BACKGROUND: Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon type of aggressive B-cell non-Hodgkin lymphoma. PMBCL shares some clinical and biologic features with nodular sclerosis classic Hodgkin lymphoma (cHL). Central nervous system (CNS) relapse is exceedingly rare in cHL. Therefore, it may be expected that CNS relapse in PMBCL is also uncommon. Herein, we examined the incidence of CNS relapse in patients with PMBCL treated with standard chemoimmunotherapy.
METHODS: This retrospective single center analysis included 154 patients with newly diagnosed PMBCL seen at Mayo Clinic. The CNS relapse rate was calculated using a competing risk model, with death considered as a competing risk.
RESULTS: With a median follow-up of 39 months, 3 patients experienced CNS relapse, all associated with systemic relapse. The cumulative incidence of CNS relapse for the entire cohort was 1.43% (95% CI, 0.3%-4.6%) at 1 year and 2.21% (95% CI, 0.6%-5.8%) at both 2 and 5 years. For those who did not receive CNS prophylaxis (n = 131), the incidence was 0.85% (95% CI, 0.1%-4.2%) at 1 year and 1.80% (95% CI, 0.3%-5.8%) at both 2 and 5 years. All 3 patients who experienced CNS relapse had R-CHOP as frontline therapy; 2 patients did not receive any CNS prophylaxis, while 1 patient received intrathecal CNS prophylaxis.
CONCLUSIONS: The risk of CNS relapse in PMBCL appears to be very low after treatment with standard chemoimmunotherapy, suggesting routine CNS prophylaxis is not necessary.

This study aimed to establish a standard treatment for disseminated extranodal large B-cell lymphoma, including intravascular large B-cell lymphoma (DEN-LBCL/IVL), and to validate the clinical diagnostic criteria we proposed. Between 2006 and 2016, 22 patients were enrolled in a clinical trial conducted by the Hokuriku Hematology Oncology Study Group. The first cycle of chemotherapy consisted of dose-reduced cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with delayed administration of rituximab. From the second to the sixth cycle, patients received conventional rituximab and CHOP therapy. The primary endpoint was overall survival (OS), while the secondary endpoints included the complete response (CR) rate and time to treatment failure (TTF). The results showed a CR rate of 73%, a median OS of 65 months, and a median TTF of 45 months. These findings indicate that patients with DEN-LBCL/IVL were effectively treated with our new chemoimmunotherapy regimen. Our clinical diagnostic criteria are useful for identifying patients who require early intervention.

BACKGROUND: Metformin has been shown to have antitumor activity in different tumor types. In DLBCL (Diffuse large B cell lymphoma), using metformin with front-line chemotherapy & immunotherapy resulted in improved clinical outcomes.
OBJECTIVE: To assess the effectiveness of incorporating metformin into the standard initial treatment regimen of R-CHOP for patients with DLBCL. The evaluation metrics included response rate, toxicity, progression-free survival (PFS), and overall survival (OS).
METHODS: This prospective phase 2 trial included 100 adult patients with histopathological evidence of DLBCL, eligible for first-line treatment with R-CHOP, life expectancy of at least 6 months, and performance status (PS) ≤ 2. Patients were randomized to receive either metformin plus R-CHOP or R-CHOP alone.
RESULTS: Each group included 50 patients. The metformin arm had more females than the standard arm (p=0.016). Nausea was significantly higher in the test arm than the standard arm (p=0.008). Metformin group had higher rates of complete remission (CR) at the end of treatment (92% vs 74%; p=0.017), lower rates of relapse/progression (10% vs 36%; p=0.002), and lower rates of overall mortality (4% vs 20%; p=0.014). The mean disease-free survival (DFS) was 24.5 months in the metformin group versus 20.2 months in the control arm (p=0.023). Likewise, the mean progression-free survival (PFS) was 25.91 versus 19.81 months and the mean overall survival (OS) was 27.39 versus 23.8 months (p-values= 0.002, and 0.013 respectively). By multivariate analysis of response and relapse, the use of metformin was an independent prognostic factor of CR and relapse.
CONCLUSIONS: The addition of metformin to standard R-CHOP could improve clinical outcomes in patients with DLBCL with a tolerable safety profile.

Health-related quality of life (HRQoL) data are important indicators of health status in patients with lymphoma. The objective of this analysis was to assess the impact of treatment with Sandoz rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on HRQoL in treatment-naïve adult patients with diffuse large B-cell lymphoma (DLBCL) included in the prospective, real-world REFLECT study. REFLECT is the first prospective study to assess HRQoL in patients with DLBCL treated with a rituximab biosimilar. HRQoL was assessed via the patient-reported European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire at baseline, mid-treatment (month 3), end of treatment (month 6), and follow-up (months 9 and 12). Subgroup analyses were performed to evaluate the influence of baseline characteristics on HRQoL, and associations between baseline HRQoL and treatment response. HRQoL was assessed in 169 patients. Mean global health status score remained stable from baseline (54.8) to mid-treatment (month 3; 54.7), before steadily improving through to end of treatment (month 6; 61.4), and follow-up month 9 (64.9) and month 12 (68.8). Similar trends were observed across most functional and symptom subscales. Higher cognitive, physical, or role functioning, and less appetite loss, diarrhea, fatigue, or pain at baseline, were all associated with an improved likelihood of reaching a complete versus partial response at the end of treatment. Overall, these findings confirm the HRQoL benefits of R-CHOP therapy in treatment-naïve adult patients with DLBCL, and suggest that baseline HRQoL may be predictive of treatment response.

UNASSIGNED: There are multiple recently approved treatments and a lack of clear standard-of-care therapies for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). While total cost of care (TCC) by the number of lines of therapy (LoTs) has been evaluated, more recent cost estimates using real-world data are needed. This analysis assessed real-world TCC of R/R DLBCL therapies by LoT using the IQVIA PharMetrics Plus database (1 January 2015-31 December 2021), in US patients aged ≥18 years treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or an R-CHOP-like regimen as first-line therapy.
UNASSIGNED: Treatment costs and resources in the R/R setting were assessed by LoT. A sensitivity analysis identified any potential confounding of the results caused by the impact of the COVID-19 pandemic on healthcare utilization and costs. Overall, 310 patients receiving a second- or later-line treatment were included; baseline characteristics were similar across LoTs. Inpatient costs represented the highest percentage of total costs, followed by outpatient and pharmacy costs.
UNASSIGNED: Mean TCC per-patient-per-month generally increased by LoT ($40,604, $48,630, and $59,499 for second-, third- and fourth-line treatments, respectively). Costs were highest for fourth-line treatment for all healthcare resource utilization categories. Sensitivity analysis findings were consistent with the overall analysis, indicating results were not confounded by the COVID-19 pandemic.
UNASSIGNED: There was potential misclassification of LoT; claims data were processed through an algorithm, possibly introducing errors. A low number of patients met the inclusion criteria. Patients who switched insurance plans, had insurance terminated, or whose enrollment period met the end of data availability may have had truncated follow-up, potentially resulting in underestimated costs.
UNASSIGNED: Total healthcare costs increased with each additional LoT in the R/R DLBCL setting. Further improvements of first-line treatments that reduce the need for subsequent LoTs would potentially lessen the economic burden of DLBCL.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.

Adult intussusception is a rare diagnosis that can be caused by non-Hodgkin\'s diffuse large B-cell lymphoma (DLBCL). In this case report, we discuss a middle-aged man who presented with non-specific symptoms of intussusception and absence of classic B symptoms. He was found to have intussusception secondary to stage IIIE, CD20 positive DLBCL. The patient underwent small bowel resection with anastomosis, followed by 6 cycles of R-CHOP, which resulted in complete remission of his neoplasm. In reporting this case, we hope to further highlight the role of malignancy in intussusception and guidance on appropriate therapy.

Primary cutaneous diffuse large B-cell lymphomas (PCDLBCLs) represent approximately 10%-20% of primary cutaneous B-cell lymphomas. They present as nodules in the skin or as rapidly growing aggressive behavior tumors with a poor prognosis. In this article, we report a case of PCDLBCL presented with an aggressively enlarging skin lesion on the right cheek. This case was diagnosed based on clinicopathological features and characteristic immunohistochemical expression. During the 11-month follow-up period, the patient showed significant clinical improvement after undergoing rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, abbreviated as R-CHOP chemotherapy, without evidence of extracutaneous dissemination or disease relapse.

BACKGROUND: MYC/BCL2 double expression (DE) is associated with poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). This study aimed to determine whether the addition of DE to the National Comprehensive Cancer Network Internal Prognostic Index (NCCN-IPI) could improve the prediction of disease progression in patients with DLBCL treated with R-CHOP.
METHODS: This confirmatory prognostic factor study retrospectively recruited patients with newly diagnosed DLBCL between January 1, 2014, and January 31, 2018, at Ramathibodi Hospital (RA) and Thammasat University Hospital (TU). The follow-up period ended on July 1, 2022. Tumors expressing MYC ≥ 40% and BCL2 ≥ 50% were classified as DE. We calculated the hazard ratios (HR) for progression-free survival (PFS) from the date of diagnosis to refractory disease, relapse, or death. Discrimination of the 5-year prediction was based on Cox models using Harrell\'s concordance index (c-index).
RESULTS: A total of 111 patients had DE (39%), NCCN-IPI (8%), and disease progression (46%). The NCCN-IPI adjusted HR of DE was 1.6 (95% confidence interval [CI]: 0.9-2.8; P = 0.117). The baseline NCCN-IPI c-index was 0.63. Adding DE to the NCCN-IPI slightly increased Harrell\'s concordance index (c-index) to 0.66 (P = 0.119).
CONCLUSIONS: Adding DE to the NCCN-IPI may not improve the prognostic value to an acceptable level in resource-limited settings. Multiple independent confirmatory studies from a large cohort of lymphoma registries have provided additional evidence for the clinical utility of DE.

High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are known for their aggressive clinical course and so are the ones with MYC and BCL2 protein overexpression. The optimal therapy for these lymphomas remains to be elucidated. A retrospective analysis of all diffuse large B-cell lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements diagnosed between 2017 and 2021 at the Institute of Oncology Ljubljana, Slovenia, has been performed. Only patients with double-expressor lymphoma (DEL), double-hit lymphoma (DHL), or triple-hit lymphoma (THL) were included. Demographic and clinical parameters were assessed, as well as progression-free survival (PFS) and overall survival (OS). In total, 161 cases out of 309 (161/309; 52,1%) were classified as DEL. Sixteen patients had DHL, MYC/BCL2 rearrangement was observed in eleven patients, and MYC/BCL6 rearrangement was observed in five patients. Five patients were diagnosed with THL. Out of 154 patients (according to inclusion/exclusion criteria) included in further evaluation, one-hundred and thirty-five patients had double-expressor lymphoma (DEL), sixteen patients had DHL, and three patients had THL. In total, 169 patients were treated with R-CHOP, 10 with R-CHOP and intermediate-dose methotrexate, 19 with R-DA-EPOCH, and 16 with other regimens. The median follow-up was 22 months. The 5-year OS for the whole DEL group was 57.1% (95% CI 45.9-68.3%) and the 5-year PFS was 76.5% (95% CI 72.6-80.4%). The log-rank test disclosed no differences in survival between treatment groups (p = 0.712) while the high-risk international prognostic index (IPI) carried a significantly higher risk of death (HR 7.68, 95% CI 2.32-25.49, p = 0.001). The 5-year OS for DHL patients was 32.4% (95% CI 16.6-48.2%) while all three TH patients were deceased or lost to follow-up. Our analyses of real-life data disclose that the R-CHOP protocol with CNS prophylaxis is a successful and curative treatment for a substantial proportion of DEL patients.