Impact of Race and Social Determinants of Health on Outcomes in Patients with Aggressive B-cell nHL Treated with CAR-T.

Healthcare disparities driven by multiple social, economic, and/or environmental factors lead to inequalities in health outcomes. CAR-T cell immunotherapy is an effective therapy for relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). However, data are limited on the impact of the convergence of race and social determinants of health on outcomes for patients treated with CAR-T therapy. We examined the impact of interactions between race and insurance type on health care utilization and outcomes in patients treated with CAR-T for aggressive B-NHL. Adult patients with r/r B-NHL treated with CD19 CAR-T were identified between 2015 and 2021 across 13 US academic centers. Insurance type, demographic and clinical data were collected and analyzed via Chi-squared and Kaplan-Meier analysis. Cox multivariable regression (MVA) was used to determine the impact of race/ethnicity and other variables on survival. 466 adult patients were included in our analysis. Median follow-up after CAR-T was 12.7 months. Median progression free survival (mPFS) was longer for Caucasians (11.5 months) than for African Americans (3.5 months, HR 1.56 [1.03-2.4], p=0.04) or Asians (2.7 months, HR 1.7 [1.02-2.67], p=0.04). Differences in median overall survival (mOS) were not significant. For Medicare (n=206) vs Medicaid (n=33) vs private insurance (n=219) vs self-pay (n=7): mPFS was 15.9 vs 4.2 vs 6.0 vs 0.9 months (p<0.001) and mOS was 31.2 vs 12.8 vs 21.5 vs 3.2 months (p<0.001), respectively. Collectively, our multi-center retrospective analysis showed that race and insurance status can impact outcomes for patients treated with CAR-T cell therapy.

Second-Line Chimeric Antigen Receptor T-Cell Therapy in Diffuse Large B-Cell Lymphoma : A Cost-Effectiveness Analysis.

BACKGROUND: First-line treatment of diffuse large B-cell lymphoma (DLBCL) achieves durable remission in approximately 60% of patients. In relapsed or refractory disease, only about 20% achieve durable remission with salvage chemoimmunotherapy and consolidative autologous stem cell transplantation (ASCT). The ZUMA-7 (axicabtagene ciloleucel [axi-cel]) and TRANSFORM (lisocabtagene maraleucel [liso-cel]) trials demonstrated superior event-free survival (and, in ZUMA-7, overall survival) in primary-refractory or early-relapsed (high-risk) DLBCL with chimeric antigen receptor T-cell therapy (CAR-T) compared with salvage chemoimmunotherapy and consolidative ASCT; however, list prices for CAR-T exceed $400 000 per infusion. OBJECTIVE: To determine the cost-effectiveness of second-line CAR-T versus salvage chemoimmunotherapy and consolidative ASCT. DESIGN: State-transition microsimulation model. DATA SOURCES: ZUMA-7, TRANSFORM, other trials, and observational data. TARGET POPULATION: "High-risk" patients with DLBCL. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: Axi-cel or liso-cel versus ASCT. OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (iNMB) in 2022 U.S. dollars per quality-adjusted life-year (QALY) for a willingness-to-pay (WTP) threshold of $200 000 per QALY. RESULTS OF BASE-CASE ANALYSIS: The increase in median overall survival was 4 months for axi-cel and 1 month for liso-cel. For axi-cel, the ICER was $684 225 per QALY and the iNMB was -$107 642. For liso-cel, the ICER was $1 171 909 per QALY and the iNMB was -$102 477. RESULTS OF SENSITIVITY ANALYSIS: To be cost-effective with a WTP of $200 000, the cost of CAR-T would have to be reduced to $321 123 for axi-cel and $313 730 for liso-cel. Implementation in high-risk patients would increase U.S. health care spending by approximately $6.8 billion over a 5-year period. LIMITATION: Differences in preinfusion bridging therapies precluded cross-trial comparisons. CONCLUSION: Neither second-line axi-cel nor liso-cel was cost-effective at a WTP of $200 000 per QALY. Clinical outcomes improved incrementally, but costs of CAR-T must be lowered substantially to enable cost-effectiveness. PRIMARY FUNDING SOURCE: No research-specific funding.

Outcomes of patients with secondary central nervous system lymphoma following CAR T-cell therapy: a multicenter cohort study.

Chimeric antigen receptor T-cell therapy (CAR-T) has been successful in treating relapsed/refractory B-cell lymphomas. However, its role in the treatment of diseases involving the central nervous system (CNS) is not well studied. We performed a multicenter retrospective cohort study to evaluate the outcomes of patients with secondary CNS lymphoma (SCNSL) who received CAR-T. Eligibility required active CNSL at the time of apheresis. The objectives included evaluation of overall survival (OS), progression-free survival (PFS), identification of predictors of complete response (CR) post-CAR-T, and assessment of risk factors for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Sixty-one patients were included in the analysis. The overall response rate was 68% with a CR rate of 57%. In the multivariable analysis, patients who experienced any grade CRS had higher odds of achieving CR (OR = 3.9, 95% CI = 1.01-15.39, p = 0.047). The median PFS was 3.3 months (95% CI = 2.6-6.0 months) with 6- and 12-month PFS rates of 35% and 16%, respectively. The median OS was 7.6 months (95% CI = 5.0-13.5 months) with 6- and 12-month OS rates of 59% and 41%, respectively. Any grade CRS and ICANS were 70% (n = 43) and 57% (n = 34), respectively with grade ≥ 3 CRS and ICANS rates of 16% and 44%. Factors associated with increased risk of CRS and ICANS included receiving axi-cel or having leptomeningeal ± parenchymal + CNS involvement, respectively. Despite achieving high response rates, most patients experience early relapse or death following CAR-T in SCNSL. The current study provides a benchmark for future trials exploring novel therapeutic options in SCNSL.

Association of a Gamified Journal Club on Internal Medicine Residents' Engagement and Critical Appraisal Skills.

Background: Prior literature demonstrates internal medicine residents have suboptimal competence in critical appraisal. Journal clubs are a common intervention to address this skill, but engagement and critical appraisal skill improvement are variable. Objective: We evaluated journal club engagement and critical appraisal skills after implementation of a gamified format. Methods: This was a single-arm study, conducted from July 1, 2020 to June 30, 2021, involving internal medicine residents at 2 US programs. Residents participated in a 12-month gamified journal club that sorted residents into 2 teams. Residents attended an orientation followed by 6 to 10 monthly, hour-long competitions. In each competition, a subset of the resident teams competed to answer a clinical prompt by critically appraising an original article of their choice. A chief medical resident or faculty member moderated each session and chose the winning team, which received a nominal prize of candy. The primary outcome was engagement, measured by a 7-question survey developed de novo by the authors with Likert scale responses at baseline and 12 months. The secondary outcome was critical appraisal skills assessed by the Berlin Questionnaire. Results: Sixty-one of 72 eligible residents (84.7%) completed both engagement surveys. Residents reported statistically significant improvements in most dimensions of engagement, including a higher likelihood of reading articles before sessions (posttest minus pretest score -1.08; 95% CI -1.34 to -0.82; P<.001) and valuing time spent (posttest minus pretest score -0.33; 95% CI -0.55 to -0.11; P=.004). Critical appraisal skills marginally improved at 12 months (posttest minus pretest score -0.84; 95% CI -1.54 to -0.14; P=.02). Conclusions: Our study demonstrates a gamified journal club was associated with improvements in engagement and minimal change in critical appraisal skills.

ASTCT Clinical Practice Recommendations for Transplantation and Cellular Therapies in Diffuse Large B Cell Lymphoma.

Autologous hematopoietic cell transplantation (auto-HCT) has long been the standard approach for patients with relapsed/refractory (R/R) chemosensitive diffuse large B cell lymphoma (DLBCL). However, the advent of chimeric antigen receptor (CAR) T cell therapy has caused a paradigm shift in the management of R/R DLBCL patients, especially with the recent approval of CD19-directed CAR-T therapy in the second-line setting in high-risk groups (primary refractory and early relapse [≤12 months]). Consensus on the contemporary role, optimal timing, and sequencing of HCT and cellular therapies in DLBCL is lacking; therefore, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines undertook this project to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 20 consensus statements with a few key statements as follows: (1) in the first-line setting, there is no role for auto-HCT consolidation for patients achieving complete remission (CR) following R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) or similar therapy in non-double-hit/triple-hit cases (DHL/THL) and in DHL/THL cases receiving intensive induction therapies, but auto-HCT may be considered in eligible patients receiving R-CHOP or similar therapies in DHL/THL cases; (2) auto-HCT consolidation with thiotepa-based conditioning is standard of care for eligible patients with primary central nervous system lymphoma achieving CR with first-line therapy; and (3) in the primary refractory and early relapse setting, the preferred option is CAR-T therapy, whereas in late relapse (>12 months), consolidation with auto-HCT is recommended for patients achieving chemosensitivity to salvage therapy (complete or partial response), and CAR-T therapy is recommended for those not achieving remission. These clinical practice recommendations will serve as a tool to guide clinicians managing patients with newly diagnosed and R/R DLBCL.

Allogeneic transplant following CAR T-cell therapy for large B-cell lymphoma.

Allogeneic hematopoietic cell transplantation (alloHCT) can potentially salvage large B-cell lymphoma (LBCL) patients experiencing treatment failure after chimeric antigen receptor T-cell therapy (CAR T). Nonetheless, data on the efficacy and toxicities of alloHCT after receipt of CAR T are limited. We report a multicenter retrospective study assessing the safety, toxicities, and outcomes of alloHCT in LBCL patients following CAR T failure. Eighty-eight patients with relapsed, refractory LBCL received an alloHCT following anti-CD19 CAR T failure. The median number of lines of therapy between CAR T infusion and alloHCT was one (range, 0-7). Low intensity conditioning was used in 77% (n=68) and peripheral blood was the most common graft source (86%, n=76). The most common donor types were matched unrelated donor (39%), followed by haploidentical (30%) and matched related donor (26%). Median follow-up of survivors was 15 months (range, 1-72). One-year overall survival, progression-free survival, and graft-versus-host disease-free relapse-free survival were 59%, 45%, and 39% respectively. One-year non-relapse mortality and progression/relapse were 22% and 33% respectively. On multivariate analysis, <2 lines of intervening therapy between CAR T and alloHCT and complete response at time of alloHCT were associated with better outcomes. In conclusion, alloHCT after CAR T failure can provide durable remissions in a subset of patients.

Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL.

Most patients receiving chimeric antigen receptor T-cell therapy (CAR-T) for aggressive B-cell non-Hodgkin lymphoma (B-NHL) do not experience a durable remission. Several novel agents are approved to treat relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T. We conducted a multicenter retrospective analysis to describe peri-CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n = 514) from 13 centers treated with CAR-T for B-NHL between 2015-2021 were included in the study. Survival curves were constructed using Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of the variables on survival outcomes. For all patients receiving CAR-T, a greater number of lines of therapy pre-CAR-T apheresis and bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). The median PFS and OS from the time of CAR-T cell infusion were 7.6 and 25.6 months, respectively. From the time of progression post-CAR-T, the median OS was 5.5 months. The median PFS of treatments administered in the first-line post-CAR-T failure was 2.8 months. Patients with refractory disease on day 30 had inferior OS and were less likely to receive subsequent treatment(s) than other patients with CAR-T failure. Allogeneic hematopoietic cell transplantation for selected patients at any time following CAR-T failure led to durable responses in over half of patients at 1 year. These data provide a benchmark for future clinical trials in patients with post-CAR-T cell progression, which remains an unmet clinical need.

Matched Case Control Analysis of Breast Cancer- Specific Factors Affecting Risk of Developing SARS-CoV-2 Infection.

INTRODUCTION: In this retrospective matched case control study, we aim to identify breast cancer-related risk factors associated with developing COVID-19 and describe outcomes of patients with breast cancer diagnosed with COVID-19. METHODS: Women with breast cancer treated at the Medical College of Wisconsin and diagnosed with COVID-19 from March through December 2020 served as cases, and those without COVID-19 within the same timeframe served as controls. Univariate and multivariate comparisons were performed. RESULTS: Twenty-five cases and 77 controls were identified. All cases were fully matched by age, obesity, county, and race. Mean age was 54.6 versus 54.9, body mass index 31.0 versus 31.6, 48% lived in Milwaukee County, and 68% were White. Regarding COVID-19 outcomes, 24.0% (n = 6) of cases were hospitalized, median length of stay was 2 days, 8% (n=2) needed oxygen, 4% (n = 6) were intubated, and 4% (n = 6) died. COVID-19 led to treatment delays in 40% of cases. On univariate analysis, there was no statistically significant difference in hormone receptor status or breast cancer stage. Being on active chemotherapy (OR 5.8, P = 0.043) significantly increased the likelihood of developing COVID-19. CONCLUSIONS: In this matched case control study of patients with breast cancer, active chemotherapy was significantly associated with an increased likelihood of developing COVID-19, with a trend seen for triple negative disease. These findings support continued strict precautions for those on active chemotherapy and warrant further analysis in those with triple negative disease.

Long-term outcomes and predictors of early response, late relapse, and survival for patients treated with bispecific LV20.19 CAR T-cells.

We previously reported results of a first-in-human trial of bispecific LV20.19 chimeric antigen receptor T-cell (CAR-T) therapy, demonstrating high response rates in patients with relapsed, refractory (R/R) B-cell malignancies. We now report two-year survival outcomes and predictors of early response, late relapse, and survival. Patients from the previously reported phase 1 dose escalation and expansion trial of LV20.19 CAR-T therapy (NCT03019055) treated at target dose of 2.5 × 106 cells/kg (n = 16) were included in this updated analysis. Two-year progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. The relationship of in-vivo CAR-T expansion, tumor burden, and effector: target ratio on early response (day 28) and late relapse (>180 days post-CAR-T) were assessed. Exact log-rank testing was performed to evaluate the impacts of clinical variables on survival outcomes. With a median of 31 months (range 27-40) of follow-up, two-year PFS and OS were 44% and 69%. Median PFS and OS were 15.6 months and not reached, respectively. For CAR-naïve large B-cell lymphoma patients (n = 8), two-year PFS and OS were 50% and 75%. No patient with progression experienced dual target antigen (CD19 or CD20) loss on post-relapse biopsy. Lower in vivo expansion was strongly associated with late relapse. Early treatment response was impeded by high metabolic tumor volume and low effector: target ratio. Bridging therapy and higher absolute lymphocyte count on day of CAR-T infusion were associated with inferior survival outcomes. In conclusion, this initial trial of LV20.19 CAR-T demonstrates a signal for favorable long-term outcomes for patients with R/R B-cell malignancies.

Outcomes of Autologous Hematopoietic Cell Transplantation in Older Patients with Diffuse Large B-Cell Lymphoma.

Data for outcomes after autologous hematopoietic cell transplantation (auto-HCT) in diffuse large B-cell lymphoma (DLBCL) patients ≥70 years are limited. Auto-HCT is feasible in older DLBCL patients. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes of auto-HCT in DLBCL patients aged 60 to 69 years (n = 363) versus ≥70 years (n = 103) between 2008 and 2019. Non-relapse mortality (NRM), relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models. All patients received BEAM conditioning (carmustine, etoposide, cytosine arabinoside and melphalan). On univariate analysis, in the 60 to 69 years versus ≥70 years cohorts, 100-day NRM was 3% versus 4%, 5-year REL was 47% versus 45%, 5-year PFS 40% versus 38% and 5-year OS 55% versus 41%, respectively. On multivariate analysis, patients ≥70 had no significant difference in NRM (hazard ratio [HR] 1.43, 95% confidence interval [CI] 0.85-2.39), REL (HR 1.11, 95% CI 0.79-1.56), PFS (HR 1.23, 95% CI 0.92-1.63) compared to patients 60 to 69 years. Patients ≥70 years had a higher mortality (HR 1.39, 95% CI 1.05-1.85, p=0.02), likely because of inferior post-relapse OS in this cohort (HR 1.82, 95% CI 1.27-2.61, P = .001). DLBCL was the major cause of death in both cohorts (62% versus 59%). Older patients should not be denied auto-HCT solely on the basis of chronological age.

Bispecific targeting of CD20 and CD19 increases polyfunctionality of chimeric antigen receptor T-cell products in B-cell malignancies.

BACKGROUND AIMS: Selective immune pressure contributes to relapse due to target antigen downregulation in patients treated with anti-CD19 chimeric antigen receptor (CAR) T cells. Bispecific lentiviral anti-CD20/anti-CD19 (LV20.19) CAR T cells may prevent progression/relapse due to antigen escape. Highly polyfunctional T cells within a CAR T-cell product have been associated with response in single-antigen-targeted anti-CD19 CAR T cells. METHODS: The authors performed a single-cell proteomic analysis to assess polyfunctional cells in our LV20.19 CAR T-cell product. Analysis was limited to those treated at a fixed dose of 2.5 × 106 cells/kg (n = 16). Unused pre-infusion CAR T cells were thawed, sorted into CD4/CD8 subsets and stimulated with K562 cells transduced to express CD19 or CD20. Single-cell production of 32 individual analytes was measured and polyfunctionality and polyfunctional strength index (PSI) were calculated. RESULTS: Fifteen patients had adequate leftover cells for analysis upon stimulation with CD19, and nine patients had adequate leftover cells for analysis upon stimulation with CD20. For LV20.19 CAR T cells, PSI was 866-1109 and polyfunctionality was 40-45%, which were higher than previously reported values for other CAR T-cell products. CONCLUSIONS: Stimulation with either CD19 or CD20 antigens resulted in similar levels of analyte activation, suggesting that this product may have efficacy in CD19- patient populations.

Mimicking Myelodysplastic Syndrome: Importance of Differential Diagnosis.

Copper deficiency is a rare nutritional deficiency with hematological manifestations that mimic those found in myelodysplastic syndrome, a hematological malignancy incurable without allogeneic hematopoietic stem cell transplantation. Bone marrow biopsy findings and peripheral blood counts are oftentimes insufficient to differentiate the two conditions. Moreover, the symptoms of copper deficiency can arise years after the surgery, making diagnosis a challenge. In patients with new-onset pancytopenia, copper deficiency must be considered on the differential, especially in the setting of known risk factors such as bariatric surgery, zinc supplementation, and celiac disease. Herein, we present a case of a 61-year-old female with a remote history of gastric bypass being evaluated for MDS in the context of progressive pancytopenia and new-onset paresthesias. The patient was found to have low serum copper and ceruloplasmin. Copper supplementation largely resolved the hematological abnormalities, but the limb paresthesias remain. This case highlights the need to identify copper deficiency early and distinguish it from MDS in order to prevent permanent neurological deficits and catastrophic response should the patient undergo hematopoietic stem cell transplantation.

Manufacturing chimeric antigen receptor T cells from cryopreserved peripheral blood cells: time for a collect-and-freeze model?

BACKGROUND AIMS: Chimeric antigen receptor (CAR)-modified T-cell therapy has revolutionized outcomes for patients with relapsed/refractory B-cell malignancies. Despite the exciting results, several clinical and logistical challenges limit its wide applicability. First, the apheresis requirement restricts accessibility to institutions with the resources to collect and process peripheral blood mononuclear cells (PBMCs). Second, even when utilizing an apheresis product, failure to manufacture CAR T cells is a well-established problem in a significant subset. In heavily pre-treated patients, prior chemotherapy may impact T-cell quality and function, limiting the ability to manufacture a potent CAR T-cell product. Isolation and storage of T cells shortly after initial cancer diagnosis or earlier in life while an individual is still healthy are an alternative to using T cells from heavily pre-treated patients. The goal of this study was to determine if a CAR T-cell product could be manufactured from a small volume (50 mL) of healthy donor blood. METHODS: Collaborators at Cell Vault collected 50 mL of whole peripheral venous blood from three healthy donors. PBMCs were isolated, cryopreserved and shipped to the Medical College of Wisconsin. PBMCs for each individual donor were thawed, and CAR T cells were manufactured using an 8-day process on the CliniMACS Prodigy device with a CD19 lentiviral vector. RESULTS: Starting doses of enriched T-cell numbers ranged from 4.0 × 107 cells to 4.8 × 107 cells, with a CD4/CD8 purity of 74-79% and an average CD4:CD8 ratio of 1.4. On the day of harvest, total CD3 cells in the culture expanded to 3.6-4.6 × 109 cells, resulting in a 74- to 115-fold expansion, an average CD4:CD8 ratio of 2.9 and a CD3 frequency of greater than 99%. Resulting CD19 CAR expression varied from 19.2% to 48.1%, with corresponding final CD19+ CAR T-cell counts ranging from 7.82 × 108 cells to 2.21 × 109 cells. The final CAR T-cell products were phenotypically activated and non-exhausted and contained a differentiated population consisting of stem cell-like memory T cells. CONCLUSIONS: Overall, these data demonstrate the ability to successfully generate CAR T-cell products in just 8 days using cryopreserved healthy donor PBMCs isolated from only 50 mL of blood. Notably, numbers of CAR T cells were more than adequate for infusion of an 80-kg patient at dose levels used for products currently approved by the Food and Drug Administration. The authors offer proof of principle that cryopreservation of limited volumes of venous blood with an adequate starting T-cell count allows later successful manufacture of CAR T-cell therapy.

Bispecific Chimeric Antigen Receptor T Cell Therapy for B Cell Malignancies and Multiple Myeloma.

Chimeric antigen receptor (CAR) modified T cell therapy offers a targeted immunotherapeutic approach to patients with refractory hematological malignancies. This technology is most advanced in B cell malignancies and multiple myeloma and is rapidly evolving as more data become available regarding clinical efficacy and response durability. Despite excellent initial response rates with single antigen targeting CARs, failure to respond to therapy and relapse due to target antigen downregulation remain clinical challenges. To mitigate immunophenotypic selective pressures, simultaneous dual antigen targeting with bispecific CAR T cells or multiple administration of different populations of CAR T cells may prevent relapse by addressing one resistance mechanism attributed to antigenic loss. This article will review recently published data on the use of dual targeting with CAR T cells from early phase clinical trials aimed at treating B cell malignancies and multiple myeloma.

Infectious Diseases Consultation Is Associated With Decreased Mortality in Enterococcal Bloodstream Infections.

BACKGROUND: Enterococcus species frequently cause health care-associated bacteremia, with high attributable mortality. The benefit of consultation with infectious disease (ID) specialists has been previously illustrated with Staphylococcus aureus bacteremia. Whether ID consultation (IDC) improves mortality in enterococcal bacteremia is unknown. METHODS: This is a retrospective cohort single-center study from January 1, 2015, to June 30, 2016, that included all patients >18 years of age admitted with a first episode of Enterococcus bacteremia. Patients were excluded if death or transfer to palliative care occurred within 2 days of positive blood culture. RESULTS: Two hundred five patients were included in the study, of whom 64% received IDC. Participants who received IDC were more likely to undergo repeat cultures to ensure clearance (99% vs 74%; P < .001), echocardiography (79% vs 45%; P < .001), surgical intervention (20% vs 7%; P = 0.01), and have appropriate antibiotic duration (90% vs 46%; P < .001). Thirty-day mortality was significantly higher in the no-IDC group (27 % vs 12 %; P < .007). In multivariate analysis, 30-day in-hospital mortality was associated with both E. faecium bacteremia (adjusted odds ratio [aOR], 2.39; 95% confidence interval [CI], 1.09-5.23) and IDC (aOR, 0.35; 95% CI, 0.16-0.76). CONCLUSIONS: Patients who received IDC for Enterococcus bacteremia had significantly lower 30-day mortality. Further prospective studies are necessary to determine if these outcomes can be validated in other institutions for patients who receive IDC with Enterococcus bacteremia.

Outcomes of patients with limited-stage aggressive large B-cell lymphoma with high-risk cytogenetics.

There is a paucity of data regarding outcomes and response to standard therapy in patients with limited-stage (LS) agressive B-cell lymphoma (LS-ABCL) who harbor MYC rearrangement (MYC-R) with or without BCL2 and/or BCL6 rearrangements. We conducted a multicenter retrospective study of MYC-R LS-ABCL patients who received either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or more intensive immunochemotherapy (IIC) plus or minus consolidative involved-field radiation therapy (IFRT). One hundred four patients from 15 academic centers were included. Forty four patients (42%) received R-CHOP, of whom 52% had IFRT. Sixty patients (58%) received IIC, of whom 40% had IFRT. Overall response rate was 91% (84% complete response [CR]; 7% partial response). Patients with double-hit lymphoma (DHL; n = 40) had a lower CR rate compared with patients with MYC-R only (75% vs 98%; P = .003). CR rate was higher in the IFRT vs no-IFRT group (98% vs 72%; P < .001). Median follow-up was 3.2 years; 2-year progression-free survival (PFS) and overal survival (OS) were 78% and 86% for the entire cohort, and 74% and 81% for the DHL patients, respectively. PFS and OS were similar across treatment groups (IFRT vs no IFRT, R-CHOP vs IIC) in the entire cohort and in DHL patients. Our data provide a historical benchmark for MYC-R LS-ABCL and LS-DHL patients and show that outcomes for this population may be better than previously recognized. There was no benefit of using IIC over R-CHOP in patients with MYC-R LS-ABCL and LS-DHL.

The impact of structural factors on diagnostic delay in diffuse large B-cell lymphoma.

BACKGROUND: Reducing diagnostic delays in cancer has been a major interest worldwide; however, the literature on diagnostic delays in lymphoma remains scarce. Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma. We aimed to determine whether certain structural factors predicted diagnostic delays in DLBCL and whether diagnostic delays impacted overall survival (OS). METHODS: Data were extracted via a retrospective cohort design from a single academic tertiary care referral center. A total of 104 patients were included. Time from first symptoms to diagnosis of <3 months was defined as "early diagnosis" and ≥3 months as "delayed diagnosis". Analysis was performed with student's t-test, chi-square testing, binomial logistic regression, and Kaplan-Meier log-rank testing. RESULTS: "Delayed diagnosis" was more likely with lower stage, lower international prognostic index (IPI), and further distance from referral center (OR 0.66, CI 0.46-0.95; OR 0.69, CI 0.51-0.94; OR 1.008, CI 1.001-1.015). Patients of "other" ethnicity and without medical insurance were more likely to have significant diagnostic delays and worse overall survival (P = 0.002 and P = 0.007, respectively). Diagnostic delays of ≥3 months did not predict worse OS. However, delays of >6 months did predict worse OS. CONCLUSION: Our data suggest that excessive diagnostic delays of more than 6 months, ethnic minority status, and uninsured status in DLBCL may lead to worse outcomes. Efforts should be undertaken to reduce excessive diagnostic delays. More investigation needs to be done on the impacts of diagnostic delays in both DLBCL and other aggressive lymphomas.

Impact of Infectious Disease Consultation on Clinical Management and Mortality in Patients With Candidemia.

Candidemia has a high attributable mortality. The objective of this study was to determine the impact of infectious disease consultation on mortality and clinical outcomes in candidemia. Infectious disease consultation was associated with better adherence to guidelines and improved survival, even in patients with high Acute Physiology and Chronic Health Evaluation II scores.