Standard of care for patients with symptomatic, advanced-stage follicular lymphoma (FL) is rituximab-containing chemoimmunotherapy followed by rituximab maintenance. This prospective, multicenter, noninterventional study analyzed how efficacy and safety data from randomized controlled trials translate into clinical practice in Germany. Both treatment-naïve and relapsed/refractory patients with FL, who responded to rituximab-containing induction and were scheduled for rituximab maintenance, were observed for 24 months. Effectiveness was measured by response and Kaplan-Meier survival analysis. In addition, treatment patterns of induction and maintenance, as well as adverse events, were documented. The evaluable study population consisted of 310 first-line patients and 173 relapsed/refractory patients, including 116 patients with initial Ann-Arbor stage I/II and 20 patients with FL grade 3B. Regarding first-line induction, a shift from R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) to R-bendamustine was observed over time, as well as a decline in radiotherapy. 2-year progression-free survival rates were 88.3% (95% confidence interval [CI] 84.0-92.6) for first-line patients and 76.0% (95% CI: 68.8-83.3) for relapsed/refractory patients. Conversion from partial to complete remission (PR, CR) occurred in 53.4% of analyzed first-line patients with PR, resulting in 69.4% CRs at study end (relapsed/refractory: conversion in 42.9%, final CRs 57.9%). Safety results were consistent with the known safety profile of rituximab in this setting. Both treatment-naïve and relapsed/refractory patients with FL show favorable 2-year PFS rates and improvements in the remission status with postinduction rituximab monotherapy as maintenance and consolidation therapy.

Treatment of Burkitt lymphoma (BL) with intensive, multi-agent chemotherapy with aggressive central nervous system (CNS) prophylaxis results in high cure rates, although no regimen is standard of care. We examined population-based survival outcomes of adults with BL treated with a modified combination of cyclophosphamide, vincristine, doxorubicin, prednisone and systemic high-dose methotrexate (MTX) (CODOX-M) with IVAC (ifosfamide, mesna, etoposide, cytarabine and intrathecal MTX) (CODOX-M/IVAC) ± rituximab over a 15-year period in British Columbia. For the 81 patients identified (including 8 with CNS involvement and 18 with human immunodeficiency virus-associated BL), 5-year progression-free survival (PFS) and overall survival (OS) were 75% [95% confidence interval (CI): 63-83%] and 77% (95% CI: 66-85%), respectively, with no treatment-related deaths. Those who completed the regimen per protocol (n = 38) had significantly improved 5-year PFS 86% (P = 0·04) and OS 92% (P = 0·008), as did those under 60 years with 5-year PFS 82% (P = 0·005) and OS 86% (P = 0·002), which remained significant in multivariate analysis [PFS: hazard ratio (HR) 3·36, P = 0·018; OS HR 4·03, P = 0·012]. Incorporation of high-dose systemic methotrexate also significantly affected multivariate survival outcomes (OS HR 0·28, P = 0·025). Stem cell transplant in first remission had no effect on OS or PFS. This large, real-world analysis of BL patients treated with CODOX-M/IVAC ± rituximab demonstrates excellent survival outcomes comparable to clinical trials. These results help to serve as a benchmark when comparing curative therapies for BL patients as novel regimens are incorporated into clinical practice.

Background The neutrophil-to-lymphocyte ratio (NLR) has been known to predict the prognosis in diffuse large B-cell lymphoma (DLBCL). We planned to design a new prognostic model in DLBCL using well-known prognostic index and NLR. Methods The data of 232 DLBCL patients treated with first-line R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) from 2004 to 2017 were retrospectively reviewed. Patients with NLR ≥6 and <6 were determined as the high and low NLR groups, respectively. Treatment response and survival were compared according to NLR status. Nomograms for predicting 5-year progression-free survival (PFS) and overall survival (OS) rates were constructed using NLR and other prognostic factors based on the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) NCCN-IPI. Results The high NLR group had a low complete response (CR) rate compared to low NLR group (51.6% vs. 83.5%; p<0.001). The 5-year PFS and OS rates were 27.4% and 30% in the high NLR group and 61.1% and 63.7% in the low NLR group, respectively (both p<0.001). Multivariate analyses confirmed that NLR is one of the independent risk factors for failure to achieve CR and for worse PFS and OS. The nomogram showed superior discrimination ability for predicting 5-year PFS and OS rates compared with NCCN-IPI (c index 0.78 vs. 0.75 and 0.79 vs. 0.75, respectively). Conclusions High NLR was associated with poor treatment response and worse PFS and OS in DLBCL. The nomogram developed from NCCN-IPI-based variables and NLR may help the clinicians to predict the prognosis individually in DLBCL patients, although it needs to be validated in the independent cohort.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype characterized by both biological and clinical heterogeneity. In refractory cases, complete response/complete response unconfirmed rates in salvage therapy remain low. We performed whole-exome sequencing of DLBCL in a discovery cohort comprising 26 good and nine poor prognosis cases. After candidate genes were identified, prognoses were examined in 85 individuals in the DLBCL validation cohort. In the discovery cohort, five patients in the poor prognosis group harbored both a TP53 mutation and 17p deletion. Sixteen mutations were identified in OSBPL10 in nine patients in the good prognosis group, but none in the poor prognosis group. In the validation cohort, TP53 mutations and TP53 deletions were confirmed to be poor prognostic factors for overall survival (OS) (P = 0.016) and progression-free survival (PFS) (P = 0.023) only when both aberrations co-existed. OSBPL10 mutations were validated as prognostic markers for excellent OS (P = 0.037) and PFS (P = 0.041). Significant differences in OS and PFS were observed when patients were stratified into three groups-OSBPL10 mutation (best prognosis), the coexistence of both TP53 mutation and TP53 deletion (poorest prognosis), and others. In this study, the presence of both TP53 mutation and 17p/TP53 deletion, but not the individual variants, was associated with poor prognosis in DLBCL patients after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or similar regimens. We also identified OSBPL10 mutation as a marker for patients with excellent prognosis in the R-CHOP era.

Purpose: The value of 18F-fluorodeoxyglucose positron emission tomography /computed tomography (18F-FDG PET/CT) in assessing bone marrow involvement (BMI) of lymphoma remains controversial. The present study aims to evaluate the prognostic meaning of bone marrow FDG uptake pattern in PET/CT of newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients. Materials and Methods: 193 newly diagnosed DLBCL patients were retrospectively analyzed. All patients received 6-8 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). The type of BM FDG uptake pattern was recorded by two blinded reviewers independently. The relationship between clinicopathologic features and BM patterns was analyzed. The prognostic value of different BM patterns was evaluated by Log-rank test and Cox-regression analysis. Results: Out of 193 patients, 28 (15%) patients had focal BM FDG uptake higher than liver (fPET+), 18 (9%) patients showed diffuse BM uptake higher than liver (dPET+) and 147 (76%) patients had normal BM uptake (lower than liver) (nPET). BMB positive was found in 35.7% (10/28) of fPET+ patients, in 16.7% (3/18) of dPET+ patients and in 0.7% (1/147) of nPET patients. Diffuse BM pattern was associated with lower hemoglobin level and a trend of higher erythrocyte sedimentation rate (ESR). dPET+ patients had similar 3y-progression-free survival (3y-PFS) and 3y-overall survival (3y-OS) compared with nPET patients (80.5% vs 81.5%, p=0.701; 94.1% vs 90.6%, p=0.809, respectively), while fPET+ patients had worse 3y-PFS and 3y-OS compared with fPET- patients (32.7% vs 81.4%, p<0.001; 69.4% vs 90.9%, p=0.003, respectively). Multivariate analysis showed fPET+ (HR=2.270, p=0.025) and stage III/IV (HR=4.909, p=0.026) were independent predictors for PFS, but no factors were independently predictive for OS. Conclusion: PET/CT-directed BM patterns are meaningful in predicting prognosis of newly diagnosed DLBCL patients. Focal BM pattern is an independent predictor for PFS.

ER-negative breast cancer includes most aggressive subtypes of breast cancer such as triple negative (TN) breast cancer. Excluded from hormonal and targeted therapies effectively used for other subtypes of breast cancer, standard chemotherapy is one of the primary treatment options for these patients. However, as ER- patients have shown highly heterogeneous responses to different chemotherapies, it has been difficult to select most beneficial chemotherapy treatments for them. In this study, we have simultaneously developed single drug biomarker models for four standard chemotherapy agents: paclitaxel (T), 5-fluorouracil (F), doxorubicin (A) and cyclophosphamide (C) to predict responses and survival of ER- breast cancer patients treated with combination chemotherapies. We then flexibly combined these individual drug biomarkers for predicting patient outcomes of two independent cohorts of ER- breast cancer patients who were treated with different drug combinations of neoadjuvant chemotherapy. These individual and combined drug biomarker models significantly predicted chemotherapy response for 197 ER- patients in the Hatzis cohort (AUC = 0.637, P = 0.002) and 69 ER- patients in the Hess cohort (AUC = 0.635, P = 0.056). The prediction was also significant for the TN subgroup of both cohorts (AUC = 0.60, 0.72, P = 0.043, 0.009). In survival analysis, our predicted responder patients showed significantly improved survival with a >17 months longer median PFS than the predicted non-responder patients for both ER- and TN subgroups (log-rank test P-value = 0.018 and 0.044). This flexible prediction capability based on single drug biomarkers may allow us to even select new drug combinations most beneficial to individual patients with ER- breast cancer.