Association of race/ethnicity and insurance with survival in patients with diffuse large B-cell lymphoma in a large real-world cohort.

The large real-world EHR dataset Flatiron has shown that race was not significantly associated with poorer survival in patients with DLBCL. Medicaid insurance status was significantly associated with poorer overall survival and time to second-line therapy or death due to any cause in patients with DLBCL aged <65 years.

OBJECTIVE: Few studies have evaluated disparities in race, ethnicity, and health insurance in real­world health outcomes for patients with diffuse large B­cell lymphoma (DLBCL). This study aimed to evaluate association between racial disparities and health insurance with real­world health outcomes. METHODS: Patients with DLBCL (January 2011­July 2021) treated with first­line therapy were selected from a real­world database. Variables of interest included race/ethnicity, health insurance type (Medicaid, Commercial) by patient age (<65, ≥65 years), stage at diagnosis, overall survival (OS), and time to second­line therapy or death due to any cause (TTNTD). RESULTS: Among 5362 patients with DLBCL (82% White, 7% Black, 8% Hispanic/Latino, 3% Asian), White patients were older (mean age, 66.7 vs. 59.3­62.5 years) and less likely to have Medicaid insurance (1.7% vs. 3.4%­5.9%). Adjusted hazard ratios (aHR) for OS (Black, 0.88 [95% confidence interval, 0.72­1.07]; Hispanic/Latino, 0.84 [0.70­1.03]; Asian, 0.82 [0.59­1.16]) and TTNTD (Black, 0.89 [0.75­1.05]; Hispanic/Latino, 0.85 [0.73­1.00]; Asian, 1.11 [0.86­1.43]) were similar to those of White patients. Among patients aged <65 years, Medicaid­insured versus Commercially insured patients had more advanced disease (stage III­IV, 66% vs. 48%), worse OS (aHR, 0.52 [0.34­0.80]; p = 0.003), and shorter TTNTD (aHR, 0.70 [0.49­0.99]; p = 0.044). CONCLUSIONS: There was no statistically significant difference in these variables/outcomes between Medicaid­insured and commercially insured patients aged ≥65 years. Medicaid­insured status was significantly associated with poorer OS and TTNTD in patients with DLBCL aged <65 years but not in those aged ≥65 years, with or without adjusting for other baseline characteristics. Race was not significantly associated with these outcomes.

The impact of race and ethnicity on diffuse large B-cell lymphoma outcomes within the veterans health administration (VHA).

We performed a retrospective chart review of 6266 randomly selected DLBCL patients treated in the VHA nationwide between 1/1/2011 and 12/31/2021. The 3178 patients who met inclusion criteria were predominantly male (97%) and white (75%). Median age of diagnosis for Black patients was 63 years vs 69 years for the entire cohort (p < 0.001). However, patients in each race/ethnicity subgroup presented with similar rates of stage I/II and III/IV disease, IPI score, cell of origin and HIT status. Outcomes analysis revealed similar treatment, response rates, median overall survival, and 1-, 3-, and 5-year survival across all subgroups. Hispanic patients had a 21% lower risk of death (HR = 0.79) than white patients, and Black patients had no significant difference in survival (HR = 0.98). This large retrospective study shows that when standard of care therapy is given within an equal access system, short-term treatment and survival outcomes are the same for all races.

Impact of Race and Age and their Interaction on Survival Outcomes in Patients With Diffuse Large B-Cell Lymphoma.

BACKGROUND: Advances in treatment for patients with Diffuse Large B-Cell Lymphoma (DLBCL) have led to improved patient outcomes but the magnitude of these disparities remains understudied with regards to improved survival outcomes. We sought to describe changes in DLBCL survival trends over time and explore potential differential survival patterns by patients' race/ethnicity and age. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with DLBCL from 1980 to 009 and determined 5-year survival outcomes for all patients, categorizing patients by year of diagnosis. We used descriptive statistics and logistic regression, adjusting for stage and year of diagnosis, to describe changes in 5-year survival rates over time by race/ethnicity and age. RESULTS: We identified 43,564 patients with DLBCL eligible for this study. Median age was 67 years (ages: 18-64 = 44.2%, 65-79 = 37.1%, 80 + = 18.7%). Most patients were male (53.4%) and had advanced stage III/IV disease (40.0%). Most patients were White race (81.4%), followed by Asian/Pacific Islander (API) (6.3%), Black (6.3%), Hispanic (5.4%), and American Indian/Alaska Native (AIAN) (0.05%). Overall, the 5-year survival rate improved from 35.1% in 1980 to 52.4% in 2009 across all races and age groups (odds ratio [OR] for 5-year survival with increasing year of diagnosis = 1.05, P < .001). Patients in racial/ethnic minority groups (API: OR = 0.86, P < .0001; Black: OR = 0.57, P < .0001; AIAN: OR = 0.51, P = .008; Hispanic: 0.76, P = 0.291) and older adults (ages 65-79: OR = 0.43, P < .0001; ages 80+: OR = 0.13, P < .0001) had lower 5-year survival rates after adjusting for race, age, stage, and diagnosis year. We found consistent improvement in the odds of 5-year survival for year of diagnosis across all race and ethnicity groups (White: OR = 1.05, P < .001; API: OR = 1.04, P < .001; Black: OR = 1.06, p<.001; AIAN: OR = 1.05, P < .001; Hispanic: OR = 1.05, P < .005) and age groups (ages 18-64: OR = 1.06, P < .001; ages 65-79: OR = 1.04, P < .001; ages 80+: OR = 1.04, P < .001). CONCLUSION: Patients with DLBCL experienced improvements in 5-year survival rates from 1980 to 2009, despite persistently lower survival among patients in racial/ethnic minority groups and older adults.

Enrollment of Black Participants in Pivotal Clinical Trials Supporting US Food and Drug Administration Approval of Chimeric Antigen Receptor-T Cell Therapy for Hematological Malignant Neoplasms.

Importance: Disparities that affect Black persons with various hematological malignant neoplasms are substantial, yet little is known about disparities related to the use of US Food and Drug Administration (FDA)-approved chimeric antigen receptor-T cell (CAR-T) therapy. Objective: To examine the enrollment of Black participants in clinical trials that resulted in a subsequent FDA approval of CAR-T products in hematological malignant neoplasms. Design, Setting, and Participants: A cross-sectional study was performed using publicly available data on drug products and demographic subgroups from Drugs@fda in the period of August 2017 to May 2021. Data analysis included patients with large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, acute lymphoblastic leukemia, and multiple myeloma who were enrolled into 7 clinical trials that investigated various CAR-T products. The study was conducted from July 1, 2021, to November 30, 2021. Main Outcomes and Measures: Frequencies of participation of Black participants were calculated with adjustment for disease prevalence. Results: Of the 1057 enrolled patients included in the study, CAR-T products were given to 746 patients (71%), and efficacy was reported for 729 enrolled patients (69%) across all the approved CAR-T products and indications. Most patients (1015 patients [96%]) were enrolled in the US. Black participants were included in the racial category other in the study that supported tisagenlecleucel approval in acute lymphoblastic leukemia; otherwise, their enrollment was specified either in the study publication and/or the demographic subgroup information available under the FDA product labeling information. The number of Black participants who received the CAR-T product and had reported efficacy varied between studies (range, 1-12 participants [2%-5%]). Adjusted prevalence measures showed the lowest participation to prevalence ratio of 0.2 for multiple myeloma and 0.6 for large B cell lymphoma. Conclusions and Relevance: The findings of this study suggest that there are substantial disparities affecting Black patients across all approved CAR-T products used to treat hematological malignant neoplasms with otherwise limited effective treatment options. The study findings might aid policy discussions regarding the immediate need of regulations that enforce certain thresholds of Black patients' enrollment before granting FDA approval.

Associations between race and survival in pediatric patients with diffuse large B-cell lymphoma.

BACKGROUND: The purpose of this study was to examine the factors associated with disparities in overall survival (OS) by race in pediatric diffuse large B-cell lymphoma (DLBCL) patients. METHODS: We evaluated clinical features and survival among patients ≤21 years of age diagnosed with stage I-IV DLBCL from 2004 to 2014 from the National Cancer Database (NCDB) using a multivariable Cox proportional hazards model. RESULTS: Among 1386 pediatric patients with DLBCL, 1023 patients met eligibility criteria. In unadjusted analysis, Black patients had a significantly higher overall death rate than White patients (HRBlack vs. White 1.51; 95% CI: 1.02-2.23, p = 0.041). The survival disparity did not remain significant in adjusted analysis, though controlling for covariates had little effect on the magnitude of the disparity (HR 1.46; 95% CI 0.93-2.31, p = 0.103). In adjusted models, presence of B symptoms, receipt of chemotherapy, stage of disease, and Other insurance were significantly associated with OS. Specifically, patients with B symptoms and those with Other insurance were more likely to die than those without B symptoms or private insurance, respectively (HR 1.75; 95% CI 1.22-2.50, p = 0.002) and (HR 2.56; 95% CI, 1.39-4.73, p = 0.0027), patients who did not receive chemotherapy were three times more likely to die than those who received chemotherapy (HR 3.10; CI 1.80-5.35, p < 0.001), and patients who presented with earlier stage disease were less likely to die from their disease than those with stage IV disease (stages I-III HR 0.34, CI 0.18-0.64, p < 0.001; HR 0.50, CI 0.30-0.82, p = 0.006, HR 0.72, CI 0.43-1.13, p = 0.152, respectively). CONCLUSIONS: Our results suggest that racial disparities in survival may be mediated by clinical and treatment parameters.

Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

PURPOSE: The CD79b-targeted antibody-drug conjugate polatuzumab vedotin (pola), alone and with chemoimmunotherapy, has clinical efficacy and a tolerable safety profile in B-cell non-Hodgkin lymphoma (B-NHL). We assessed (a) whether exposure from global studies of pola is comparable to Asian patients, and (b) if the recommended pola dose is appropriate in Asian patients based on exposure. METHODS: The pharmacokinetics (PK) of pola in Asian and global populations was characterized for three analytes (antibody-conjugated monomethyl auristatin E (MMAE) [acMMAE], total antibody, and unconjugated MMAE) in five phase 1b/2 single-agent and combination studies in B-NHL patients (JO29138 [JAPICCTI-142580], DCS4968g [NCT01290549], GO27834 [NCT01691898], GO29044 [NCT01992653], and GO29365 [NCT02257567]). PK data were compared between Japanese phase 1 JO29138 (JAPICCTI-142580) and global phase 1 DCS4968g (NCT01290549) studies and between Asian and non-Asian patients in the randomized relapsed/refractory B-NHL cohorts of the phase 1b/2 study GO29365 (NCT02257567). A population PK (popPK) model was used to assess the effects of Asian race and region on acMMAE and unconjugated MMAE exposure. RESULTS: PK non-compartmental analysis (NCA) parameters for the key analyte acMMAE in the Japanese JO29138 (JAPICCTI-142580) and global phase 1 DCS4968g (NCT01290549) studies were similar. In GO29365 (NCT02257567), the phase 1b/2 combination study, mean exposure to the analytes was generally lower in Asian patients (by ~ 9.9 to 17.5%), but not to a clinically meaningful extent. Overall, the popPK model further suggested comparable PK in Asian patients with B-NHL (race or region) versus non-Asian patients. CONCLUSION: Race has no clinically meaningful effect on pola PK. These results (and observations from efficacy/safety exposure-response analyses) support no pola dose adjustments are warranted for Asian patients with DLBCL.

Mediation analyses of socioeconomic factors determining racial differences in the treatment of diffuse large B-cell lymphoma in a cohort of older adults.

Despite near universal health coverage under Medicare, racial disparities persist in the treatment of diffuse large B-cell lymphoma (DLBCL) among older patients in the United States. Studies evaluating DLBCL outcomes often treat socioeconomic status (SES) measures as confounders, potentially introducing biases when SES factors are mediators of disparities in cancer treatment.To examine differences in DLBCL treatment, we performed causal mediation analyses of SES measures, including: metropolitan statistical area (MSA) of residence; census-tract poverty level; and private Medicare supplementation using the Surveillance, Epidemiology and End Results-Medicare linked database between 2001 and 2011. In this retrospective cohort study of DLBCL patients ages 66+ years, we conducted a series of multivariable logistic regression analyses estimating odds ratios (OR) and 95% confidence intervals (CI) relating chemo- and/or immuno-therapy treatment and each SES measure, comparing non-Hispanic (NH)-black, Hispanic/Latino, and Asian/Pacific Islander (API) to NH-white patients.Compared to NH-white patients, racial/ethnic minority patients had lower odds of receiving chemo- and/or immuno-therapy treatment (NH-black: OR 0.84, 95% CI 0.65, 1.08; API: OR 0.80, 95% CI 0.64, 1.01; Hispanic/Latino: OR 0.78, 95% CI 0.64, 0.96) and higher odds of lacking private Medicare supplementation and residence within an urban MSA and poor census tracts. Adjustment for SES measures as confounders nullified observed racial differences. In causal mediation analyses, between 31% and 38% of race/ethnicity differences were mediated by having private Medicare supplementation.Providing equitable access to Medicare supplementation may reduce disparities in receipt of chemo- and/or immuno-therapy treatment in older DLBCL patients.

Diffuse large B-cell lymphoma in Southeast Asian cohort: expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy.

AIMS: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia. METHODS: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS). RESULTS: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTK high/LYN high) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05). CONCLUSIONS: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.

Safety and efficacy of obinutuzumab in Chinese patients with B-cell lymphomas: a secondary analysis of the GERSHWIN trial.

BACKGROUND: Patients with relapsed/refractory B-cell lymphomas have limited treatment options. GERSHWIN is an open-label, single-arm, phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically documented CD20+ relapsed/refractory chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL). The primary outcome measure of pharmacokinetics has been previously reported. We now present data on the secondary endpoint measures (e.g., safety, and efficacy and pharmacodynamics). METHODS: Patients received 1000 mg obinutuzumab intravenously on days 1, 8, and 15 of cycle 1 (CLL patients; first dose split over 2 days), and on day 1 of cycles 2-8. Each cycle lasted for 21 days; the treatment period was 24 weeks. All subjects receiving at least one dose of obinutuzumab were included in the analysis of safety, efficacy, as well as pharmacodynamics. RESULTS: A total of 48 patients (> 18 years of age) were enrolled (CLL: 12; DLBCL: 23; FL: 13). The subjects received a median of two lines of anticancer treatment prior to the enrollment. Thirty-five patients (72.9%) had at least one adverse event (AE). The most frequent AE was infusion-related reactions (15 patients; 31.3%), followed by pyrexia (11 patients; 22.9%). Treatment-related AEs were reported in 28 patients (58.3%), and included one death (interstitial lung disease). End-of-treatment (EoT) response rate was 33.3%. Best overall response rate was 47.9%. Most CLL patients achieved a partial response at EoT (58.3%). CD19+ depletion occurred in 75.0% of the patients with CLL, and all patients with FL and DLBCL. CONCLUSIONS: The safety and efficacy of obinutuzumab monotherapy in Chinese patients with B-cell lymphomas were similar to that observed in previous studies in non-Chinese patients; no new safety signals were observed. Clinical trial registration ID NCT01680991.

Ethnic variation in medical and lifestyle risk factors for B cell non-Hodgkin lymphoma: A case-control study among Israelis and Palestinians.

BACKGROUND: Risk factors for B-cell non-Hodgkin lymphoma (B-NHL) have not been assessed among Palestinian Arabs (PA) and Israeli Jews (IJ). METHODS: In a case-control study we investigated self-reported medical and lifestyle exposures, reporting odds ratios (ORs) and 95% confidence intervals [CIs], by ethnicity, for overall B-NHL and subtypes. RESULTS: We recruited 823 cases and 808 healthy controls. Among 307 PA/516 IJ B-NHL cases (mean age at diagnosis = 51 [±17] versus 60 [±15] years, respectively) subtype distributions differed, with diffuse large B-cell lymphoma (DLBCL) being prominent among PA (71%) compared to IJ (41%); follicular lymphoma (FL), was observed in 14% versus 28%, and marginal zone lymphoma, in 2% versus 14%, respectively. Overall B-NHL in both populations was associated with recreational sun exposure OR = 1.43 [CI:1.07-1.91], black hair-dye use OR = 1.70 [CI:1.00-2.87], hospitalization for infection OR = 1.68 [CI:1.34-2.11], and first-degree relative with hematopoietic cancer, OR = 1.69 [CI:1.16-2.48]. An inverse association was noted with alcohol use, OR = 0.46 [CI:0.34-0.62]. Subtype-specific exposures included smoking (FL, OR = 1.46 [CI:1.01-2.11]) and >monthly indoor pesticide use (DLBCL, OR = 2.01 [CI:1.35-3.00]). Associations observed for overall B-NHL in PA only included: gardening OR = 1.93 [CI:1.39-2.70]; history of herpes, mononucleosis, rubella, blood transfusion (OR>2.5, P<0.01 for all); while for IJ risk factors included growing fruits and vegetables, OR = 1.87 [CI:1.11-3.15]; and self-reported autoimmune diseases, OR = 1.99 [CI:1.34-2.95]. CONCLUSIONS: In these geographically proximate populations we found some unique risk factors for B-NHL. Heterogeneity in the observed associations by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by histology infer specific etiologic factors for lymphoma subtypes.

Associations between genetic variants in immunoregulatory genes and risk of non-Hodgkin lymphoma in a Chinese population.

We undertook a hospital-based case-control study to examine the associations between single nucleotide polymorphisms (SNPs) in selected immunoregulatory genes and non-Hodgkin lymphoma (NHL) risk in a Chinese population. One hundred and sixty-nine NHL patients diagnosed according to the World Health Organization (WHO) 2001 standard and 421 controls were recruited. Nine SNPs in three genes (IL-10, IL-1RN, and TNF-α) were selected based on predicted functions and previous study findings. Genetic association analysis was performed using the Cochran-Armitage trend test and multiple logistic regression. Four SNPs were associated with an increased risk of overall NHL: odds ratio per minor allele [ORper-minor-allele] and 95% confidence interval [CI] were 2.64 (1.75-3.98) for IL-10 rs1800893, 2.67 (1.72-4.16) for IL-1RN rs4251961, 1.80 (1.24-2.63) for TNF- α rs1800630, and 1.55 (1.02-2.37) for TNF- α rs2229094. These SNPs were also associated with an increased risk of diffuse large B-cell lymphoma (DLBCL). In addition, another SNP (TNF- α rs1041981) was associated with an increased risk of DLBCL (ORper-minor-allele=1.73, 95% CI 1.14-2.61). The findings provide evidence on the role of these immunoregulatory gene variants in NHL etiology.

Clinical Features of Systemic Metastatic Retinal Lymphoma in Japanese Patients.

PURPOSE: Systemic metastatic retinal lymphoma (SMRL) originates in systemic organs. It has been reported to exhibit clinical features similar to those of primary vitreoretinal lymphoma (PVRL). We report six cases of SMRL in a single-center survey in Japan. METHODS: The clinical and pathologic features in SMRL at the Kyushu University Hospital were retrospectively studied. RESULTS: The mean patient age at the onset of ocular involvement was 75.3 years. Four patients had brain involvement. The primary sites were: breast (2); chest (1); testis (1); intestinal tract (1); and nasal sinus (1). In all patients, the cytology of vitreous samples indicated diffuse large B-cell lymphoma (DLBCL). CONCLUSIONS: DLBCL is the most common subtype in our study. The prevalence of CNS involvement in patients with SMRL is similar to that with PVRL. The testis and breast may be common sites of origin for SMRL.

Racial patterns of patients with primary mediastinal large B-cell lymphoma: SEER analysis.

The aim of this study is to investigate the incidence and clinical outcomes of primary mediastinal large B-cell lymphoma (PMBL).Here we did a retrospective analysis using the surveillance, epidemiology, and end results (SEER) database to analyze the incidences and survival of patients with PMBL diagnosed during 2001-2012 among major ethnic groups.During 2001-2012, a total of 426 PMBL patients were identified, including 336 whites, 46 blacks, and 44 others. The incidence rates of female to male ratios in white, black, and other were 1.4938, 1.1202, and 1.7303 respectively, suggesting that the female-prominent disease occurrence was seen only in whites and others, but not in black population. Compared to white, the other had a worse 5-year overall survival (OS); however, factors including age, race, socioeconomic status, and stage associated with OS showed no significant difference among ethnic groups; thus, biology factors should be explored to explain the racial difference in OS.In conclusion, our findings revealed diversities in demographic features and prognosis among different racial groups.

Pathophysiological significance and therapeutic targeting of germinal center kinase in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, yet 40% to 50% of patients will eventually succumb to their disease, demonstrating a pressing need for novel therapeutic options. Gene expression profiling has identified messenger RNAs that lead to transformation, but critical events transforming cells are normally executed by kinases. Therefore, we hypothesized that previously unrecognized kinases may contribute to DLBCL pathogenesis. We performed the first comprehensive analysis of global kinase activity in DLBCL, to identify novel therapeutic targets, and discovered that germinal center kinase (GCK) was extensively activated. GCK RNA interference and small molecule inhibition induced cell-cycle arrest and apoptosis in DLBCL cell lines and primary tumors in vitro and decreased the tumor growth rate in vivo, resulting in a significantly extended lifespan of mice bearing DLBCL xenografts. GCK expression was also linked to adverse clinical outcome in a cohort of 151 primary DLBCL patients. These studies demonstrate, for the first time, that GCK is a molecular therapeutic target in DLBCL tumors and that inhibiting GCK may significantly extend DLBCL patient survival. Because the majority of DLBCL tumors (∼80%) exhibit activation of GCK, this therapy may be applicable to most patients.

MDR1 polymorphisms have an impact on the prognosis of Chinese diffuse large B cell lymphoma patients.

MDR1 (multidrug resistance 1) encodes an adenosine triphosphate (ATP)-dependent efflux transporter that plays a fundamental role in transportation of harmful compounds outside cells to maintain optimal health. The present study was aimed to investigate whether the MDR1 gene single nucleotide polymorphisms (SNPs) were associated with the prognosis of diffuse large B cell lymphoma (DLBCL). Three common SNPs, including C1236T, G2677T/A, and C3435T were focused on, and a total of 150 DLBCL patients from Jiangsu Han population were successively genotyped by polymerase chain reaction-allele-specific primers (PCR-ASP) method or DNA direct sequencing. At locus C1236T, patients carrying T allele (genotype CT and TT) had a prolonged overall survival (OS) when compared with patients with CC genotype (2-year OS 82.6 vs. 60.0 %, respectively; hazard ratio (HR) = 0.1, 95 % confidence interval (CI) 0.01-0.6, p = 0.016). At locus C3435T, complete remission/ complete remission unconfirmed (CR/CRu) rate in C allele group was significantly higher than T allele group (66.7 vs. 51.9 %, respectively; p = 0.009). The progression-free survival (PFS) curves of with T (genotype CT and TT) and without T (genotype CC) were significantly different (2-year PFS 46.4 % in with T group vs. 73.7 % in without T group, respectively; HR = 1.9, 95 % CI 1.0-3.6, p = 0.045). At locus G2677T/A, the age for genotypes AG and AT groups was significantly younger than the other genotypes (51.1 ± 12.6 vs. 57.7 ± 13.4 years, respectively; p = 0.033). In the haplotype analysis of loci 1236-3435, compared with T-C group, the C-T group displayed an inferior PFS rate (2-year PFS 23.0 vs. 50.6 %, respectively; HR = 7.8, 95 % CI 1.9-32.6, p = 0.005), while C-C and T-T groups showed an intermediate PFS rate. Our findings demonstrate that genotype CT + TT at locus C1236T, allele C, and genotype CC at locus C3435T might contribute to a relatively superior prognosis in DLBCL, as well as haplotype of T-C in loci 1236-3435. Besides, genotypes at locus G2677T/A might affect age at diagnosis, which has important prognostic value for DLBCL.

Improved Survival With Radiation Therapy in Stage I-II Primary Mediastinal B Cell Lymphoma: A Surveillance, Epidemiology, and End Results Database Analysis.

BACKGROUND: Primary mediastinal B cell lymphoma (PMBCL) is an uncommon lymphoma for which trials are few with small patient numbers. The role of radiation therapy (RT) after standard immunochemotherapy for early-stage disease has never been studied prospectively. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate PMBCL and the impact of RT on outcomes. METHODS AND MATERIALS: We queried the SEER database for patients with stage I-II PMBCL diagnosed from 2001 to 2011. Retrievable data included age, gender, race (white/nonwhite), stage, extranodal disease, year of diagnosis, and use of RT as a component of definitive therapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA) log-rank and multivariate (MVA) Cox proportional hazards regression analyses were performed. RESULTS: Two hundred fifty patients with stage I-II disease were identified, with a median follow-up time of 39 months (range, 3-125 months). The median age was 36 years (range, 18-89 years); 61% were female; 76% were white; 45% had stage I disease, 60% had extranodal disease, and 55% were given RT. The 5-year OS for the entire cohort was 86%. On UVA, OS was improved with RT (hazard ratio [HR] 0.446, P=.029) and decreased in association with nonwhite race (HR 2.70, P=.006). The 5-year OS was 79% (no RT) and 90% (RT). On MVA, white race and RT remained significantly associated with improved OS (P=.007 and .018, respectively). The use of RT decreased over time: 61% for the 67 patients whose disease was diagnosed from 2001 to 2005 and 53% in the 138 patients treated from 2006 to 2010. CONCLUSION: This retrospective population-based analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT. Nearly half of patients treated in the United States do not receive RT, and its use appears to be declining. In the absence of phase 3 data, the use of RT should be strongly considered for its survival benefit in early-stage disease.

Persistent Disparities Among Patients With T-Cell Non-Hodgkin Lymphomas and B-Cell Diffuse Large Cell Lymphomas Over 40 Years: A SEER Database Review.

BACKGROUND: As of 2013, more than 550,000 people are living with non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: We undertook a large Surveillance Epidemiology and End Results (SEER) based analysis to describe outcome disparities in different subgroups of aggressive T-cell and B-cell NHL patients, with a focus on various ethnicities. RESULTS: The final analysis included 7662 patients with T-cell and 84,910 with B-cell NHL. Survival analysis revealed that male sex and increasing age were independent predictors of worse overall survival (OS; P < .001). For aggressive T-cell NHL, there was no significant improvement in median OS between 1973 and 2011 (P = .081), and ethnic minorities (Asians, Hispanics, and African Americans) had significantly worse OS than whites (P < .001). There were similar trends for age, sex, and race for diffuse large B-cell NHL, but a significant improvement in median OS was seen over time (P < .001). CONCLUSION: These results are the first to elicit outcomes in a broad classification of ethnic minorities and underscore the urgency for development of novel therapeutics, especially in T-cell NHL. In addition, in-depth studies of disease biology and health care utilization are required for better triage of health care resources, especially for ethnic minorities.

MYC or BCL2 copy number aberration is a strong predictor of outcome in patients with diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL). Patients with DLBCL harboring MYC aberrations concurrent with BCL2 or/and BCL6 aberrations constitute a specific group with extremely poor outcome. In this study, we retrospectively investigated the incidence and prognosis of MYC, BCL2, and BCL6 aberrations with DLBCL patients in Chinese population. We applied fluorescence in situ hybridization and immunohistochemical analysis in 246 DLBCL patients. The results showed that patients with MYC or BCL2 copy number aberration (CNA) had significantly worse overall survival (OS) and progression-free survival (PFS) than negative cases (P < 0.0001). Patients with both MYC and BCL2 CNA had similar outcomes to those with classic double hit lymphoma or protein double expression lymphoma (MYC and BCL2/BCL6 coexpression). By multivariate analysis, MYC CNA, BCL2 CNA and double CNA were the independent worse prognostic factors. In conclusions, patients with MYC or BCL2 CNA constituted a unique group with extremely poor outcome and may require more aggressive treatment regimens.

Primary Bone Lymphoma: A Clinical Analysis of 17 Patients in a Single Institution.

Primary bone lymphoma (PBL) comprises less than 1% of all malignant lymphomas. Because few studies of PBL have been conducted in Japan, the characteristics of Japanese patients with PBL have not been fully elucidated. We retrospectively analyzed 17 patients diagnosed with PBL at our institution between 2001 and 2011. Median patient age was 60 years. Eleven patients had diffuse large B-cell lymphoma and 2 patients had T-cell lymphoma histology. The spine was the most frequently involved site at the time of presentation. There were 11 patients with stage IV disease and 11 patients with high or high-intermediate risk according to the International Prognostic Index (IPI). Thirteen patients achieved complete response (CR) after initial treatment. At a median follow-up of 31 months, the 3-year overall survival (OS) and progression free survival were 63.5 and 49.9%, respectively. Localized disease, low or low-intermediate IPI, and CR after initial treatment were associated with a good outcome in patients with PBL and significantly associated with a better OS. Spine involvement and T/NK-cell phenotype are more frequent in Japanese than in Caucasian patients with PBL.

Racial differences in three major NHL subtypes: descriptive epidemiology.

BACKGROUND: NHL (non-Hodgkin lymphoma) consists of over 60 subtypes, ranging from slow-growing to very aggressive. The three largest subtypes are DLBCL (diffuse large B-cell lymphoma), FL (follicular lymphoma), and CLL/SLL (chronic lymphocytic leukemia/small lymphocytic lymphoma). For each subtype, different racial groups have different presentations, etiologies, and prognosis patterns. METHODS: SEER (Surveillance, Epidemiology, and End Results) data on DLBCL, FL, and CLL/SLL patients diagnosed between 1992 and 2010 were analyzed. Racial groups studied included NHW (non-Hispanic whites), HW (Hispanic whites), blacks, and API (Asians and Pacific Islanders). Patient characteristics, age-adjusted incidence rate, and survival were compared across races. Stratification and multivariate analysis were conducted. RESULTS: There are significant racial differences for patients' characteristics, including gender, age at diagnosis, stage, lymph site, and age, and the patterns vary across subtypes. NHWs have the highest incidence rates for all three subtypes, followed by HWs (DLBCL and FL) and blacks (CLL/SLL). The dependence of the incidence rate on age and gender varies across subtypes. For all three subtypes, NHWs have the highest five-year relative survival rates, followed by HWs. When stratified by stage, racial difference is significant in multiple multivariate Cox regression analyses. CONCLUSIONS: Racial differences exist among DLBCL, FL, and CLL/SLL patients in the U.S. in terms of characteristics, incidence, and survival. The patterns vary across subtypes. More data collection and analysis are needed to more comprehensively describe and interpret the across-race and subtype differences.