Faculty Bibliography

CONTEXT:Existing research on psychological distress and mental health service utilization has focused on common types of solid tumor cancers, leaving significant gaps in our understanding of patients experiencing rare forms of hematologic cancers. OBJECTIVE:To examine distress, quality of life, and mental health service utilization among patients with aggressive, refractory B-cell lymphomas. METHOD:= 26) with B-cell lymphomas that relapsed after first- or second-line treatment completed self-report measures of distress (Hospital Anxiety and Depression Scale) and quality of life (Short-Form Health Survey, SF-12). Patients also reported whether they had utilized mental health treatment since their cancer diagnosis. RESULTS:= 0.001]. SIGNIFICANCE OF THE RESULTS:A significant proportion of patients with advanced, progressive, B-cell lymphomas may experience elevated levels of distress. Yet, few of these distressed patients receive mental health treatment. Findings highlight the need to better identify and address barriers to mental health service utilization among patients with B-cell lymphoma, including among distressed patients who decline treatment.

PURPOSE:Black and Hispanic individuals with diabetes receive less recommended diabetes care after cancer diagnosis than non-Hispanic Whites (NHW). We sought to determine whether racial/ethnic minorities with diabetes and cancer were at increased risk of diabetes-related emergency department (ED) visits and hospitalizations compared with NHW. METHODS:Using SEER cancer registry data linked to Medicare claims from 2006 to 2014, we included Medicare beneficiaries age 66+ years diagnosed with incident nonmetastatic breast, prostate, or colorectal cancer between 2007 and 2012 who had diabetes. Our primary outcome was any diabetes-related ED visit or hospitalization 366-731 days after cancer diagnosis. Using Fine-Gray subdistribution hazard models, we examined whether risk of ED visits or hospitalizations was higher for racial/ethnic minorities compared with NHW. RESULTS:< .0001). Adjusting for potential confounders, Black (adjusted hazard ratio, 1.22; 95% CI, 1.12 to 1.35) individuals had a higher risk of any ED visit or hospitalization compared with NHW. CONCLUSION:Black individuals with diabetes and cancer were at increased risk for diabetes-related ED visits and hospitalizations in the second year after cancer diagnosis compared with NHW even after accounting for confounders.

Recent first-line randomized controlled trials (RCTs) for patients with diffuse large B-cell lymphoma (DLBCL) have shown negative results, which may be due in part to onerous eligibility criteria limiting enrollment of poor-risk patients who require immediate treatment. We conducted a Delphi-method survey with lymphoma experts in the United States to define recommendations for essential and potentially unnecessary enrollment criteria for modern first-line DLBCL RCTs aimed at increasing clinical diversity of ensuing study groups. We first tabulated enrollment criteria from 19 DLBCL RCTs spanning the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) era to identify common eligibility criteria from prior DLBCL RCTs for inclusion in the Delphi-method survey. We tabulated 451 total eligibility criteria comprising 51 criterion categories across 19 first-line DLBCL RCTs in the R-CHOP era. We then surveyed lymphoma clinical trial experts representing 8 academic medical centers in the United States regarding essential and unnecessary eligibility criteria for modern DLBCL RCTs. Seventeen of 29 invited clinical investigators completed the round-1 questionnaire (response rate, of 58.6%), 15 of 17 round-1 participants (88.2%) completed the round-2 survey, and all round-1 participants reviewed finalized recommendations for eligibility criteria for modern first-line DLBCL RCTs. We defined consensus recommendations for 31 modernized eligibility criteria including threshold values for 10 quantitative eligibility criteria aimed at facilitating enrollment of a clinically diverse study population in first-line DLBCL RCTs designed to improve standard-of-care therapy.

OBJECTIVE:Obtaining electronic patient data, especially from electronic health record (EHR) systems, for clinical and translational research is difficult. Multiple research informatics systems exist but navigating the numerous applications can be challenging for scientists. This article describes Architecture for Research Computing in Health (ARCH), our institution's approach for matching investigators with tools and services for obtaining electronic patient data. MATERIALS AND METHODS/METHODS:Supporting the spectrum of studies from populations to individuals, ARCH delivers a breadth of scientific functions-including but not limited to cohort discovery, electronic data capture, and multi-institutional data sharing-that manifest in specific systems-such as i2b2, REDCap, and PCORnet. Through a consultative process, ARCH staff align investigators with tools with respect to study design, data sources, and cost. Although most ARCH services are available free of charge, advanced engagements require fee for service. RESULTS:Since 2016 at Weill Cornell Medicine, ARCH has supported over 1200 unique investigators through more than 4177 consultations. Notably, ARCH infrastructure enabled critical coronavirus disease 2019 response activities for research and patient care. DISCUSSION/CONCLUSIONS:ARCH has provided a technical, regulatory, financial, and educational framework to support the biomedical research enterprise with electronic patient data. Collaboration among informaticians, biostatisticians, and clinicians has been critical to rapid generation and analysis of EHR data. CONCLUSION/CONCLUSIONS:A suite of tools and services, ARCH helps match investigators with informatics systems to reduce time to science. ARCH has facilitated research at Weill Cornell Medicine and may provide a model for informatics and research leaders to support scientists elsewhere.

Resistance to standard immunochemotherapy remains an unmet challenge in diffuse large B-cell lymphoma (DLBCL), and aberrant DNA methylation may contribute to chemoresistance. Promising early-phase results were reported with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus subcutaneous azacitidine, a hypomethylating agent. In this phase 1 study, we evaluated CC-486 (oral azacitidine) plus 6 cycles of R-CHOP in patients with previously untreated intermediate- to high-risk DLBCL or grade 3B/transformed follicular lymphoma. CC-486 doses of 100, 150, 200, or 300 mg given 7 days before cycle 1 and on days 8-21 of cycles 1-5 were evaluated; additional patients were enrolled in the expansion phase to examine preliminary efficacy. The primary objectives were to determine the safety and the maximum tolerated dose (MTD) of CC-486 in combination with R-CHOP. The most common grade 3/4 toxicities were hematologic, including neutropenia (62.7%) and febrile neutropenia (25.4%); grade 3/4 nonhematologic toxicities were uncommon (<7%). The MTD was not established; 2 patients had dose-limiting toxicities (1 with grade 4 febrile neutropenia; 1 with grade 4 prolonged neutropenia). The recommended phase 2 dose was established as 300 mg. The overall response rate was 94.9%, with 52 patients (88.1%) achieving complete responses. With a median follow-up of 28.9 months, estimated 1- and 2-year progression-free survival rates were 84.1% and 78.6%, respectively. Overall, epigenetic priming with CC-486 before R-CHOP can be delivered with acceptable safety to patients with previously untreated intermediate- to high-risk DLBCL or grade 3B/transformed follicular lymphoma. ClinicalTrials.gov: NCT02343536.

INTRODUCTION:Newly diagnosed indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) patients are often monitored for disease progression to delay the impact of cancer-directed therapy on patients' quality of life. However, research on quality of life in patients under active surveillance versus in cancer-directed treatment has yielded mixed results. This study examined distress and quality of life in indolent NHL/CLL patients in active surveillance or cancer-directed treatment over the first-year post-diagnosis. PATIENTS AND METHODS:Adult patients (≥21 years) with newly diagnosed indolent NHL/CLL completed electronic self-report measure of distress and quality of life every 4 months over the course of a year for a total of 4 surveys. Fisher's exact test and t-tests were used to examine demographic and disease differences between patients receiving different treatments. Mixed-effect models were also used to compare overall differences between treatment status over time, accounting for missing values. RESULTS:The sample consisted of 64 patients with known baseline treatment status who did not change treatments over the course of the study. Total quality of life and physical, social and functional quality of life improved over time in patients receiving cancer-directed treatment and decreased over time in patients under active surveillance. Relative to patients in active treatment, overall, social, and functional quality of life in patients under surveillance changed more slowly over time. DISCUSSION:Active surveillance may have negative implications for patient quality of life, despite that a common goal of active surveillance is to delay the impact of treatment (e.g., appointments, toxicities) on quality of life.

BACKGROUND:Many cancer survivors with co-morbid diabetes receive less diabetes management than their non-cancer counterparts. We sought to determine if racial/ethnic disparities exist in recommended diabetes care within 12 months of an incident breast, prostate, or colorectal cancer diagnosis. Because co-morbid diabetes decreases long-term survival, identifying predictors of guideline-concordant diabetes care is important. METHODS:Using the Surveillance, Epidemiology, and End Results cancer registry linked to Medicare claims, we included beneficiaries aged 67+ years with diabetes and incident, non-metastatic breast, prostate, or colorectal cancer between 2008 and 2013. Primary outcomes were diabetes care services 12 months after diagnosis: (1) HbA1c test, (2) eye exam, and (3) low-density lipoprotein (LDL) test. Using modified Poisson models with robust standard errors, we examined each outcome separately. RESULTS:We included 34,643 Medicare beneficiaries with both diabetes and cancer. Mean age at diagnosis was 76.1 (SD 6.2), 47.2% were women; 35% had breast, 24% colorectal, and 41% prostate cancer. In the 12 months after incident cancer diagnosis, 82.4% received an HbA1c test, 55.3% received an eye exam, 77.8% had an LDL test, and 42.0% received all three tests. Compared to non-Hispanic Whites, Blacks were 3% (95% CI 0.95-0.98) less likely to receive a HbA1c test, 10% (95% CI 0.89-0.92) less likely to receive a LDL test, and 8% (95% 0.89-0.95) less likely to receive an exam eye. Blacks and Hispanics were 16% (95% CI 0.81-0.88) and 7% (0.88-0.98) less likely to receive all three tests, after accounting for confounders. Racial/ethnic differences persisted across cancer types. CONCLUSION:Blacks and Hispanics with breast, prostate, and colorectal cancer and diabetes received less diabetes care after cancer diagnosis compared to non-Hispanic Whites. Differences were not explained by socio-economic factors or clinical need. IMPLICATIONS FOR CANCER SURVIVORS:Our findings are concerning given the high prevalence of diabetes and poor cancer outcomes among racial/ethnic minorities. The next step in this line of inquiry is to determine why minorities are less likely to receive comprehensive diabetes care in order to develop targeted strategies to increase receipt of appropriate diabetes management for these vulnerable populations.

BACKGROUND:Doxorubicin carries a risk of congestive heart failure (CHF). Black race has been suggested as a risk factor for doxorubicin-related cardiotoxicity, but data are limited. We assessed whether HF occurs at higher rates in Black patients compared to White patients who receive doxorubicin for DLBCL, and evaluated race as an independent risk factor for the development of HF after adjusting for known risk factors. PATIENTS AND METHODS:We used SEER-Medicare to identify patients 66 years and older with DLBCL. We excluded patients with CHF documented prior to diagnosis with DLBCL. We assessed for hypertension, type 2 diabetes, coronary artery disease, and arrhythmias prior to diagnosis with DLBCL. The primary outcome was documented CHF at any point following DLBCL diagnosis. Secondary outcomes included CHF in the first year following diagnosis and death. We performed analyses additionally stratified by cumulative dose of doxorubicin. RESULTS:Our study population consisted of 8,604 patients (White 96.8%, Black 3.2%). In both Kaplan-Meier and competing risk analyses, we observed no significant difference in the incidence of CHF between Black and White patients, both before and after adjusting for covariates. Finally, we observed no significant differences in the incidence of CHF by race after stratification by cumulative doxorubicin dose. CONCLUSIONS:CHF is common following doxorubicin chemotherapy for DLBCL in older patients. No association was observed between Black race and the onset of heart failure in this setting. Rigorous screening for known clinical risk factors is likely more relevant than race in treatment selection and optimization.

Autologous (auto-) or allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities for mantle cell lymphoma (MCL). Recently, chimeric antigen receptor (CAR) T-cell therapy received approval for MCL; however, its exact place and sequence in relation to HCT is unclear. The ASTCT, CIBMTR, and the EBMT, jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-, allo-HCT, and CAR T-cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated; in the first-line setting auto-HCT consolidation represents standard-of-care in eligible patients, whereas there is no clear role of allo-HCT or CAR T-cell therapy, outside of a clinical trial. In the R/R setting, the preferential option is CAR T-cell therapy especially in MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T-cell therapy has failed or is not feasible. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL.