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Follicular lymphoma: 6-year follow-up of the RELEVANCE trial

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A recent study published in the Journal of Clinical Oncology shows that the drug combination lenalidomide + rituximab is a durable, effective and safe alternative to the standard regimen combining rituximab and chemotherapy to treat patients with advanced follicular lymphoma, previously untreated.

This clinical update1 of the RELEVANCE2 study, a phase 3 trial which showed that the combination of lenalidomide + rituximab (R2) was as effective at 120 weeks as the combination of rituximab + chemotherapy (R-chemo), reports long-term follow-up data on toxicity and efficacy of treatments.

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The authors point out that immunochemotherapy has remained the standard first-line treatment for patients with follicular lymphoma (FL).3 However, studies have shown that LF is also immunoresponsive to non-chemotherapeutic regimens.4-6

Lenalidomide, an immunomodulatory agent with multiple properties, including modification of cytokine production and stimulation of T cells and natural killer cells,7 has shown promising activity in combination with rituximab in the treatment of advanced FL.

Methodology in brief

From December 2011 to November 2014, a total of 1030 patients with grade 1-3 FL were randomized 1:1 to receive treatment R2 or R-chemo, followed by maintenance rituximab. R2 included 513 patients and R-chemo 517 distributed as follows, at the choice of the investigator: rituximab + cyclophosphamide, vincristine and prednisone = 28 patients; rituximab + bendamustine = 117 patients; rituximab + cyclophosphamide, doxorubicin, vincristine and prednisone = 372 patients.

Baseline characteristics were similar in both groups. Five hundred seven (99%) R2 patients and 503 (97%) R-chemo patients completed the full 120 weeks of treatment.

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Principle results

After a median follow-up of 72 months, progression-free survival was 60% and 59% for R2 and R-chemo respectively (hazard ratio: 1.03; 95% CI: 0.84–1.27).

Overall survival at six years was estimated at 89% in both groups. The overall response after progression was 61% and 59% in the R2 and R-chemo groups respectively.

The estimated five-year survival rate after progression was 69% and 74% in the R2 and R-chemo groups respectively.

Primary and secondary malignancies occurred in 11% and 13% of patients (p=0.34) in the R2 and R-chemo groups respectively. No new safety signal was observed.

In conclusion, both groups maintained very favorable results in terms of progression-free survival and overall survival at six years. Together, these data show that R2 and R-chemo produce similar durable responses in patients with follicular lymphoma. R2 therefore constitutes an acceptable, long-term alternative without chemotherapy.


  1. Morschhauser, F. et al. (2022). Six-year results from RELEVANCE: lenalidomide plus rituximab (R2) versus rituximab-chemotherapy followed by rituximab maintenance in untreated advanced follicular lymphoma. J Clin Oncol 40(28), 3239-3245.
  2. Morschhauser F. et al. (2018). Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med 379, 934-947.
  3. Flinn I.W. et al. (2019). First-line treatment of patients with indolent non-Hodgkin lymphoma or Mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: Results of the BRIGHT 5-year follow-up study. J Clin Oncol 37, 984-991.
  4. Ghielmini M. et al. (2004). Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood 103, 4416-4423.
  5. Hainsworth J.D. et al. (2005). Maximizing therapeutic benefit of rituximab: Maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma — A randomized phase II trial of the Minnie pearl cancer research network. J Clin Oncol 23, 1088-1095.
  6. Rohatiner A.Z. et al. (2005). Meta-analysis to evaluate the role of interferon in follicular lymphoma. J Clin Oncol 23, 2215-2223.
  7. Gandhi A.K. et al. (2014). Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.). Br J Haematol 164, 811-821.

This article has been translated from its original French and originally appeared on our sister site Profession Santé.

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