Is Maintenance Therapy Necessary for Diffuse Large B-Cell Lymphoma Patients? Evaluating the Evidence
Understanding Maintenance Therapy in DLBCL: What You Need to Know
Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma. After initial treatment with regimens like R-CHOP, many patients achieve complete remission. This raises an important clinical question: should these patients undergo maintenance therapy to prolong remission and improve long-term outcomes?
Despite theoretical benefits, current evidence suggests that maintenance therapy—particularly with agents like rituximab or lenalidomide—does not significantly extend overall survival in DLBCL patients who have responded well to first-line treatment. While such therapies may delay disease progression, they do not ultimately increase life expectancy. Given the added costs, potential side effects, and lack of survival benefit, routine maintenance therapy is generally not recommended for this patient population.
Clinical Evidence Against Routine Maintenance Use
Rituximab Maintenance: Delayed Relapse Without Survival Gain
A multicenter randomized trial evaluated rituximab as a maintenance strategy in 415 adults over the age of 60 who achieved complete response following either R-CHOP or CHOP chemotherapy. Patients were assigned to receive either rituximab maintenance or observation only. At the three-year mark, those receiving rituximab showed improved progression-free survival (53% vs. 46%) compared to the control group.
However, no significant difference was observed in overall survival between the two groups. Further analysis revealed that the progression-free survival benefit was largely confined to patients who had originally been treated with CHOP alone, rather than the more effective R-CHOP regimen. Long-term follow-up data, presented in abstract form, confirmed that prolonged rituximab use did not translate into a survival advantage.
This indicates that while rituximab may temporarily suppress disease recurrence, it fails to alter the ultimate course of the illness in most DLBCL cases when used as maintenance.
Lenalidomide Maintenance: Modest PFS Improvement at a Cost
Another pivotal study involved 650 elderly patients (aged 60–80) with DLBCL who had achieved either complete or partial remission after R-CHOP therapy. These individuals were randomly assigned to receive either lenalidomide or placebo as maintenance treatment.
After three years of follow-up, lenalidomide demonstrated a statistically significant improvement in progression-free survival (hazard ratio: 0.7; 95% CI: 0.54–0.93), suggesting a moderate ability to delay relapse. However, by the 52-month mark, there was still no measurable improvement in overall survival.
More concerning were the increased toxicities associated with lenalidomide. Grade 3 and 4 neutropenia occurred in 56% of patients on lenalidomide versus only 22% in the placebo group. Skin-related adverse events were also more frequent (5% vs. 1%). These findings highlight a critical trade-off: modest gains in disease control come at the expense of higher toxicity and reduced quality of life, without extending life expectancy.
Why Some Clinics Still Use Maintenance Therapy
Despite strong evidence from high-quality trials published as early as 2017 in journals like Journal of Clinical Oncology, some medical centers—particularly in certain regions—continue to prescribe lenalidomide or rituximab as maintenance, even after autologous stem cell transplantation.
This practice may stem from misinterpretation of progression-free survival benefits as meaningful clinical improvements, or from reliance on outdated guidelines. In some cases, financial incentives or regional prescribing habits may play a role. However, leading international oncology organizations emphasize that delaying relapse without improving overall survival does not justify routine maintenance use, especially when weighed against drug costs and toxicity profiles.
Toward Evidence-Based Practice in DLBCL Management
The bottom line is clear: For patients with diffuse large B-cell lymphoma who respond well to standard induction therapy, maintenance strategies with rituximab or lenalidomide offer limited value. They may push back the time to relapse slightly, but they do not help patients live longer.
Given the absence of overall survival benefit and the presence of notable side effects, maintenance therapy should not be part of standard care outside of clinical trials. Instead, resources should focus on refining risk stratification, identifying high-risk subgroups who might benefit from novel approaches, and developing next-generation immunotherapies or targeted treatments.
Patients are encouraged to discuss their individual prognosis and treatment plan with hematologists familiar with current international guidelines. Staying informed about evidence-based practices ensures better decision-making and avoids unnecessary interventions that add burden without benefit.