Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma. Results of the HD2002 prospective multicentre randomized phase III trial

Witzens-Harig, Mathias; Benner, Axel; McClanahan, Fabienne; Klemmer, Jennifer; Brandt, Julia; Brants, Elke; Rieger, Michael A.; Meißner, Julia; Hensel, Manfred; Neben, Kai; Dreger, Peter; Lengfelder, Eva; Schmidt‐Wolf, Ingo G.H.; Krämer, Alwin; Ho, Anthony D.

doi:10.1111/bjh.13652

Cited by 32 publications

(45 citation statements)

References 25 publications

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“…Male patients had better outcomes while female patients did not. Harig et al[11] came to a similar conclusion and also found there was no gender difference in EFS in the maintenance group. We performed a subgroup analysis of the latter two trials using a random-effect model [Fig 5].…”

Section: Resultsmentioning

confidence: 65%

“…Four trials including 1325 patients were analyzed with three reporting EFS[9, 10, 12] and one reporting RFS[11]. There was no obvious heterogeneity with I 2 = 0.0% (p = 0.703).…”

Section: Resultsmentioning

confidence: 99%

“…Riihijarvi et al[25] reported female patients had better PFS. However, Harig[11] and Jaeger[12] posed a challenge to this result. They argued that EFS was significantly improved in male patients but not in female patients.…”

Section: Discussionmentioning

confidence: 99%

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Rituximab maintenance therapy for patients with diffuse large B-cell lymphoma: A meta-analysis

Zhou

Zhang

et al. 2017

PLoS ONE

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PurposeThe addition of rituximab to standard chemotherapy has significantly improved survival in patients with lymphoma. Recently, maintenance therapy with rituximab has been shown to prevent relapse and provide survival benefits for patients with follicular or mantle cell lymphoma. However, the effects of rituximab in patients with diffuse large B-cell lymphoma (DLBCL) remain unclear. Two new studies involving rituximab in the treatment of DLBCL were performed this past year. We performed a meta analysis to evaluate the effects of rituximab maintenance treatment of patients with DLBCL.MethodsSeveral databases (PubMed, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) databases were reviewed for relevant randomized controlled trials published prior to May, 2016. Two reviewers assessed the quality of the included studies and extracted data independently. The hazard ratios (HRs) for time-to-event data and relative risks (RRs) for the other data were pooled and estimated.ResultsTotally 5 studies including 1740 patients were eligible for the meta-analysis. Compared to the observation group, patients who received rituximab maintenance therapy had significantly improved event-free survival (EFS) (HR = 0.80, 95% CI: 0.65–0.98) and progression-free survival (PFS) (HR = 0.72, 95% CI: 0.54–0.94). However, there was no statistically significant difference in overall survival (OS) (HR = 0.66, 95% CI: 0.27–1.29). A subgroup analysis suggested that male patients may benefit from rituximab maintenance therapy with a better EFS (HR = 0.53, 95% CI: 0.34–0.82-), while this advantage was not observed in female patients (HR = 0.99, 95% CI: 0.64–1.52).ConclusionsRituximab maintenance may provide survival benefits beyond that afforded by first- and second-line chemotherapy alone, especially in male patients. However, maintenance rituximab treatment may cause more adverse events. It is recommended that both survival benefits and adverse events should be taken into consideration when making treatment decisions.

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Section: Resultsmentioning

confidence: 65%

“…Four trials including 1325 patients were analyzed with three reporting EFS[9, 10, 12] and one reporting RFS[11]. There was no obvious heterogeneity with I 2 = 0.0% (p = 0.703).…”

Section: Resultsmentioning

confidence: 99%

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Rituximab maintenance therapy for patients with diffuse large B-cell lymphoma: A meta-analysis

Zhou

Zhang

et al. 2017

PLoS ONE

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“…Recently, rituximab maintenance therapy (375 mg/m 2 every 3 months for 2 years) was shown to improve survival in male patients with DLBCL [21]. To the best of our knowledge, rituximab maintenance therapy has not been evaluated in PMBCL patients so far.…”

Section: Resultsmentioning

confidence: 99%

Addition of rituximab to CHOP-like chemotherapy in first line treatment of primary mediastinal B-cell lymphoma

et al. 2017

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BackgroundThe addition of rituximab (R) to CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) -like therapy has improved survival in primary mediastinal B-cell lymphoma (PMBCL) patients. However, these results were obtained in young low risk patients and a reevaluation in an unselected patient cohort is warranted.MethodsIn this study, we analyzed 80 PMBCL patients treated with a CHOP-based regimen with and without rituximab.ResultsIn the non-rituximab cohort 10-year progression free survival (PFS) was 67% and 10-year overall survival (OS) was 72% versus a PFS of 95% and a OS of 92% in the rituximab group, PFS P = 0.001, OS P = 0.023. A subgroup PFS analysis by international prognostic index (IPI) risk revealed that all risk groups benefit from addition of rituximab to induction chemotherapy. In addition, OS probability was higher in the group of non-low risk patients who were treated with rituximab compared to those patients who did not receive rituximab (P = 0.035). In multivariate analysis, only addition of rituximab to induction chemotherapy and reaching complete remission (CR) after first line therapy had a beneficial effect on both PFS and OS, whereas IPI, age, upfront high dose (HD) chemotherapy/autologous blood stem cell transplantation (ABSCT) and rituximab maintenance had no impact on survival.ConclusionsOur data demonstrate a survival benefit in unselected PMBCL patients treated with CHOP-like induction regimen and additional rituximab independently of the IPI risk score.

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“…Prolonged rituximab administration was adopted by several studies in de novo DLBCL patients in the first remission (reviewed in Table 5) (Jaeger et al, 2015, Witzens-Harig et al, 2015, Huang et al, 2012, Habermann et al, 2006). Instead of rituximab maintenance up to three years, we applied rituximab consolidation with two additional doses on patients' intention when CR was achieved.…”

Section: Discussionmentioning

confidence: 99%

B-cell Function Gene Mutations in Diffuse Large B-cell Lymphoma: A Retrospective Cohort Study

Zhong

Huang

et al. 2017

EBioMedicine

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Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous subtype of non-Hodgkin lymphoma. In addition to clinical and immunophenotypic characteristics, recurrent gene mutations have recently been identified in patients with DLBCL using next-generation sequencing technologies. The aim of this study is to investigate the clinical relevance of B-cell function gene mutations in DLBCL. Clinical analysis was performed on 680 Chinese DLBCL patients (146 non-CR and 534 CR cases) treated with six cycles of 21-day R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), alone or followed by two additional doses of rituximab consolidation on patients' own intention. Somatic mutations of B-cell function genes were further screened on 275 (71 non-CR and 204 CR) cases with available tumor samples by targeted sequencing, including genes involved in B-cell receptors (BCRs) pathway (CARD11, LYN, CD79A, and CD79B), Toll-like receptors (TLRs) pathway (MYD88), and tumor necrotic factor receptor (TNFR) pathway (TRAF2 and TNFAIP3). B-cell function gene mutations occurred in 44.0% (121/275) of DLBCL patients. The TLRs and TNFR related gene mutations were more frequently observed in non-CR patients (p = 0.019 and p = 0.032, respectively). BCRs related gene mutations, as well as revised IPI (R-IPI) and double BCL-2/MYC expression, were independently related to short progression-free survival in DLBCL after CR. The adverse prognostic effect of BCRs related gene mutations could be overcome by two additional doses of rituximab consolidation. These results highlight the molecular heterogeneity of DLBCL and identify a significant role of B-cell function gene mutations on lymphoma progression and response to rituximab in DLBCL.

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Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma. Results of the HD2002 prospective multicentre randomized phase III trial

Cited by 32 publications

References 25 publications

Rituximab maintenance therapy for patients with diffuse large B-cell lymphoma: A meta-analysis

Rituximab maintenance therapy for patients with diffuse large B-cell lymphoma: A meta-analysis

Addition of rituximab to CHOP-like chemotherapy in first line treatment of primary mediastinal B-cell lymphoma

B-cell Function Gene Mutations in Diffuse Large B-cell Lymphoma: A Retrospective Cohort Study

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