki Koji , Alvarado Valero Yesid , Borthakur Gautam , Dinardo Courtney Denton , Ohanian Maro , Macaron Walid , Garris Rebecca , Zhao Min , Kwari Monica , Loiselle Christopher , Jabbour Elias
Published: June 2022

7034

Background: Blina and INO are highly effective in relapsed/refractory B-cell ALL and are associated with high rates of measurable residual disease (MRD) clearance. Use of these agents in the frontline setting may improve outcomes. Methods: Patients (pts) 14-59 years of age with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL, including pts who had received no more than 1 prior cycle of chemotherapy, were eligible. Pts received hyper-CVAD alternating with high-dose MTX/Ara-C for up to 4 cycles, followed by 4 cycles of Blina. Pts with CD20+ disease received 8 doses of an anti-CD20 antibody. Eight doses of IT chemotherapy were given. Maintenance was with alternating blocks of POMP (maintenance cycles 1-3, 5-7, 9-11, and 13-15) and Blina (maintenance cycles 4, 8, and 12). Beginning with pt #39, INO at a dose of 0.3 mg/m2 on day 1 and 8 was added to the 2 cycles of MTX/Ara-C and to 2 cycles of Blina (4 total cycles with INO). Results: Characteristics of the 58 treated pts (38 without INO and 20 with INO) are summarized in Table. Among 45 pts with active disease at study entry, 100% achieved CR. Overall, 76% achieved MRD negativity by flow cytometry after induction and 95% at any time over the course of therapy. The median follow-up of the entire cohort is 26 months (range, 3-61+ months). Overall, 5 pts (9%) relapsed, 18 (31%) underwent transplant in first remission (including an additional 2 pts who relapsed post-transplant), 2 (3%) died in CR, and 33 (57%) remain in continuous remission without transplant. All relapses occurred in pts with established poor-risk features and no relapses have occurred beyond 2 years. For the entire cohort, the estimated 3-year OS is 85% and the 3-year continuous remission duration is 84%. No relapses or deaths have occurred in the INO group, and the estimated 1-year OS is 100%. Treatment was overall well-tolerated. One patient discontinued Blina due to recurrent grade 2 neurotoxicity. No pts have discontinued INO due to toxicity and no cases of veno-occlusive disease have been observed. Conclusions: Hyper-CVAD with sequential Blina is highly effective as frontline treatment of Ph-negative B-cell ALL. The addition of INO to this regimen was safe and early results are encouraging, with no relapses observed to date. Clinical trial information: NCT01371630. [Table: see text]
Impact of prior solid tumor on outcomes of allogeneic hematopoietic stem cell transplantation for AML or MDS.
Authors: Albittar Aya , Portuguese Andrew Jay , Gooley Ted , Deeg H Joachim
Published: June 2022

7048

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers a definitive treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Prior solid tumor (PST) is felt to portend a worse post-transplant prognosis. The aim of this study was to evaluate the impact of PST history on allo-HSCT outcome. Methods: We retrospectively identified patients with AML or MDS who underwent first allo-HSCT at the Fred Hutchinson Cancer Research Center between 2010 and 2018. Cox regression analysis was used to identify factors associated with mortality among patients with PST, and to compare outcomes of patients with and without PST. Multivariable models were fit, adjusting for cytogenetic risk level, time from PST diagnosis to transplant, receipt of reduced-intensity conditioning (RIC), and age at transplant. Survival estimates were obtained using the Kaplan-Meier method. Results: 1198 patients were included for analysis, of which 101 had a history of PST. After a median follow up of 1301 days among survivors, there was a total of 558 deaths and 322 relapses among all patients. Patients with history of PST were older (62.5 vs 54.9 yrs) and a higher proportion received RIC (52.5% vs 27.3%). The most common PSTs included breast (38/101, 38%), prostate (13/101, 13%), colon (9/101, 9%), thyroid (8/101, 8%), and uterine (7/101, 7%). Among those with known staging (n = 66), stage 1 (28/66, 42%) was the most common, followed by stage 2 (17/66, 26%) then stage 3 (15/66, 23%). The most common therapies provided were surgery (95/101, 95%), cytotoxic chemotherapy (41/101, 41%), radiation (45/101, 45%), and endocrine therapy (25/101, 25%). The unadjusted hazard ratio (HR) of mortality in the PST group relative to the non-PST group was 1.10 (95% confidence interval [CI] 0.83-1.47, p = 0.52). After adjustment for patient age, disease, patient/donor CMV status, KPS, cytogenetic risk, source of stem cells, and donor type, the adjusted HR was 0.91 (95% CI 0.68-1.22, p = 0.59). The unadjusted HR for relapse was 1.15 (95% CI 0.79-1.67, p = 0.48), and adjusted HR was 1.11 (0.76-1.11, p = 0.61). Among patients with PSTs, high-risk cytogenetics were associated with increased mortality (adjusted HR = 2.21; 95% CI 1.16-4.2, p = 0.016) and relapse (adjusted HR = 1.91; 95% CI 1.01-3.60, p = 0.047). Longer time from PST diagnosis to transplant led to a numerically increased mortality in the unadjusted (HR = 1.05; 95% CI 1.00-1.11, p = 0.057) and adjusted (HR = 1.05; 95% CI 1.00-1.11, p = 0.69) models treating time as a continuous linear variable. Conclusions: In our study, a history of PST did not impact overall survival or relapse rate among patients who underwent first allo-HSCT for AML or MDS. As in the overall population, post-transplant outcomes were primarily driven by cytogenetic risk level. However, it is likely that selection of patients with PST for transplantation was biased based on overall risk assessment.
Thrombocytopenic myelofibrosis (MF) patients previously treated with a JAK inhibitor in a phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) [MOMENTUM].
Authors: Gerds Aaron Thomas , Verstovsek Srdan , Vannucchi Alessandro , Al-Ali Haifa Kathrin , Lavie David , Kuykendall Andrew T. , Grosicki Sebastian , Iurlo Alessandra , Goh Yeow Tee , Lazaroiu Mihaela Cornelia , Egyed Miklos , Fox Maria Laura , McLornan Donal P. , Perkins Andrew , Yoon Sung-Soo , Gupta Vikas , Kiladjian Jean-Jacques , Donahue Rafe , Kawashima Jun , Mesa Ruben A.
Published: June 2022

7061

Background: MMB, an oral JAK1/2 and ACVR1/ALK2 inhibitor, showed clinical activity on MF symptoms, RBC transfusion requirements (anemia), and spleen volume in the SIMPLIFY trials, including in MF patients (pts) with thrombocytopenia. MOMENTUM is a pivotal phase 3 study of symptomatic and anemic MF pts previously treated with a JAK inhibitor (JAKi) testing MMB vs DAN. This analysis evaluated MOMENTUM pts with baseline (BL) platelet counts (PLT) ≤150 x 109/L. Methods: Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; MF Symptom Assessment Form Total Symptom Score (MFSAF TSS) ≥10; Hgb <10 g/dL; prior JAKi for ≥90 days, or ≥28 days if RBC transfusions ≥4 units in 8 weeks (wks) or Gr 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen ≥5 cm; PLT ≥25 x 109/L. JAKi taper and washout was ≥21 days. Randomization: 2:1 to MMB 200 mg QD plus DAN placebo or DAN 600 mg QD plus MMB placebo for 24 wks. Primary endpoint: TSS response (≥50% reduction from BL) rate at wk 24. Key secondary endpoints, assessed sequentially at wk 24: RBC transfusion independence (TI) rate, splenic response rate (SRR; ≥25% reduction in volume from BL), change from BL in TSS, SRR (≥35% reduction from BL) and rate of zero transfusions since BL. Results: 60 (74%) of 81 MMB pts and 25 (58%) of 43 DAN pts with BL PLT ≤150 x 109/L completed the 24-week randomized treatment (RT) phase. Median BL TSS were 29 (MMB) and 24 (DAN), Hgb were 7.9 (MMB) and 8.0 (DAN) g/dL, and PLT were 67 x 109/L (MMB) and 64 x 109/L (DAN). Prior JAKi was ruxolitinib in 124 pts (100%) and fedratinib in 6 pts (5%). Efficacy results are in Table. These results are consistent with the overall ITT analysis set (N=195). Most common Gr ≥3 TEAEs in the RT phase were thrombocytopenia (MMB, 31%; DAN, 16%) and anemia (MMB, 7%; DAN, 14%); Gr ≥3 bleeding events occurred in 9% of MMB and 5% of DAN pts. TEAEs led to study drug discontinuation in 15% of MMB and 19% of DAN pts in RT phase. A trend toward improved OS up to wk 24 was seen with MMB vs DAN [HR (95% CI)=0.490 (0.195, 1.235)]. Additional analyses of pts with BL PLT <100 x 109/L (N=100) and BL PLT <50 x 109/L (N=31) show similar treatment effects of MMB vs DAN. Conclusions: In thrombocytopenic MF pts who were symptomatic and anemic, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses and showed comparable safety and favorable survival. MMB may address a critical unmet need in thrombocytopenic MF pts. Clinical trial information: NCT04173494. [Table: see text]
Racial disparities affecting Black patients with diffuse large B-cell lymphoma.
Authors: Ermann Daniel Arthur , Vardell Victoria , Fitzgerald Lindsey , Shah Harsh , Stephens Deborah Marie , Hu Boyu
Published: June 2022

7507

Background: Diffuse Large B-cell Lymphoma (DLBCL) is the most common subtype of Non-Hodgkin Lymphoma, with the majority of patients (pts) achieving long-term survival due to the curative nature of frontline therapy. However, limited data exists regarding presentation and clinical outcomes for underrepresented minorities. In this study, we aimed to evaluate the influence of racial identity on overall survival (OS) outcomes for DLBCL pts. Methods: The National Cancer Database was used to identify DLBCL pts diagnosed from 2004-2018. Demographic and treatment characteristics were compared between racial groups. Kaplan-Meier and Cox regression analyses were used to compare OS between Black and white populations. Multivariate analysis and propensity score matching was performed with adjustment for age, stage, co-morbidity score, median income, and insurance status. Results: Of 223,709 DLBCL pts, 87% were white, 8% Black, and 5% other. As compared to white pts at diagnosis, Black pts were younger (mean 56 years [SD ± 16] vs. 66 years [SD ± 15]), more likely to have ≥1 co-morbidity (33% vs. 27%), be HIV-positive (26% vs. 5%), and have both B-symptoms (40% vs. 30%) and stage IV disease (42% vs. 37%) (All p<0.001). In terms of socioeconomic demographics, Black pts were more likely to be uninsured (8% vs. 3%) and be in the lowest median income quartile (43% vs. 15%), but were more likely to receive treatment at academic centers (50% vs. 36%) (all p<0.001). Both Black and white pts had similar IPI scores at diagnosis and were equally likely to receive multi-agent chemotherapy (77% vs. 77%, p<0.001). With a median follow up of 44.9 months, median OS for all treated HIV-negative DLBCL pts was 109 months (range 21-197). Compared to age-matched white pts, Black pts age ≤ 60 had worse median OS (46 vs. 76 months) along with 5- (73% vs. 75%) and 10-year OS (65% vs. 69%) (all p <0.001). Similar results were seen for Black and white pts between the ages of 61-79, but these differences were not demonstrated for pts ≥80 years old (Table). On multivariate analysis, Black race was independently associated with worse OS (HR 1.06, CI 1.01-1.10, p=0.02). Interestingly, the propensity matched analysis demonstrated no significant OS difference between Black and white pts (median 127 vs. 117 months; HR 1.0, CI 0.94-1.06; p=0.90). Conclusions: We present the largest study to date examining racial disparities in DLBCL. This data demonstrates that Black patients have significantly shorter OS compared to white patients, which persists on multivariate analysis. However, this disparity in survival became nonsignificant when patients are equally matched on surrogate markers of healthcare access such as insurance status and median income. Further studies into examining these racial differences are warranted to optimize care for all DLBCL patients. [Table: see text]
Influence of racial and ethnic identity on overall survival in patients with chronic lymphocytic lymphoma.
Authors: Vardell Victoria , Ermann Daniel Arthur , Shah Harsh , Fitzgerald Lindsey , Hu Boyu , Stephens Deborah Marie
Published: June 2022

7508

Background: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and results in highly variable clinical outcomes. Epidemiologically, CLL occurs in White ethnicity more frequently and thus, CLL outcomes among underrepresented minorities are not well studied. We sought to examine differences in treatment patterns and survival outcomes based on racial identity of CLL patients and how these have changed over time. Methods: The National Cancer Database was used to identify CLL patients diagnosed from 2004-2018. Demographic and treatment characteristics were compared between White, Black, Asian, Hispanic and other minority groups. Kaplan Meier and adjusted Cox regression survival analysis were used to compare overall survival (OS) between races. Survival analysis was repeated by year of diagnosis in Black and White populations. Results: Of 97,804 CLL pts identified, 90.7% of patients were White, 7.6% Black (N = 7,391), 2.6% Hispanic (N = 2,487), 0.6% Asian (N = 613), and 1.1% were other. Compared to White pts, Black pts were younger at diagnosis (median age 66 years [interquartile range 61-79] vs. 70 years [range 58-75], more likely to have ≥1 comorbidity (27.9% vs. 21.3%), and be uninsured (6.6% vs. 2.1%) (all p < 0.001). Black pts were more likely than White pts to have CLL directed treatment immediately after diagnosis (35.9% vs 23.6%; p < 0.001). With a median follow-up of 4.3 years, median OS for all CLL patients was 9.0 years (CI 8.9-9.1 years). Black pts had a shorter median OS of 7.0 years (CI 6.7-7.3 years) compared to White pts (9.14 years [CI 9.0-9.3]), p < 0.001), as well as inferior OS at 5-years (61% vs. 69%) and 10-years (36% vs. 46%), p < 0.001. On multivariate analysis adjusted for age and Charlson-Deyo score, Black race was independently associated with shorter OS (HR 1.51 [CI 1.46-1.57], p < 0.001). While OS lengthened with successive year of diagnosis for all races, the relative survival of Black compared to White pts did not improve over the observed time period. Referenced to the White population, Black pts diagnosed between 2004-2006 had a HR of 1.64 (CI 1.52-1.76) for mortality, and those diagnosed between 2016-2018 had a HR of 1.64 (CI 1.44-1.85). Conclusions: We present the largest study to date describing racial disparities in CLL. Black pts have significantly shorter OS compared to White pts, which is sustained when adjusted for the higher prevalence of comorbidities in the Black CLL population. Unfortunately, the survival gap between White and Black patients has not improved since 2004, highlighting the need for targeted research directed at improving survival in Black pts with CLL. [Table: see text]
Four-year follow-up from a phase 2 study of obinutuzumab, ibrutinib, and venetoclax in CLL.
Authors: Rogers Kerry Anne , Huang Ying , Abruzzo Lynne , Bhat Seema Ali , Doong Tzyy-Jye , Kittai Adam , Lozanski Arletta , Lozanski Gerard , Lucas Margaret , Maddocks Kami J. , Mao Charelen , Nussbaum Megan , Sass Ellen J , Suresh Swetha , Byrd John C. , Woyach Jennifer Ann
Published: June 2022

7540

Background: Targeted agent combinations for chronic lymphocytic leukemia (CLL) have resulted in safe regimens with improved progression-free survival (PFS) compared to chemoimmunotherapy. The optimal regimen and long-term outcomes remain unknown. We conducted a phase 2 study of obinutuzumab (OBIN), ibrutinib (IBR), and venetoclax (VEN) in relapsed/refractory (RR) and treatment-naïve (TN) CLL patients (pts) and report extended follow up on two previously reported cohorts (RR, TN 1) and a new cohort of identically treated TN pts (TN 2). Methods: Pts with TN or RR (≥1 prior treatment) CLL requiring treatment were eligible. Treatment was given for 14 28-day cycles (C). OBIN was started C1, IBR C2, and VEN C3 with standard dose escalation. Response was assessed 2 months (mos) after C14 (EOT) by iwCLL 2008 criteria. Minimal residual disease (MRD) was measured by 10-color flow cytometry with a cutoff of < 1x10-4. The primary endpoint was complete remission (CR) with undetectable MRD (uMRD) in blood and bone marrow at EOT. A sample size of 25 pts per cohort achieves 90% power to test the null hypothesis of 10% against 30% with 1-sided α of 10%. The Kaplan-Meier method was used to estimate PFS and overall survival (OS). Results: 75 pts were treated in 3 cohorts (Table). Data are as of 1/3/2022. In the TN 2 cohort, the overall response rate (ORR) at EOT was 96% (95% CI: 80-100) and CR with uMRD was 20% (95% CI: 7-41). The ORR for TN 1 and TN 2 combined was 90% (95% CI: 78-97) and CR with uMRD was 24% (95% CI: 13-38). Median follow up was 56 (0-65), 57 (7-63), and 30 (24-35) mos, respectively, for RR, TN 1, and TN 2. There were 3 deaths (RR = 1, TN 1 = 1, TN 2 = 1) and 6 disease progressions (RR = 4, TN 1 = 2, TN 2 = 0). Estimated 48-month PFS for TN 1 and RR cohorts were both 96% (95% CI: 72-99) and OS was 85% (95% CI: 60-95) and 100%, respectively. The estimated 24-month PFS and OS for TN 2 were both 96% (95% CI: 75-99). The most frequent adverse events were neutropenia (95%, 73% grade ≥3), leukopenia (95%, 45% grade ≥3), lymphopenia (93%, 40% grade ≥3), and thrombocytopenia (91%, 28% grade ≥3). The only grade ≥3 non-hematologic toxicity occurring at ≥20% was hypertension (85%, 39% grade ≥3). Atrial fibrillation occurred in 11% of pts. Conclusions: At extended follow-up, remissions remain durable after fixed duration OBIN, IBR, and VEN. The efficacy and acceptable safety justify further study and are being compared to IBR and OBIN in 2 phase 3 US cooperative group trials. Clinical trial information: NCT02427451. [Table: see text]