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Background: Fludarabine-based chemoimmunotherapy with rituximab is frequently used in patients with indolent and mantle-cell lymphomas who relapse after alkylating chemotherapy. We aimed to compare the efficacy and safety of rituximab with bendamustine or fludarabine in patients with relapsed, indolent, non-Hodgkin lymphoma and mantle-cell lymphoma.Methods: For this randomised, non-inferiority, open-label, phase 3 trial, we recruited patients from 55 centres in Germany, who were subsequently randomised centrally according to prespecified randomisation lists with permuted blocks of randomly variable block size to rituximab (375 mg/m(2), day 1) plus either bendamustine (90 mg/m(2), days 1 and 2) or fludarabine (25 mg/m(2), days 1-3) every 28 days for a maximum of six 28-day cycles. Patients were aged 18 years or older with a WHO performance status of 0-2 and had relapsed or refractory indolent or mantle-cell lymphoma; patients refractory to regimens that included rituximab, bendamustine, or purine analogue drugs were excluded. Patients were stratified by histological subtypes of lymphoma and by their latest previous therapies. Treatment allocation was not masked. The primary endpoint was progression-free survival and the final analysis was completed per protocol. Non-inferiority of bendamustine plus rituximab versus fludarabine plus rituximab was defined as a difference of less than 15% in 1-year progression-free survival. The protocol was amended in July, 2006, after approval of rituximab maintenance (375 mg/m(2) every 3 months for up to 2 years), which was then given to patients achieving a response to either trial treatment. This study is registered with ClinicalTrials.gov, number NCT01456351 (closed to enrolment, follow-up is ongoing).Findings: Between Oct 8, 2003, and Aug 5, 2010, we randomly assigned 230 patients to treatment groups (116 bendamustine plus rituximab, 114 fludarabine plus rituximab). 11 patients were excluded for protocol violations and were not followed up further (two in the bendamustine plus rituximab group and nine in the fludarabine plus rituximab group). Thus, 219 patients were included in the per-protocol analysis (114 bendamustine plus rituximab, 105 fludarabine plus rituximab). 1-year progression-free survival with bendamustine plus rituximab was 0·76 (95% CI 0·68-0·84) and 0·48 (0·39-0·58) with fludarabine plus rituximab (non-inferiority p<0·0001). At a median follow-up of 96 months (IQR 73·2-112·9), median progression-free survival with bendamustine plus rituximab was 34·2 months (95% CI 23·5-52·7) and 11·7 months (8·0-16·1) with fludarabine plus rituximab (hazard ratio [HR] 0·54 [95% CI 0·38-0·72], log-rank test p<0·0001). Safety outcomes were similar in both groups, with 46 serious adverse events recorded (23 in the bendamustine plus rituximab group and 23 in the fludarabine plus rituximab group), most commonly myelosuppression and infections.Interpretation: In combination with rituximab, bendamustine was more effective than fludarabine, suggesting that bendamustine plus rituximab may be the preferred treatment option for patients with relapsed indolent and mantle-cell lymphomas.Funding: Roche Pharma AG, Ribosepharm GmbH, Mundipharma GmbH, Studiengruppe indolente Lymphome (StiL). [ABSTRACT FROM AUTHOR]

Summary: Background: Randomized controlled trials (RCTs) reported conflicting results on the impact of high-dose chemotherapy (HDCT) and autologous stem cell transplantation in the first-line treatment of patients with aggressive non-Hodgkin lymphoma (NHL). Methods: We performed a systematic meta-analysis to assess the efficacy HDCT compared to conventional chemotherapy in aggressive NHL patients with regard to complete response (CR), overall survival (OS), event-free survival (EFS), toxicity, and impact of the age-adjusted International Prognostic Index (aaIPI) risk factors. We searched the Cochrane Library, MEDLINE and other databases (1/1990 to 1/2005). Hazard ratio (HR), relative risks (RR) and 95% confidence intervals (CIs) were calculated using the fixed effect model. Results: Fifteen RCTs including 2728 patients were identified. HDCT improved CR when compared to conventional chemotherapy (RR 1.11, CI 1.04–1.18). Overall, there was no evidence for HDCT to improve OS (HR 1.05, 95% CI 0.92–1.19) or EFS (HR 0.92, 95% CI 0.80–1.05) when compared with conventional chemotherapy. However, subgroup analysis indicated OS differences (p =0.032) between good (HR 1.46, 95% CI 1.02–2.09) and poor risk (HR 0.95, 95% CI 0.81–1.11) patients. Conflicting results were reported for poor risk patients, where some studies reported improved and others reduced OS and EFS after HDCT. Conclusion: There was no evidence that HDCT improved OS and EFS in good risk NHL patients. The evidence for poor risk patients is inconclusive. HDCT should not be further investigated in good risk patients with aggressive NHL but high quality studies in poor risk patients are warranted. [Copyright &y& Elsevier]

Secondary central nervous system lymphoma (SCNSL) confers a dismal prognosis and treatment advances are constrained by the lack of prospective studies and real-world treatment evidence. Patients with SCNSL of all entities were included at first diagnosis and patient characteristics, treatment data, and outcomes were prospectively collected in the Secondary CNS Lymphoma Registry (SCNSL-R) (NCT05114330). 279 patients from 47 institutions were enrolled from 2011 to 2022 and 243 patients (median age: 66 years; range: 23–86) were available for analysis. Of those, 49 (20 %) patients presented with synchronous (cohort I) and 194 (80 %) with metachronous SCNSL (cohort II). The predominant histology was diffuse large B-cell lymphoma (DLBCL, 68 %). Median overall survival (OS) from diagnosis of CNS involvement was 17·2 months (95 % CI 12–27·5), with longer OS in cohort I (60·6 months, 95 % CI 45·5-not estimable (NE)) than cohort II (11·4 months, 95 % CI 7·8–17·7, log-rank test p < 0.0001). Predominant induction regimens included R-CHOP/high-dose MTX (cohort I) and high-dose MTX/cytarabine (cohort II). Rituximab was used in 166 (68 %) of B-cell lymphoma. Undergoing consolidating high-dose therapy and autologous hematopoietic stem cell transplantation (HDT-ASCT) in partial response (PR) or better was associated with longer OS (HR adjusted 0·47 (95 % CI 0·25–0·89), p = 0·0197). This study is the largest prospective cohort of SCNSL patients providing a comprehensive overview of an international real-world treatment landscape and outcomes. Prognosis was better in patients with SCNSL involvement at initial diagnosis (cohort I) and consolidating HDT-ASCT was associated with favorable outcome in patients with PR or better. • Large prospective study in SCNSL, including n = 243 patients diagnosed from 2011 to 2022. • Providing real-world data from an international registry. • Reporting patient characteristics, treatments and outcomes in SCNSL. • High-dose therapy followed by stem cell transplant is associated with better survival. [ABSTRACT FROM AUTHOR]