Rituximab Maintenance in NHLs – Mini Review

Author: Sujeet Kumar   @sujeethemat

Rituximab is given as maintenance therapy in NHLs, although benefits of maintenance rituximab (MR) are still unclear for many NHLs and regimens and durations are confusing. My attempt to simplify this is here.


[1] If in stage I and II you have used R monotherapy (4 weekly doses x 4 doses) in low tumor burden or elderly patients then consolidate with R every 8 weeks for 4 doses. [NCCN]

[2] If R-Chemo has been given in stage II, III and IV then R maintenance can be given every 8-12 weeks x 12 doses [NCCN], every 8 weeks for 12 doses [ESMO].

    • FDA approval based on PRIMA study reporting significant benefit to PFS, but not OS]

[3] In relapse/refractory setting after 2nd line therapy R maintenance is to be given every 12 weeks for 2 years (8 doses) [NCCN]


[1] After aggressive therapy [ie R-DHAP, R-DHAP/R-CHOP Alternate, NORDIC regimen, R-Hyper CVAD] followed by HDCT + ASCT >> Maintenance R is to be given every 8 weeks x 3 years (18 doses).

    • [NCCN, ESMO, Evidence by LYSA group N Engl J Med (2017) MCL clinical trial reporting PFS as well as OS benefit]

[2] After less aggressive therapy in elderly with R-CHOP or R-BENDA in transplant ineligible >> R every 8 weeks until progression or toxicity [NCCN, ESMO, Evidence for R maintenance following R-CHOP from MCL Elderly Trial]

Note: No benefit of R Maintenance could be documented in MAINTAIN study post R-Benda in MCL patients. Multiple studies reported increased infection episodes with R Maintenance post R-Benda.


[1] Maintenance with rituximab (every 2 months for 1–2 years) may improve PFS but no OS advantage has been shown to date and maintenance may not be superior to retreatment on demand. Rituximab usually remains active at relapse. [ESMO – R maintenance not recommended in these]

[2] R maintenance [every 12 weeks x 2 years] only in those patients who were treated with single agent rituximab. [NCCN]


No role of rituximab maintenance in DLBCL


    • (A) NHL13 trial reported (2015) no EFS benefit (primary end point) with R maintenance however in subgroup analysis Men with low IPI benefitted most
    • (B) HOVON-Nordic LG trial also showed rituximab maintenance therapy does not prolong disease-free survival, and they could not identify a clinical subgroup that benefited as in NHL 13 trail.


Best possible Evidence base to recommend R Maintenance:

    • Lancet 2018: CLL 2007 SA Phase 3 Trial >> 2-year maintenance rituximab (500 mg/m2 every 8 weeks x 2 year) in selected elderly patients (65 years or older with chronic lymphocytic leukemia without del(17p)) improves progression-free survival (59% vs 49%) and shows an acceptable safety profile.

NOTE that similar finding were seen in AGMT CLL-8a Mabtenance randomized trial with 375 mg/m2 every 3 months for 2 year and published in Lancet 2016.

So the guidelines:-

[1] NCCN: 2020: No mention of Rituximab Maintenance in guidelines.

[2] ESMO: (2015 Guideline): Maintenance therapy in CLL patients with higher risk of relapse may have some benefit, but cannot be generally recommended.


NO Prospective data till now (One trial going on for this is a trial by German STiL group). Based on retrospective data ESMO and NCCN has differing opinion as given below. Will go with NCCN till prospective data is available.

[1] As per NCCN: Consider maintenance in WM patients achieving CR or are in VGPR/PR and are asymptomatic. [Evidence: Treon et al Br J Haematol 2011 reported significant improvement in both OS and PFS with R maintenance] Schedule R every 12 weeks x 2 years (8 doses).

[2] As per ESMO (2018): Although maintenance treatment with rituximab could provide some clinical benefit according to retrospective data, maintenance therapy cannot be recommended in WM due to the lack of prospective data.

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