Faculty Bibliography

Transformed follicular lymphoma (tFL) is typically associated with chemotherapy resistance and a poor prognosis. There are limited data regarding outcomes after CD19-directed chimeric antigen receptor T-cell (CAR T) therapy in relapsed/refractory (R/R) tFL. A total of 923 adult patients with R/R tFL who received commercial CD19 CAR T therapy between 2017 and 2023 were identified in the Center for International Blood and Marrow Transplant Research registry. Median age was 64 years (range: 30-86) and median prior lines of therapy was 4 (range: 1-18). Most patients (78%) received axicabtagene ciloleucel, with 67% of patients having resistant disease at the time of CAR T infusion. At a median follow-up of 25 months (range: 1-72) from CAR T infusion, the 2-year overall survival (OS) was 57% (95% CI: 53-60) and progression-free survival (PFS) was 43% (95% CI: 40-47). The 2-year cumulative incidences of relapse or progression (rel/prog) and non-relapse mortality (NRM) were 47% (95% CI: 44-51) and 9% (95% CI: 7-11), respectively. The overall response rate to CAR T was 76%, with a complete response rate of 63%. Grade ≥ 3 cytokine release syndrome (CRS) was observed in 7.1% and grade ≥ 3 immune effector cell-associated neurologic syndrome (ICANS) in 21.6% of patients. Multivariable analysis suggested that resistant disease status at the time of CAR T, use of bridging therapy, and high comorbidity index ≥ 3 were associated with inferior PFS and OS. Older age ≥ 60 significantly increased the risk of NRM. Our study suggests that CD19 CAR T is effective and safe for tFL.

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.

Primary effusion lymphoma (PEL) is a rare kind of extranodal non-Hodgkin large B-cell lymphoma that develops in the liquid phase in serous membrane-lined body cavities (perineum, pericardium, and pleura) without tumor masses. Kaposi sarcoma-associated human herpesvirus 8 (HHV8) is essential in establishing a diagnosis of PEL. An 84-year-old male with a past medical history of testicular cancer in his 40s presented with a chief complaint of shortness of breath which was attributed to a left pleural effusion. The flow cytometry indicated 32% small T lymphocytes (cluster of differentiation [CD]4: CD8 = 4.0:1), 9.0% small B lymphocytes without surface light chain expression, and 16% unknown phenotypic large cells. The cell block demonstrated large atypical lymphocytes with irregular nuclear membranes and coarse chromatin. The cells exhibited prominent nucleoli and relatively basophilic, abundant amphophilic cytoplasm. Multinucleated and Reed-Sternberg-like cells were also seen. We performed a panel of immunomarkers including HHV8 and ALK1. The tumor cells were positive for CD45, CD20, and HHV8 and negative for all other markers. Based on morphologic and immunophenotypical features, a diagnosis of PEL is rendered. Positron emission tomography/computed tomography showed an absence of fluorodeoxyglucose uptake in the lymph nodes and the spleen. Given his age, the patient started on treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone at reduced doses (R-miniCHOP) and had a complete response. To our knowledge, there are no other reported cases of complete remission following an attenuated R-miniCHOP protocol in this clinical scenario.

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.