Research in context
Evidence before this study
Rituximab in combination with six to eight cycles of CHOP chemotherapy (R-CHOP) has been established as standard treatment for diffuse large B-cell lymphoma. We searched PubMed with the search terms “lymphoma”, “DLBCL”, “trial”, and “rituximab”, in English, published between Jan 1, 2002, and Dec 4, 2019. Three randomised trials demonstrated that rituximab improved event-free, progression-free, and overall survival compared with CHOP chemotherapy alone, resulting in a halving of lymphoma-related deaths in these trials. Since then, many trials have failed to improve therapy, suggesting that a plateau of efficacy has been reached with R-CHOP, especially in the subgroup of patients with good prognosis. Prognosis of aggressive non-Hodgkin lymphoma can be established by the International Prognostic Index (IPI), using the clinical parameters of age, tumour stage, serum lactate dehydrogenase concentration, performance status, and number of involved extralymphatic sites. The IPI was established in the pre-rituximab era. Pooled analyses of prospective, randomised trials confirmed the validity of IPI for R-CHOP regimens as well. Patients younger than 60 years without risk factors such as stage III–IV disease, increased serum lactate dehydrogenase concentration, poor performance status, and bulky disease (defined as maximum lymphoma diameter ≥7·5 cm) had a 3-year progression-free survival of 95% (95% CI 90–99) and an overall survival of 98% (95–100), when treated with six cycles of R-CHOP or R-CHOP-like regimens in the MInT trial.
Added value of this study
To our knowledge, this study is the first phase 3 study in aggressive B-cell lymphoma since rituximab was introduced, which showed that the treatment paradigm of six cycles of R-CHOP can be changed. It demonstrates that CHOP chemotherapy can be safely reduced to four cycles in young patients (≤60 years) with no risk factor according to the age-adjusted IPI and no bulky disease. Given this excellent outcome, it appears that some patients might be overtreated with six to eight cycles of R-CHOP.
Implications of all the available evidence
We consider these results to be potentially practice changing. Based on the current data, four cycles of CHOP combined with six doses of rituximab are non-inferior to six cycles of CHOP combined with six doses of rituximab in young low-risk patients with aggressive B-cell lymphoma.