Faculty Bibliography

While the advent of chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed or refractory DLBCL, it is unclear how survival has changed at the population level following its approval. Herein, we performed a population-based cohort study using the SEER-17 database. The primary exposure was a period of diagnosis (2014-2017 vs. 2018-2021), and these periods were selected based on the first FDA-approval of CAR-T in 2017. Study outcomes were relative survival (RS), overall survival (OS), lymphoma-specific survival (LSS), and the cumulative incidence of death from lymphoma (CIF). A total of 51,584 patients with DLBCL were included in the study with 24,861 patients diagnosed in time period-1 (2014-2017) and 26,723 patients diagnosed in time period-2 (2018-2021). The median age at diagnosis was 68 years (interquartile range, 57-77) and most patients were White (n = 42,190, 82%) with advanced stage at diagnosis (n = 28,203, 55%). In unadjusted analysis, the 5-year RS (95% CI) increased from 64% from 2014 to 2017 to 66% from 2018 to 2021, while 5-year OS increased from 54 to 55%, and 5-year LSS increased from 64 to 66%. On competing risks analysis, the 5-year probability of death from lymphoma decreased from 34 to 31%. The improvements in survival were observed across age, disease stage, and racial groups, and remained significant when adjusting for age, sex, race, stage, B symptoms and documented receipt of chemotherapy in multivariable survival models (adjusted OS HR = 0.97, 95%CI = 0.94-1.00, p = 0.04; adjusted LSS HR = 0.93, 95%CI = 0.90-0.96, p < 0.001). We found improved survival for patients with DLBCL diagnosed between 2018 and 2021 when compared to those diagnosed between 2014 and 2017. These findings will serve as the benchmark for future studies evaluating the impact of CAR-T administered earlier in their disease course.

PURPOSE/OBJECTIVE:Immune checkpoint inhibitors (ICIs) have revolutionized the care of patients with cancer, but use among hospitalized patients is controversial as a result of questionable benefit and high costs. To evaluate the role of ICIs in the inpatient (IP) setting, we conducted the Inpatient Immunotherapy Outcomes Study (IIOS) to describe characteristics and outcomes of patients who received IP ICIs. METHODS:IIOS is a retrospective study of patients treated with ICIs during hospitalization between 2012 and 2021 at five academic institutions. Data collection was performed using each institution's electronic medical record. We estimated overall survival (OS) from the first administration of ICI using the Kaplan-Meier method and used adjusted Cox proportional hazards models to explore associations between clinicodemographic variables and OS. RESULTS:Two hundred fifteen patients received IP ICIs (median age 60 years; 55% White; 14% Black; 13% Hispanic). Thoracic and head and neck (24%), GI (21%), and hematologic (19%) malignancies were most common. Most of the patients were ICI-naïve (75%), had stage IV solid malignancies (75%) at the time of IP ICI initiation, and had no radiographic response to ICI therapy (88%). Median OS from the first IP ICI dose was 1.55 months (95% CI, 1.08 to 1.81) for all patients and 1.28 months (95% CI, 0.95 to 1.80) for patients with advanced solid malignancies. Multivariable Cox proportional hazards model analysis found no clinicodemographic variables associated with improved OS after IP ICI administration. CONCLUSION/CONCLUSIONS:IIOS is the largest multi-institutional effort to describe outcomes after IP ICI administration. Clinical outcomes are poor after IP ICI use and IP ICIs should be used with caution.

Histologic transformation (HT) of indolent non-Hodgkin lymphoma (iNHL) to diffuse large B-cell lymphoma (DLBCL) carries a poor prognosis. Using the Surveillance, Epidemiology, and End Results-17 database, we conducted a population-based study of adult patients with transformed follicular lymphoma (t-FL), marginal zone lymphoma (t-MZL), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (t-LPL/WM), and de novo DLBCL. Primary outcome was relative survival (RS), and secondary outcomes included overall survival (OS) and lymphoma-specific survival (LSS). Outcomes were modeled using flexible parametric survival models, while multivariable modeling was used to compare RS, OS, and LSS. The incidence of HT was highest in splenic MZL (SMZL, 6.78%) and lowest in extranodal MZL (EMZL, 1.62%). Median follow-up times were similar for patients with de novo DLBCL and transformed indolent lymphomas. The 5-year RS and OS were longer in de novo DLBCL compared to all other transformed iNHL subtypes (68 versus 59%, respectively). For t-FL, early transformation (within 2 years of diagnosis, Hazard ratio [HR] = 1.34) and prior treatment (HR = 1.89) were associated with inferior survival. This association was not observed in other transformed lymphoma subtypes. This is the first comparative study to show that the outcomes of t-LPL/WM were inferior compared to de novo DLBCL and highlights the need to incorporate early experimental therapies in patients with t-FL with early transformation and receipt of prior chemotherapy.

There are limited data assessing the risk scores for primary treatment failure (PTF) in patients with classical Hodgkin lymphoma (cHL; PTF-cHL) undergoing autologous hematopoietic cell transplantation (auto-HCT). ECLIPSE (Evaluation of Classical Hodgkin Lymphoma patients wIth Primary treatment failure and analySis of outcomEs) is a multicenter retrospective cohort of patients with PTF-cHL (aged ≥15 years) diagnosed on or after 1 January 2005, at 15 US medical centers. PTF was defined as 1 of the following patterns of failure: (1) progressive disease by imaging during or within 6 weeks of completion of frontline chemotherapy (primary progression [PP]); (2) partial response (PR) or stable disease (SD) by imaging after completion of frontline treatment (PR/SD); (3) progression of disease by imaging (and confirmed by biopsy) within 12 months of frontline therapy completion after prior documentation of complete response (CR; early relapse [ER]). A total of 478 patients were included in the analysis. Among these, 217 (45%) were PP, 86 (18%) were PR/SD, and 175 (37%) were ER. The 6-month and 1-year cumulative incidence of nonrelapse mortality after auto-HCT were 0.9% and 1.1%, respectively. The median progression-free survival (PFS) and overall survival (OS) after auto-HCT were 4.33 and 10.09 years, respectively. Although those not in CR at the time of auto-HCT were associated with inferior PFS and OS, advanced age and diagnosis before 2011 were associated with inferior OS. This study showcases the safety and long-term efficacy of auto-HCT, even in patients with high-risk disease who are traditionally considered chemotherapy refractory, and will serve as a benchmark for the ongoing transplant vs no transplant trials.

INTRODUCTION/UNASSIGNED:Patients with hematologic malignancies frequently receive elective anticancer therapy as inpatients. The impact of introducing hospitalists on quality outcomes in this subset of patients is unknown. METHODS/UNASSIGNED:Patients with leukemia or lymphoma electively admitted for anticancer therapy to either a hematologist-led service (TS; n=59) or to a hospitalist-led service (HS; n=102) during two parallel 18-month time periods were included. Mixed linear regression models with first-order random effects for intercept (individual) and slope (time) were used to estimate the association between service and the quality outcomes of length of stay (LOS), time from admission to anticancer therapy initiation, and discharge time of day. RESULTS/UNASSIGNED:For patients who received a fixed-duration anticancer therapy regimen, after adjustment for clinical and demographic covariates, mean LOS was reduced by >2 days (TS=5.97 days (95% CI: 5.13, 6.81); HS=3.88 days (95% CI, 3.53, 4.23); p<0.001), mean time from admission to first anticancer therapy administration decreased by 4 hours (TS=8.32 hours (95% CI: 5.72, 10.93); HS= 4.36 hours (95% CI: 3.49, 5.23); p=0.001)), and mean discharge time was similarly decreased by 110 minutes (TS=3:12 PM (95% CI: 2:06 PM, 4:19 PM); HS=1:22 PM (95% CI: 12:48 PM, 1:57 PM); p=0.01)). For regimens that required variable monitoring for post-treatment methotrexate clearance, tumor lysis syndrome, or white blood cell count recovery, no significant difference in outcomes was noted. CONCLUSION/UNASSIGNED:Hospitalist care of patients with hematologic malignancies admitted for elective anticancer therapy may lead to improved quality and efficiency of care.

Population-based data comparing the outcomes of patients with transformed follicular lymphoma (t-FL) and de novo diffuse large B-cell lymphoma (DLBCL) are lacking. The objective of this study was to compare the survival of patients with t-FL and de novo DLBCL diagnosed in the United States between 2010-2018. We hypothesized that patients with t-FL would have an inferior survival compared to patients with de novo DLBCL. The study outcomes were relative survival (RS), overall survival (OS), and lymphoma-specific survival (LSS) compared between t-FL and de novo DLBCL. Flexible parametric survival models were used to estimate the study outcomes. There were 569 cases of t-FL and 44,706 cases of de novo DLBCL. Patients with t-FL had an estimated 5-year RS of 54% [95% confidence interval (CI), 49-59%) compared to 67% (95% CI, 66-67%) for those with de novo DLBCL (adjusted hazard ratio, 1.29; 95% CI, 1.11-1.50; P = 0.001). The corresponding 5-year OS estimates were 49% (95% CI, 44-53%) and 57% (95% CI, 57-58%), respectively (adjusted hazard ratio, 1.23; 95% CI, 1.07-1.42; P = 0.004). The corresponding 5-year LSS estimates were 54% (95% CI, 50-59%) and 66% (95% CI, 65-66%), respectively (adjusted hazard ratio, 1.34; 95% CI, 1.15-1.56; P < 0.001). This population-based registry analysis shows that patients with t-FL continue to have an inferior survival in the modern era and should be prioritized for enrollment in clinical trials.

BACKGROUND:Racial/ethnic disparities in the utilization of hematopoietic cell transplantation (HCT) have been reported for patients with hematologic malignancies, but population-based data are lacking for lymphoma patients. The objective of this study was to determine whether racial and ethnic disparities exist in the utilization of autologous HCT for lymphoma in the United States. METHOD:We used Surveillance, Epidemiology, and End Results data linked to Medicare fee-for-service claims. We included Medicare beneficiaries aged 66+ years with Hodgkin or Non-Hodgkin lymphomas diagnosed between 2008 and 2015. The primary outcome was time-to-autologous HCT. We used Cox proportional hazards models to estimate racial/ethnic differences in utilization. Missing data were handled using multiple imputation with chained equations. RESULTS:We included 40,605 individuals with lymphoma. A total of 452 autologous transplants were performed. In the unadjusted model, Non-Hispanic Black patients were 51% less likely to receive a transplant than Non-Hispanic White patients (95% CI, 0.26-0.96; p = 0.04). After adjusting for age at diagnosis and sex, Non-Hispanic Black patients were 61% less likely to receive a transplant (95% CI, 0.20-0.76; p = 0.01). However, observed differences attenuated and became non-significant after adjustment for socioeconomic factors (adjusted hazard ratio [aHR], 0.62; 95% CI, 0.32-1.21; p = 0.16) and disease-specific factors (aHR, 0.58; 95% CI, 0.30-1.12; p = 0.11), separately. In the fully adjusted model, we also did not observe a statistically significant association between Non-Hispanic Black race/ethnicity and receipt of transplant (aHR, 0.54; 95% CI, 0.28-1.05; p = 0.07). CONCLUSION:In this population-based cohort study of lymphoma patients, Non-Hispanic Black patients were less likely to receive autologous HCT compared to Non-Hispanic White patients, but this difference was partially explained by socioeconomic and disease-specific factors.

There is a paucity of data regarding racial disparities in the survival of patients with indolent non-Hodgkin lymphomas (iNHL) in the contemporary time-period. Hence, we sought to determine whether racial disparities exist in the survival of patients with iNHLs in the US. We included 68 059 adult patients with follicular lymphoma (FL, n = 41 943), marginal zone lymphoma (MZL, n = 22 485), and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM, n = 3631) who were diagnosed in the US between 2000 and 2017. Race was categorized as White, Black, Asian/Pacific Islander, or American Indian/Alaska Native (API/AI). The primary outcome was relative survival (RS), which was estimated using flexible parametric survival models. The RS estimates varied according to race and disease histology but were consistently lower for racial minorities, including those diagnosed during the most recent 5-year time-period of 2012-2017. On multivariable analysis for RS, Black patients with FL had a 32% higher excess mortality rate compared to White patients [adjusted excess hazard ratio (aEHR), 1.32; 95% CI, 1.15-1.51; p < .001], corresponding to a difference of 55 (95% CI, 24-86) excess deaths per 10 000 person-years. For MZL, Black patients had a 40% higher excess mortality rate compared to White patients (aEHR 1.40; 95% CI, 1.18-1.66; p < .001), corresponding to a difference of 62 (95% CI, 26-98) excess deaths per 10 000 person-years. No significant racial differences were detected for patients with WM. The greatest disparity was seen for younger Black patients with FL. Our findings highlight the need for interventions to improve the outcomes of Black patients with iNHLs, particularly younger Black patients with FL.