Modern approaches to the treatment of relapsed follicular lymphoma

Follicular lymphoma is a tumor of mature B-lymphocytes, characterized by a predominantly indolent course. Despite advances in first-line therapy, disease relapses still occur, and with an increase in the follow-up period, the risk of transformation into diffuse large B-cell lymphoma also increases. The choice of a further anticancer therapy is based on the results of a comprehensive examination and repeated biopsy. In addition, previous remission duration, previous treatment, clinical manifestation of relapse, the patient's somatic condition and comorbidity are taken into account.  A clinical observation of a 57-year-old patient with relapsed follicular lymphoma, who received various chemotherapy regimens in combination with rituximab in the 1st and subsequent lines, is presented. After repeated biopsy and exclusion of transformation into diffuse large B-cell lymphoma, the patient received lenalidomide therapy in combination with obinutuzumab. A partial antitumor response after 4 cycles with decrease in tumor volume by more than 80 % by the end of induction was achieved. The absence of severe adverse events, together with a pronounced antitumor effect, significantly improved the patient's quality of life.

1. Matasar M.J., Luminari S., Baar P.M. et al. Follicular lymphoma: recent and emerging therapies, treatment strategies, and remaining unmet needs. Oncologist 2019;24(11):1-15. DOI: 10.1634/theoncologist.2019-0138

2. Babicheva L.G., Tumian G.S., Osmanov E.A. et al. Follicular lymphoma. Clinical guidelines. Sovremennaya onkologiya = Journal of Modern Oncology 2020;22(2):34-51. (In Russ.). DOI: 10.26442/18151434.2020.2.200131

3. Follicular Lymphoma. NCCN Clinical Practice Guidelines in Oncology. Version 2.2022.

4. Niederfellner G., Lammens A., Mundigl O. et al. Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies. Blood 2011;118(2):358-67. DOI: 10.1182/blood-2010-09-305847

5. GAZYVA full Prescribing Information. South San Francisco, CA: Genentech USA, Inc., 2016.

6. Golay J., Da Roit F., Bologna L. et al. Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab. Blood 2013;122(20):3482-91. DOI: 10.1182/blood-2013-05-504043

7. Cheson B.D., Chua N., Mayer J. et al. Overall survival benefit in patients with rituximabrefractory indolent nonHodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIn study. J Clin Oncol 2018;36(22):2259-66. DOI: 10.1200/JCO.2017.76.3656

8. Radford J., Davies A., Cartron G. et al. Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). Blood 2013;122(7):1137-43. DOI: 10.1182/blood-2013-01-481341

9. Salles G., Morschhauser F., Solal-Celigny P. et al. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIn study. J Clin Oncol 2013;31(23):2920-6. DOI: 10.1200/JCO.2012.46.9718

10. Dave S.S., Wright G., Tan B. et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 2004;351(21):2159-69. DOI: 10.1056/NEJMoa041869

11. Morschhauser F., Le Gouill S., Feugier P. et al. Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. Lancet Haematol 2019;6(8):e429-37. DOI: 10.1016/S2352-3026(19)30089-4

12. Leonard J.P., Jung S.H., Johnson J. et al. Randomized trial of lenalidomide alone versus lenalidomide plus rituximab in patients with recurrent follicular lymphoma: CALGB 50401 (alliance). J Clin Oncol 2015;33(31):3635-40. DOI: 10.1200/JCO.2014.59.9258

13. Gribben J.G., Fowler N., Morschhauser F. Mechanisms of action of lenalidomide in B-cell nonHodgkin lymphoma. J Clin Oncol 2015;33(25):2803-11. DOI: 10.1200/JCO.2014.59.5363

14. Mossner E., Brunker P., Moser S. et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 2010;115(22):4393-402. DOI: 10.1182/blood-2009-06-225979

15. Link B.K., Maurer M.J., Nowakowski G.S. et al. Rates and outcomes of follicular lymphoma transformation in the immunochemotherapy era: a report from the University of Iowa/MayoClinic Specialized Program of Research Excellence Molecular Epidemiology Resource. J Clin Oncol 2013;31(26):3272-8. DOI: 10.1200/JCO.2012.48.3990