bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual and institutional predictors of sexual orientation and gender identity data collection in oncology practice: An ASCO survey.
Authors: Kamen Charles Stewart , Quinn Gwendolyn P. , Garrett-Mayer Liz , Kaltenbaugh Melinda , Maingi Shail , Meersman Steve C. , Merrill Janette K. , Pratt-Chapman Mandi L. , Schabath Matthew B. , Schenkel Caroline , Chang Shine
Published: June 2021

6520

Background: Most oncology practices do not collect patients’ sexual orientation (SO) or gender identity (GI) (SOGI), prohibiting assessment of sexual and gender minority (SGM) patients’ cancer disparities and identification of such patients in cancer care or research. Studies report that 90% of SGM patients would disclose their SOGI, while 78% of clinicians believe that patients would not. Preliminary evidence indicates that SOGI disclosure improves health outcomes. Organizations, including ASCO and NIH, have called for routine SOGI data collection, but institutional barriers, e.g. lack of SOGI fields in EMRs, hinder progress. This study aimed to delineate institutional and individual-level factors related to SOGI data collection in oncology. Methods: From Oct to Nov 2020, an anonymous 54 item online survey was distributed to ASCO members via direct outreach, listservs and social media. The survey assessed whether respondents’ institutions collect SOGI data, factors related to SOGI data collection, respondents’ attitudes about SOGI data and SGM patients, and demographics. Simple and multiple logistic regression modeling determined factors associated with respondents’ reports of SOGI data collection at their institutions. Results: Nearly half of 257 respondents reported their institutions collect SO and GI data (42%, 48%, respectively); over a third reported their institutions did not collect SO or GI data (36%, 34%, respectively); and a fifth were unsure (22%, 18%, respectively). Collection of both SO and GI was associated in unadjusted models with leadership support and having resources for SOGI data collection. SO collection was also associated with type of institution, having an SGM family member, and belief that knowing SO is important for providing quality care. GI collection was associated with the respondent’s role, SO, political leaning, past SGM training, and belief that knowing GI is important for providing care. Odds ratios (OR) from adjusted models with 95% confidence intervals (CI) comparing respondents who reported SO or GI collection as “Yes” vs. “No” are reported (comparisons to “Unsure” not presented). Most respondents (79%) felt it was important to know both SO and GI to provide quality care, while 14% felt neither was important. Conclusions: Whether or not institutions collect SOGI data is related to many factors. Despite limited statistical power, the same three factors emerged as drivers of data collection: leadership support, resources and individuals’ attitudes. These are critical and possibly self-reinforcing elements for collecting SOGI data.[Table: see text]
Socioeconomic status variables contribute to the disparities in female triple negative breast cancer outcome in the United States, 2011-2015: A population study based on NCI Surveillance, Epidemiology and End Results (SEER) database.
Authors: Wang Zikun , Dong Yi , Lu Zheyu , Chen Zhongxue
Published: June 2021

6521

Background: Cancer disparities pertinent to socioeconomic status (SES) still exist in the American healthcare system. How SES variables impact the outcome of triple negative breast cancer (TNBC) needs identification. Methods: We enrolled 22,434 women diagnosed with invasive TNBC in 2011 – 2015 from the SEER 18 program. The primary outcome was to identify SES risk factors for TNBC cause specific survival (TNBCCSS)and overall survival (OS) via the Cox Proportional Hazard Regression Model. SES information was collected: race, insurance status, marital status, and percentage of families with incomes below the poverty level and adults with less than high school graduate (<HSG) in a county of the patient’s residency; all analyses were also adjusted for clinicopathological characteristics. We categorized rates of poverty and <HSG as quartiles. Results: 18,578 (82.8%) women were insured or insured/ no specifics (NS), and 3,360 (15.0%) received Medicaid upon TNBC diagnosis; only 496 (2.2%) patients were uninsured. The TNBCCSS rates of insured, insured/ NS, Medicaid, and uninsured cohorts were 86.6%, 83.6%, 77.4% and 73.2%, respectively. In multivariable adjusted analyses, the TNBC cause specific mortality risk of patients who were uninsured or receiving Medicaid was significantly higher than that of women who were insured (Hazard ratio [HR] = 1.60, 95% confidence interval [CI]: 1.34-1.92 and HR = 1.29, 95% CI: 1.18-1.41, respectively). Women residing in a county with a high poverty rate (the 3rd quartile [rate of 11.1 – <14.3%]) had significantly worse TNBC cause specific mortality risk as compared to women with residency of the lowest poverty rate (HR = 1.25, 95% CI: 1.10-1.41). Single and widowed cohorts had better HR of TNBCCSS compared with the married population (HR = 0.86, 95% CI: 0.79-0.95 and HR = 0.82, 95% CI: 0.73-0.93, respectively). Notably, we observed a synergistic effect among race, insurance status and TNBC OS: black women receiving Medicaid had significantly lower HR compared with their non-Hispanic white counterparts (HR = 0.86, 95% CI: 0.74-0.98). Rate of <HSG was marginally correlated with the TNBCCSS. Conclusions: SES variables contribute to the disparities in TNBC survival. TNBC cause specific mortality risk of patients without insurance or with Medicaid at the time of TNBC diagnosis is 60% and 29% higher compared with insured women (Table). Race and insurance status act synergistically upon TNBC OS.[Table: see text]
Association of electronic-health record (EHR)-derived race with BRCA testing in patients (pts) with breast cancer (BC) with similar genetic ancestry (GA) in a clinicogenomic database (CGDB).
Authors: Jin Yanling , Fruchtenicht Charlotta , Hu Sylvia , Allen Janis , Meyer Anne-Marie , Ewing Altovise , Huntley Melanie
Published: June 2021

6524

Background: Disparities in health outcomes can be affected by biological factors associated with GA and social determinants of health. These factors can be teased apart using GA data from comprehensive genomic profiling (CGP) in pts with cancer. CGDBs that link EHR data with CGP enable the selection of pts with similar GA. Holding GA constant provides an opportunity to directly study the effects of reported race in health disparities. This study evaluated a published racial disparity (BRCA testing rates in African American [AA] vs White pts with BC) in a population with fixed, similar GA. Methods: The nationwide (US-based) deidentified Flatiron Health and Foundation Medicine (FMI) BC CGDB (Q3 2020) was used. For each pt, GA fractions from 5 geographic ancestry groups (African [AFR]; Admixed American; East Asian; European [EUR]; South Asian) were derived by FMI using an admixture analysis workflow using genes captured in the CGP assay. To focus on BRCA testing in AA vs White pts and find a sufficient population with similar GA but AA or White race, pts with admixture of both EUR and AFR ancestry were selected. The chosen fractions were: Cohort 1=35%-65% AFR and EUR each; Cohort 2=25%-60% AFR and EUR each; Cohort 3=30%-60% AFR. Cohorts overlap but were chosen to increase sample size. In each cohort, documented BRCA testing prevalence, time from diagnosis to BRCA test date, age at BRCA test and overall survival (OS) were compared between races. Other race (OR) and missing race (MR) were also reported. Results: Most pts (4130/6903) in the BC CGDB had ≥75% EUR ancestry; 129 pts had AFR ancestry fractions ≥25% with EUR ancestry >0%. AA pts had the lowest BRCA testing rates (39%, 43%, 44% for Cohorts 1-3, respectively), which were 18%, 10% and 17% lower compared with White pts, respectively (Table). In Cohorts 1-3, AA pts experienced a longer median time between diagnosis and testing (399, 668, 900 days) compared with White pts (93, 667, 106 days). The median age at BRCA test was 16, 9 and 8 years younger in AA pts (49, 47 and 50 years) compared with White pts. Although pts with MR data had the lowest OS compared with the other races within each cohort, the sample size of each arm for all cohorts was too small to make conclusions. Conclusions: This study demonstrated that when holding GA constant, racial disparities persist in BRCA testing patterns and outcome in pts with BC from a CGDB. With increasing availability of linked clinical and genomic data, further exploration of disparities in genetically similar cohorts can provide deeper insight for cancer outcomes and health disparities research.[Table: see text]
Disparity in telehealth and emergency department use among Medicaid and commercially insured patients receiving systemic therapy for cancer in Washington State following the COVID-19 Pandemic.
Authors: Ramsey Scott David , Panattoni Laura Elizabeth , Li Li , Sun Qin , Fedorenko Catherine R. , Sanchez Hayley , Kreizenbeck Karma L. , Shankaran Veena
Published: June 2021

6546

Background: Washington was the first US state to experience the COVID-19 pandemic. Transmission risks and patient fears of visiting oncology practices during its onset resulted in rapid adoption of telehealth services. We hypothesized that the pandemic would widen disparities in oncology practice visits between Medicaid and commercially insured patients, resulting higher rates of emergency department (ED) visits during initial treatment. Methods: Linking Washington State SEER records with Medicaid and commercial insurance enrollment and claims records, we compared adults age <65 with new solid tumor malignancies who received systemic treatment at academic and community oncology practices. Persons starting therapy March – June 2020 (COVID) were compared with those starting therapy March-June 2017-2019 (Pre-COVID). Poisson regressions were used to evaluate differences in oncology practice office visits and telehealth visits. Logistic regressions were used to evaluate the likelihood of at least one ED admission among patients starting systemic therapy pre- and post-COVID. Results: Among patients who met inclusion criteria (652 Commercial, 349 Medicaid), Medicaid enrollees had more advanced disease and more comorbidity versus commercial enrollees. In unadjusted analysis of E&M and telehealth service visit codes, office-based visits fell for both insurance groups (Table) while telehealth service visits (negligible pre-COVID) were higher for commercial versus Medicaid enrollees post-COVID. The proportion of persons with ≥ 1 ED visit during therapy fell for both insurance groups. In Poisson models, Medicaid enrollees had significantly fewer total visits (P=0.001) and fewer telehealth visits (p<0.001) compared commercial enrollees during the COVID period. In the logit models, ED visits trended lower for both groups after COVID (OR 0.53 95% CI 0.279 to 1.008). Among Medicaid enrollees, persons ages 40-49 and breast cancer patients were more likely to visit the ED. Among the commercially insured, persons with 2 or more comorbidities were more likely to visit the ED. The pre-post COVID change in likelihood of an ED visit was not significantly different between insurance groups (p=0.355). Conclusions: In Washington State, the COVID-19 pandemic created a substantial disparity in access to office-based and telehealth care for low-income patients receiving systemic therapy for new cancers. Reduced oncology practice visits among Medicaid patients did not widen existing disparities in utilization of emergency care.[Table: see text]
Disruptions to U.S. medical oncology care during the COVID-19 Pandemic: CancerLinQ Discovery (CLQD) analysis.
Authors: Jazieh Abdul-Rahman , Riffon Mark , King Jennifer C. , Rocque Gabrielle Betty , Paskett Electra D. , Potter Danielle M.
Published: June 2021

6547

Background: The COVID-19 pandemic disrupted all facets of healthcare delivery including cancer care. This study evaluates the disruptions to US medical oncology practice during the pandemic in terms of number and type of patients (pts) encounters to determine the impact on continuity of patient care. Methods: We conducted a retrospective cohort analysis using the CLQD electronic health record database, containing data from 2+ million pts from all 50 states. We assessed changes in the monthly proportions of visit encounter types (in-person outpatient [IPOP] and telehealth [TE]) for new and established patients (NP and EP) with an invasive malignancy, benign or in situ neoplasm, or benign hematology diagnosis having an encounter between 1/1/2018 and 9/30/2020. Results: 781,945 pts were studied. Median age on 1/1/2018 was 64 years (IQR: 53-73), 38% were female, and 58% had an invasive malignancy. From 12/2019 to 9/2020, total monthly encounters dropped from 157,964 to 90,662. Monthly IPOP visits for NP dropped from 11.2% to 7.9%, an absolute drop of 3.3% and a relative drop of 30%; TE for NP increased by 1.1% (Table). Monthly IPOP visits for EP, as a percentage of all visits, dropped from 94.4% to 86.6% from 12/2019 to 6/2020 but rebounded to 90.4% by 9/2020. Fraction of TE increased substantially during the pandemic period reaching a peak in 6/2020 (13.8% for EP and 1.6% for NP) and decreased in 9/2020 to 9.6% and 1.1% for EP and NP, respectively. Compared to non-Hispanic patients, Hispanic patients had a larger reduction in IPOP and more TE during the study period. Percentage of monthly encounters, by type, from baseline*. Conclusions: We observed a reduction in the absolute number and monthly percentage of IPOP encounters during the COVID-19 pandemic. For EP, increases in TE does not fully compensate for reductions in IPOP. The reduction in IPOP NP encounters is particularly concerning since it was not accompanied by a compensatory increase in TE. The reduction in NP is consistent with reported pandemic-associated reductions in cancer screening and suggest a notable delay in cancer diagnoses during the pandemic. Reduction in Hispanic IPOP encounters warrants further evaluation.[Table: see text]
Effect of income on patient decision-making in localized prostate cancer.
Authors: Shen Xinglei , Cao Ying , Katz Aaron J. , Usinger Deborah , Walden Sarah , Chen Ronald C.
Published: June 2021

6552

Background: Socioeconomic status affects goals of care and treatment choices. We investigated the impact of low household income on diagnosis, goals of care, and treatment choice in patients with localized prostate cancer. Methods: The North Carolina Prostate Cancer Comparative Effectiveness & Survivorship Study (NC ProCESS) is a population-based cohort of prostate cancer patients identified at the time of diagnosis, enrolled from 2011-2013, and followed prospectively. Sociodemographic information and decision making factors including goals of care were collected by patient report. Patients were asked to rate the importance of quality of life, cure, burden to friends and family, cost, and effect on daily activity as well as which of these goals was the most important in their treatment decision making. Annual household income was stratified in to 3 levels: < 40K (low), 40-90K (middle),>90K (high). Results: Of 1382 patients, 539 (39%), 553 (40%), and 290 (21%) reported low, medium, and high household income. Lower income patients were less college educated, more frequently unemployed, and had higher rates of either no insurance or government sponsored insurances. Low income patients had higher PSA and worse clinical stage at diagnosis. In goals of care, low income patients more frequently rated high importance on burden (78.8% vs 76.0% vs 65.2% p<0.01) and cost of cancer (61.2% vs 38.5% vs 14.5% p<0.01), and factors other than cure as the most important treatment decision factor. While overall treatment rate at 1 year was similar by income group, the type of treatment differed. On multivariate analyses, adjusting for age, race, clinical risk group, employment, insurance, and treatment goal, high income was associated with increased odds of having surgery (OR 1.81, CI 1.16 – 2.81), and reduced odds of having radiation (0.60, CI 0.36-0.99). Conclusions: Poor patients with low household income have worse prostate cancer at diagnosis. These patients have different goals of care which impact their choice of treatment. These findings provide novel insight into disparities in diagnosis and outcome in prostate cancer.[Table: see text]
Long-term trend of quality-adjusted time without symptoms or toxicities (Q-TWiST) of nivolumab+ipilimumab (N+I) versus sunitinib (SUN) for the first-line treatment of advanced renal cell carcinoma (aRCC).
Authors: Motzer Robert J. , Choueiri Toni K. , May Jessica , Kwon Youngmin , Rusibamayila Nifasha , Botteman Marc , Hamilton Melissa , Ejzykowicz Flavia , Cella David
Published: June 2021

6568

Background: After a minimum follow-up of 48 months (mos), the CheckMate 214 trial (phase 3, NCT02231749) continued to demonstrate a significant overall (OS) and progression-free (PFS) survival benefit for N+I vs. SUN in aRCC patients (pts) with intermediate (I) or poor (P) International Metastatic RCC Database Consortium (IMDC) risk factors (median OS: 48.1 vs. 26.6 mos, HR: 0.65, 95% confidence interval [95% CI]: 0.54, 0.78; 48-mos PFS: 32.7% vs. 12.3%, HR: 0.74, 95% CI: 0.62, 0.88) (Albiges et al. ESMO Open 2020). To further understand the clinical benefits and risks of N+I vs. SUN, we evaluated the Q-TWiST over time using up to 57 mos of follow-up in CheckMate 214. Methods: OS was partitioned into 3 states: time with any grade 3 or 4 adverse events (TOX), time without symptoms of disease or toxicity (TWiST), and time after progression (REL). The Q-TWiST is a metric that combines the quantity and quality (i.e., “utility”) of time spent in each of the 3 states TWiST, TOX, and REL. Prior research (Revicki et al, Qual Life Res, 2006) has established that relative gains in Q-TWiST (i.e., Q-TWiST gain divided by OS in SUN) of ≥ 10% and ≥ 15% can be considered as “clinically important” and “clearly clinically important”, respectively. Non-parametric bootstrapping was used to generate 95% CIs. To observe changes in quality-adjusted survival gains over time, absolute and relative Q-TWiST were calculated up to 57 mos at intervals of 12-mos. Results: With 57-mos follow-up, compared to SUN pts, N+I pts (N = 847) had significantly longer time in TWiST state (+7.1 mos [95% CI: 4.2, 10.4]). The between-group differences in TOX state (0.3 mos [95% CI: -0.2, 0.8]) and REL state (-1.2 mos [95% CI: -4.1, 1.5]) were not statistically significant. The Q-TWiST gain in the N+I vs. SUN arms was 6.6 mos (95% CI: 4.1, 9.4), resulting in a 21.2% relative gain. Q-TWiST gains progressively increased over the follow-up period and exceeded the “clinically important” threshold around 27 mos (Table). These gains were driven by steady increases in TWiST gains from 0.4 mos (after 12 mos) to 7.1 mos (after 57 mos). Conclusions: In CheckMate 214, N+I resulted in a statistically significant and “clearly clinically important (≥ 15%)” longer quality-adjusted survival vs. SUN, which increased over the longer follow-up time. Q-TWiST gains were primarily driven by time in “good” health (i.e., TWiST), which largely resulted from the long-term PFS benefits seen for N+I vs. SUN. Clinical trial information: NCT02231749. [Table: see text]
Post-intervention lung cancer screening compliance among internal medicine resident physicians at a primary care clinic in Hartford, Connecticut.
Authors: Lopetegui-Lia Nerea , Condit Daniel , Castor Lima Gian Carlo , Drekolias Dimitrios , Hundal Jasmin , Jafri Syed Imran Mustafa , Vredenburgh James
Published: June 2021

6569

Background: Lung cancer (ca) screening has shown to reduce mortality by up to 20%.Despite this, only 4% of eligible patients in the US undergo screening. Our initial analysis revealed that 18.3% of patients who met screening criteria had an appropriately ordered LDCT scan, with an 8.7% completion rate. The aim of this study was to improve lung ca screening compliance following the USPSTF guidelines among residents from the University of Connecticut Internal Medicine (IM) residency program at a Clinic in Hartford, Connecticut. Methods: Care provided to patients by an IM resident at the Gengras Clinic were included. After initial data was gathered, we implemented an intervention to improve screening compliance between October 2019 and March 2020, when SARS-CoV-2 pandemic occurred and routine services were interrupted. USPSTF screening guidelines were emailed monthly to residents and attendings; they were reminded of the importance of lung ca screening; updating the pack-year smoking history; as well as instructions on correctly ordering LDCT and documenting shared decision making, which is needed for insurance approval. In-person reminders also occurred at the clinic. Results: Post-intervention, 601 charts were reviewed. 168/601 (27%) patients met screening criteria. 433 patients were excluded due to unclear pack-year, did not meet screening criteria, were deceased or last seen at the clinic prior to the intervention. 63/168 (37.5%) met the criteria and had an appropriately ordered LDCT; 51/168 (30.35%) had a completed LDCT in chart. The remaining 12/168 (7.14%) with an appropriately ordered LDCT, had it scheduled at the time of data collection or it had been cancelled for unclear reasons. 20 patients’ LDCT was ordered by their pulmonologist. 94 (62.5%) who met screening criteria did not have a LDCT ordered. 11 patients with a smoking history, who did not meet screening criteria had a LDCT ordered because of clinical suspicion for cancer. Lastly, 4/168 (2.4%) had a diagnosis of personal history of lung ca. Conclusions: After our educational intervention, patients who qualified had an increase of LDCT being ordered (37.5% from 18.3%) and completed (30.3% from 8.7%). This is, to our knowledge, the first study of its kind. We identified areas of improvement that were key to achieving higher screening rates: educating all residents and attendings on lung ca screening guidelines; educating patients on the importance of undergoing screening tests; creating a best practice advisory in the electronic medical record system that reminds provider to input pack-year smoking history and if the criteria for screening is met, a pop-up prompting the provider to order LDCT; obtaining insurance approval; and lastly, stressing the importance on screening and overall outcomes.
A review of evidence supporting NCCN category 2B off-label recommendations for determination of Medicare reimbursement eligibility.
Authors: DiScala Molly Erin , Carson Kenneth Robert , Grad Gary Irving , Mahon Brett
Published: June 2021

6576

Background: Antineoplastic indications supported by a category 1 or 2A NCCN recommendation are reimbursed by insurance and Medicare, as are FDA-approved indications. While initial reimbursement requests for “off-label” NCCN category 2B indications may be denied, Medicare will reimburse off-label antineoplastic use supported by evidence from a peer-reviewed publication from one of 26 designated journals. Here, we evaluated the published clinical evidence supporting NCCN category 2B indications. Methods: Category 2B drug indications for the 10 most common solid tumor types were identified in the NCCN compendium (n=104). The results were then filtered to include drugs with only category 2B indications in a particular tumor type (n=14). Similarly, FDA-approved indications were excluded, resulting in a list of drugs with only a 2B indication that are not FDA approved in the specified cancer type (n=8). Published clinical studies supporting these category 2B indications were assessed for study type and journal name in PubMed, and journal names were cross-referenced with the CMS-supported list. Results: Among the 8 non-FDA-approved drug indications with only category 2B recommendations, 7 (87%) had at least one publication of a clinical trial in one of the 26 designated journals. The only 2B indication without supporting literature was single-agent gemcitabine hydrochloride in bladder cancer. For further details, see Table. Conclusions: These results suggest that clinicians should consider pursuing the appeals process and provide supporting evidence in cases of claim denial. While coverage is not guaranteed, the evidence supporting 2B indications frequently meets the criteria identified in the Medicare statute. Further studies will evaluate if these findings extrapolate to less common tumor types.[Table: see text]
Clinical trial representativeness and treatment intensity in a real-world sample of women with early-stage breast cancer.
Authors: Caston Nicole E. , Williams Courtney , Franks Jeffrey , Aswani Monica S. , Azuero Andres , Gidwani Risha , Rocque Gabrielle Betty
Published: June 2021

6584

Background: Early stage breast cancer (EBC) treatment is used in women of all ages, races, and health states. However, as clinical trials often do not represent real-world populations, the extent to which evidence-based treatments are prescribed to populations not well represented in these trials is not known. This study evaluated treatment intensity for patients traditionally well represented, underrepresented, and unrepresented in clinical trials. Methods: This retrospective cohort study used the nationwide de-identified electronic health record derived Flatiron Health database for patients diagnosed with EBC between 2011-2020. We categorized treatments as either high- (AC-TH [doxorubicin, cyclophosphamide followed by paclitaxel or docetaxel, trastuzumab]; ACT [paclitaxel or docetaxel, doxorubicin, cyclophosphamide]; TCH [paclitaxel or docetaxel, carboplatin, trastuzumab]; TCHP [paclitaxel or docetaxel, carboplatin, trastuzumab, pertuzumab]) or low-intensity (AC [doxorubicin, cyclophosphamide]; TC [paclitaxel or docetaxel, cyclophosphamide]; TH [paclitaxel or docetaxel, trastuzumab]). Unrepresented patients often have one or more comorbidities and/or prior cancer; underrepresented patients are typically Black, Indigenous, people of color, or of age extremes ( < 45, 70+); well represented patients are White and between the ages of 45-69. Odds ratios (OR), predicted proportions, and 95% confidence intervals (CI) from a two-level (patients nested in practice) hierarchical logistic regression model evaluated associations between receipt of high-intensity chemotherapy and patient characteristics of clinical trial representation (age, race/ethnicity, presence of comorbidity). Results: Our study included 970 patients with EBC with 13%, 45%, and 41% characterized as unrepresented, underrepresented, and well represented in clinical trials, respectively. In the adjusted model, those aged ≥ 70 vs 45-69 had lower odds of receiving a high-intensity treatment (OR 0.40, 95% CI 0.26-0.60), while those aged < 45 vs 45-69 had higher odds of receiving high-intensity treatment (OR 1.82, 95% CI 1.10-3.01). The predicted proportion of patients receiving a high-intensity treatment was 87% (95% CI: 80%-92%) for patients aged < 45, 79% (95% CI: 74%-84%) for patients aged 45-69, and 60% (95% CI: 50%-70%) for patients aged ≥ 70. Neither race/ethnicity nor comorbidity status were associated with odds of receiving high-intensity chemotherapy. Conclusions: Over half of the EBC population is not well represented in clinical trials. Age was associated with differential treatment intensity, despite a lack of evidence that these differences are appropriate. Widening clinical trial eligibility criteria is one way to better understand survival outcomes, identify potential toxicities, and ultimately make evidence-based treatment decisions using a more diverse sample.
Efficacy and cost-effectiveness of breast cancer (BC) screening in female survivors of childhood Hodgkin lymphoma (HL).
Authors: Wong Florence Lennie , Lee Janie M. , Leisenring Wendy M. , Neglia Joseph Philip , Howell Rebecca M. , Smith Susan A. , Oeffinger Kevin C. , Moskowitz Chaya S. , Henderson Tara O. , Mertens Ann , Nathan Paul C. , Yasui Yutaka , Landier Wendy , Armstrong Gregory T. , Robison Leslie L. , Bhatia Smita
Published: June 2021

6593

Background: Female childhood HL survivors treated with ≥10 Gy of chest radiation are at high risk of developing BC. The Children’s Oncology Group (COG) guidelines recommend lifetime annual mammography (MAM) and breast Magnetic Resonance Imaging (MRI) starting 8y after chest radiation or age 25, whichever is later, and clinical breast examination (CBE) annually from puberty and semiannually from age 25. Initial model results suggest that CBE adds no survival benefit in this cohort. Digital breast tomosynthesis (DBT) is increasingly replacing digital MAM in clinical practice. Here, we present the efficacy and cost-effectiveness of COG’s imaging-based screening recommendations. Methods: Life-years (LYs), quality-adjusted LYs (QALYs), BC mortality, and costs (2017 U.S.$) were estimated from simulating the lifetimes of 5-million chest-irradiated 25y old HL survivors who underwent BC screening with each of the following strategies: annual digital MAM, MRI, MAM+MRI, annual DBT or DBT+MRI from age 25 onward. Treatment-related BC risk (in-situ and invasive) and non-BC mortality were estimated from female 5y HL survivors in the Childhood Cancer Survivor Study and from U.S. population rates. Test sensitivity was 70-74% for MAM (based on prior HL studies) and 89% for DBT and MRI (based on women at high risk of de novo BC). Costs and quality of life weights were obtained from medical literature. Results: For HL survivors with no screening, lifetime BC risk was 42.7% and BC mortality was 18.1%. BC risk and non-BC mortality were, respectively, 7.4- and 5.2-fold higher at age 50 in HL survivors relative to the general population. Screening at ages 25-74 had similar LY gain and BC mortality reduction compared to lifetime screening; hence, we focused on screening for ages 25-74. For all strategies screening provided LY gain of 0.34-0.47 and reduced BC mortality by 6.7-9.8% compared with no screening; incremental cost-effectiveness ratio (ICER), or cost per QALY gained, for MAM alone was $58,726 and for DBT alone was $62,989. ICER of adding MRI to MAM ($385,285) or to DBT ($513,358) indicated lower cost-effectiveness of supplemental MRI (Table). Conclusions: Annual screening at ages 25-74y in chest-irradiated HL survivors appears beneficial. Using $100K per QALY gained as cost-effectiveness threshold, annual MAM or DBT are more cost-effective, whereas adding MRI to MAM is less cost-effective.[Table: see text]
OPTIC primary analysis: A dose-optimization study of 3 starting doses of ponatinib (PON).
Authors: Cortes Jorge E. , Apperley Jane , Lomaia Elza , Moiraghi Beatriz , Undurraga Sutton Maria , Pavlovsky Carolina , Chuah Charles , Sacha Tomasz , Lipton Jeffrey Howard , Schiffer Charles , McCloskey James K. , Hochhaus Andreas , Rousselot Philippe H. , Rosti Gianantonio , De Lavallade Hugues , Mauro Michael J. , Hall Tracey , Lu Vickie , Srivastava Shouryadeep , Deininger Michael W
Published: June 2021

7000

Background: PON, a third-generation tyrosine kinase inhibitor (TKI), demonstrated deep and long-lasting responses and survival in patients (pts) with chronic-phase chronic myeloid leukemia (CP-CML) resistant/intolerant to second-generation TKI therapy (PACE; NCT01207440); post hoc analysis suggested a relationship between dose and both adverse events and response. Here we present the primary analysis of OPTIC (NCT02467270), an ongoing, randomized, phase 2 trial with a novel response-based dosing regimen of PON in pts with resistant/intolerant CP-CML. Methods: Pts with CP-CML resistant/intolerant to ≥2 TKIs or with the BCR-ABL1 T315I mutation were randomized to PON starting doses of 45 mg (cohort A; 45 mg → 15 mg), 30 mg (B; 30 mg →15 mg), and 15 mg (C) once daily. Doses were reduced to 15 mg with achievement of ≤1% BCR-ABL1IS in cohorts A and B. The primary endpoint is ≤1% BCR-ABL1IS at 12 mo; secondary endpoints include cytogenetic and molecular responses and safety outcomes. AOEs were adjudicated prospectively by an independent review committee. Results: 283 pts were randomized (A/B/C: n=94/95/94) and had the following baseline characteristics: median age 48 y (18‒81 y); 98% received ≥2 (55% ≥3) TKIs; 99% had resistant disease; 40% had ≥1 baseline mutations (23% T315I). At the primary analysis with 32 mo median follow-up, 134 pts (47%; n=50/41/43) remained on treatment and 204 pts (72%) had PON exposure ≥12 mo. At 12 mo, 44% (41/93) in A, 29% (27/93) in B, and 23% (21/91) in C achieved ≤1% BCR-ABL1IS (Table); primary endpoint was met by cohort A. Dose reductions to 15 mg after achieving response (A/B) were 48/29%. Most common grades ≥3 TEAEs were thrombocytopenia, 27%; neutropenia, 17%; and anemia, 7%. AOEs/serious AOEs were reported in cohorts A (10%/4%), B (5%/4%), and C (3%/3%). Dose reductions or discontinuations for TEAEs (A/B/C) were 46/35/32% and 19/16/14%, respectively. Conclusions: The OPTIC primary analysis demonstrates the optimal benefit:risk profile for PON was achieved with a response-based dosing regimen starting with 45 mg/d, followed by dose reduction to 15 mg/d upon achieving ≤ 1% BCR-ABL1IS; 30 mg→15 mg and 15 mg cohorts may provide benefit, especially in pts without T315I mutation (Table). The observed ≤1% BCR-ABL1IS responses are supported by robust survival outcomes in pts with CP-CML resistant to second-generation BCR-ABL1 TKI therapy, both with and without BCR-ABL1 mutations. Clinical trial information: NCT02467270. [Table: see text]
Letermovir prophylaxis and cytomegalovirus reactivation in adult allogeneic hematopoietic cell transplant recipients with graft versus host disease.
Authors: Wolfe Delaney , Zhao Qiuhong , Siegel Emma G , Puto Marcin M , Efebera Yvonne Adeduni , Tossey Justin C
Published: June 2021

7004

Background: Cytomegalovirus (CMV) is the most common clinically significant infection after allogeneic hematopoietic-cell transplantation (allo-HCT) and is associated with increased mortality. The risk for CMV reactivation increases with HLA mismatch, high dose corticosteroids, and graft versus host disease (GVHD). GVHD contributes to significant morbidity and mortality and is treated with immunosuppressive therapies that further increase CMV infection risk. In a phase III trial, letermovir prophylaxis had a lower incidence of CMV infection post-allo-HCT in patients at high risk of CMV reactivation when compared to placebo when given up to day +100. There is a lack of data concerning the effectiveness of letermovir in patients who develop GVHD and may continue letermovir past day +100. Methods: This was a single-center, retrospective study conducted at The Ohio State University. Demographics and transplant details were collected from medical records. The primary outcome was incidence of clinically significant CMV infection (CS-CMVi) within 200 days of allo-HCT. Secondary outcomes included incidence of CMV viremia, duration of letermovir therapy, mortality, and risk factors for CS-CMVi. Early death without CMV was treated as a competing risk for CS-CMVi, while relapse was a competing risk for non-relapse mortality (NRM). Proportional subdistribution or Cox hazards models were used to evaluate the association between use of letermovir and risk of CS-CMVi, NRM, or overall survival (OS) adjusting for potential confounding factors, where use of letermovir and GVHD were treated as time-dependent variables. Results: A total of 262 CMV-seropositive patients who received an allo-HCT between June 1, 2016 and June 30, 2020 were included. Of these, 119 patients received letermovir prophylaxis. A total of 111 patients received treatment for CS-CMVi, which included 82 of 143 (57%) who did not receive letermovir compared to 29 of 119 (24%) who received letermovir. Incidence of CMV viremia was significantly reduced with the use of letermovir in all patients (HR 0.21, 95% CI 0.12–0.34, p < 0.001) and among patients with acute GVHD grade >2 within 200 days post-allo-HCT (HR 0.12, 95% CI 0.05–0.32, p < 0.001), adjusting for age, gender, GVHD prophylaxis and use of ATG or T-cell depleted graft. The median duration of letermovir therapy was 97 days. Nine patients were continued on letermovir indefinitely for recurrent CMV viremia. Patients who received letermovir had decreased NRM (HR 0.41, 95% CI 0.18-0.96, p = 0.04) and improved OS (HR 0.46, 95% CI 0.23-0.95, p = 0.04). Conclusions: Letermovir prophylaxis significantly decreased CS-CMVi and improved NRM and OS in this real-world analysis. In addition, patients with acute GVHD had significantly less CMV viremia, suggesting potential benefit in continuing letermovir prophylaxis in this patient population.
Second-line bosutinib (BOS) for patients (pts) with chronic phase (CP) chronic myeloid leukemia (CML): Final 10-year results of a phase 1/2 study.
Authors: Gambacorti-Passerini Carlo , Brümmendorf Tim H. , Kim Dong-Wook , Goh Yeow Tee , Dyagil Irina S , Pagnano Katia , Batai Arpad , Turkina Anna G. , Leip Eric , Purcell Simon , Leone Jocelyn M , Viqueira Andrea , Cortes Jorge E.
Published: June 2021

7009

Background: BOS is approved for Philadelphia chromosome (Ph)+ CML resistant/intolerant to prior therapy and newly diagnosed Ph+ CP CML. In a phase 1/2 study, second-line BOS showed durable efficacy and manageable toxicity in pts with imatinib-resistant (IM-R) or -intolerant (IM-I) Ph+ CP CML. Methods: This final efficacy and safety analysis of the phase 1/2 study and extension study was based on ≥10 y of follow-up (FU). Ph+ CP CML pts who received BOS starting at 500 mg/d after prior treatment (Tx) with imatinib only were included. Results: 19% of pts were on BOS at y 10, and 13% were still on BOS at study completion after ≥10 y; 19% completed ≥10 y of FU. Median duration of Tx and FU were 26 and 54 mo, respectively. Median (range) dose intensity was 436 (87–599) mg/d. The most common primary reasons for permanent Tx discontinuation were lack of efficacy (unsatisfactory response or disease progression; 27%) and adverse events (AEs; 26%). In pts with a valid baseline assessment, cumulative complete cytogenetic response (CCyR), major molecular response (MMR) and MR4 rates (95% CI), respectively, were 50% (43–56), 42% (35–49) and 37% (30–44) (IM-R: 48% [41–56], 46% [37–55] and 39% [31–48]; IM-I: 53% [41–64], 36% [25–48] and 33% [22–45]). Responses were durable, with estimated probabilities of maintaining CCyR, MMR and MR4 > 50% after ≥10 y (Table). At 10 y, cumulative incidence of on-Tx progression/death was 24% and Kaplan-Meier (K-M) overall survival 72% (Table); 55 deaths (IM-R: n = 41; IM-I: n = 14) occurred on study, none BOS-related. Any grade Tx-emergent AEs (TEAEs) in ≥40% of pts were diarrhea (86%), nausea (46%) and thrombocytopenia (42%). Pleural effusion, cardiac and vascular TEAEs occurred in 13%, 12% and 11% of pts, respectively. 28% of pts had AEs leading to permanent Tx discontinuation; most common (≥2% of pts) were thrombocytopenia (6%), neutropenia (2%) and alanine aminotransferase increased (2%). Conclusions: These 10-y data are consistent with prior results of durable efficacy and manageable toxicity with second-line BOS and support long-term BOS use in CP CML pts after imatinib failure. Clinical trial information: NCT00261846 and NCT01903733. [Table: see text]
A registry-based, observational safety study of inotuzumab ozogamicin (InO) treatment in patients (pts) with B-cell precursor acute lymphoblastic leukemia (ALL) who proceeded to hematopoietic stem cell transplant (HSCT).
Authors: De Lima Marcos J.G. , Kebriaei Partow , Lanza Francesco , Cho Christina , Giralt Sergio , Popradi Gizelle , Hemmer Michael T , Zhang Xin , Shah Richa , Welch Verna L. , Vandendries Erik , Stelljes Matthias , Marks David I. , Saber Wael
Published: June 2021

7017

Background: InO is a CD22-directed antibody-drug conjugate indicated for treatment of relapsed/refractory (R/R) ALL. InO has been associated with hepatotoxicity and hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), particularly post-HSCT. Registry data (Center for International Blood and Marrow Transplant Research [CIBMTR]) was analyzed to assess toxicity in pts with ALL who received InO prior to HSCT. Methods: CIBMTR patient data are being collected for a 5-year period after US approval of InO (Aug 2017 – Aug 2022). Data from US pts age ≥18 y treated with InO who proceeded to allogeneic HSCT were included. Using interim data at 3 y, we evaluated post-HSCT outcomes, including clinical status, overall survival, transplant-related (non-relapse) mortality (NRM), relapse, death after relapse (time from HSCT to death after the first 28 d from any cause with prior relapse/progression post-HSCT), and investigator-defined adverse events, including hepatic VOD/SOS. All statistical analyses are descriptive. Results: Data accrued from 18 Aug 2017 to 17 Aug 2020 for 131 adult pts (median age 40 y) who proceeded to first allogeneic HSCT: 31% in first complete remission (CR1), 46% in CR2, 13% in ≥CR3, 5% in 1st relapse, 2% in ≥3rd relapse, and 3% in primary induction failure. A majority (70%) had transplants from peripheral blood stem cells, and 47% involved an HLA-identical sibling or other related donor. Nearly half received myeloablative conditioning regimens. Before HSCT, 36% of pts received 1 cycle of InO, 46% had 2 cycles, and 17% had ≥3 cycles. Half (48%) received InO as a single agent. Median time from last dose of InO to HSCT was 2.0 mo (range: 0.4–26.2). At time of data-lock (11 Nov 2020), post-transplant data were available for 131 pts. Outcomes for these pts are shown in the Table. Among a subgroup of adults with active R/R ALL (n = 91) at time of HSCT (median of 4 lines prior therapy), VOD/SOS incidence within 100 d of HSCT was 18%. Conclusions: Incidence of VOD/SOS after first HSCT in InO-treated pts with R/R ALL in this study was similar to the 18–19% reported in pooled analyses of 2 clinical trials among InO-treated pts with R/R ALL (Marks et al, Biol Blood Marrow Transplant 2019) and in the INOVATE study (Kantarjian et al, Lancet Haematol 2017). The NRM at 1 y of 21% (23% R/R ALL) is lower than the NRM at 1 y of 38% reported in the pooled analyses of R/R ALL InO recipients.[Table: see text]
Health-related quality of life (HRQoL) in patients (pts) with myelodysplastic syndromes (MDS) in the Connect Myeloid Disease Registry.
Authors: Revicki Dennis A. , Grinblatt David L. , Komrokji Rami S. , Garcia-Manero Guillermo , Savona Michael R. , Scott Bart L. , Sekeres Mikkael A. , Flick E. Dawn , Makinde Adeola Y. , Kiselev Pavel , Louis Chrystal U. , Nifenecker Melissa , DeGutis Irene S. , Cogle Christopher R.
Published: June 2021

7040

Background: At diagnosis, disease risk and transfusion burden (TB) can impact HRQoL in pts with MDS. The impact of disease status and higher transfusion requirements on HRQoL has not been well studied. We used data from the Connect Myeloid Disease Registry, an ongoing, prospective, observational cohort study that includes adult pts with lower-risk (LR) and higher-risk (HR) MDS, to investigate factors influencing baseline (BL) and subsequent HRQoL. Methods: BL and Month 6 (M6) data from pts enrolled from Dec 12, 2013 to Mar 6, 2020 (data cutoff) were analyzed. Pts were stratified by International Prognostic Scoring System (IPSS) risk (LR, HR), treatment (Tx) within 45 days post-enrollment (no Tx, best supportive care [BSC], active Tx), and TB 16 weeks post-BL (non-transfusion dependent [NTD], low TB [LTB]; 1−3 transfusions, high TB [HTB]: ≥4 transfusions). Pts completed EQ-5D, FACT-An trial outcome index (TOI), and FACT-Fatigue (FACT-F) questionnaires at BL and quarterly thereafter. Clinically meaningful change, based on minimally important differences, was defined as a change of ±0.07 for EQ-5D, ±6 for FACT-An TOI, and ±3 for FACT-F. Results: At data cutoff, 830 (489 LR, 341 HR) pts were enrolled. Median age was 74 years. 278 pts received no initial Tx, 161 BSC, and 378 active Tx. At BL, 470 were NTD, 197 LTB, and 163 HTB. Of 670 pts still on-study at M6, 462 completed the questionnaires at both BL and M6. At BL , clinically meaningful differences were observed in FACT-An TOI and FACT-F scores, but not EQ-5D, between LR- and HR-MDS and the Tx subgroups . From BL to M6, no clinically meaningful changes were observed in mean scores for each questionnaire. For the TB subgroups, meaningful differences were observed at BL in FACT-An TOI and FACT-F scores, but not EQ-5D (Table). From BL to M6, meaningful decreases in scores were reported by 26%, 30%, and 35% of NTD, LTB, and HTB pts in EQ-5D, 41%, 43%, and 48% for FACT-An TOI, and 40%, 42%, and 48% for FACT-F; increases were reported by 19%, 19%, and 20% pts for EQ-5D, 31%, 32%, and 39% for FACT-An TOI, and 30%, 39%, and 40% for FACT-F. Conclusions: This preliminary analysis suggests that pts with HR-MDS, and transfusion-dependent pts, generally had worse HRQoL at BL, providing further support to initiating active Tx in pts with TB. Possible limitations of the analysis are lower completion rates in pts with more severe disease, and EQ-5D may not capture changes in these subgroups at M6. A longer follow-up may help delineate the impact of Tx on HRQoL assessments in pts with MDS. Clinical trial information: NCT01688011. [Table: see text]
First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia.
Authors: Byrd John C. , Hillmen Peter , Ghia Paolo , Kater Arnon P. , Chanan-Khan Asher Alban Akmal , Furman Richard R. , O'Brien Susan M. , Yenerel Mustafa Nuri , Illés Árpád , Kay Neil E. , Garcia Marco Jose Antonio , Mato Anthony R. , Seymour John Francis , Leprêtre Stephane , Stilgenbauer Stephan , Robak Tadeusz , Patel Priti , Higgins Kara , Sohoni Sophia , Jurczak Wojciech
Published: June 2021

7500

Background: Increased selectivity of the Bruton tyrosine kinase inhibitor (BTKi) acalabrutinib (Aca) vs ibrutinib (Ib) may improve tolerability. We conducted an open-label, randomized, noninferiority, phase 3 trial to compare Aca vs Ib in patients (pts) with chronic lymphocytic leukemia (CLL). Methods: Previously treated CLL pts with del(17p) or del(11q) by central lab were randomized to receive oral Aca 100 mg BID or Ib 420 mg QD (stratified by del(17p) status, ECOG PS [2 vs ≤1], and number of prior therapies [1–3 vs ≥4]) until progression or unacceptable toxicity. Primary endpoint was progression-free survival (PFS) as assessed by IRC; secondary endpoints of all grade atrial fibrillation (AF), grade ≥3 infection, Richter transformation, and overall survival (OS) were assessed in hierarchical order. Results: 533 pts (Aca, n=268; Ib, n=265) were randomized (median age 66 y; median 2 prior therapies; del(17p) 45.2%; del(11q) 64.2%). At a median follow-up of 40.9 mo (range 0.0–59.1), Aca was noninferior to Ib with a median PFS of 38.4 mo in both arms (HR 1.00; 95% CI 0.79–1.27). Aca was statistically superior to Ib in all-grade AF incidence (9.4% vs 16.0%; P=0.023). Among the other secondary endpoints, incidences of grade ≥3 infection (Aca: 30.8%, Ib: 30.0%) and Richter transformation (Aca: 3.8%, Ib: 4.9%) were comparable between arms. Median OS was not reached in either arm (HR 0.82 [95% CI 0.59–1.15]), with 63 (23.5%) deaths in the Aca arm and 73 (27.5%) in the Ib arm. Among any-grade AEs in ≥20% of pts in either arm, Aca was associated with a lower incidence of hypertension (9.4%, 23.2%), arthralgia (15.8%, 22.8%), and diarrhea (34.6%, 46.0%) but a higher incidence of headache (34.6%, 20.2%) and cough (28.9%, 21.3%). AEs led to treatment discontinuation in 14.7% of Aca- vs 21.3% of Ib-treated pts. Among any-grade events of clinical interest, cardiac, hypertension, and bleeding events were less frequent with Aca (Table). Conclusions: In this first head-to-head trial of BTKis in CLL, Aca demonstrated non-inferior PFS with less cardiotoxicity and fewer discontinuations due to AEs vs Ib. Clinical trial information: NCT02477696. [Table: see text]