Modern therapeutic approaches in the treatment of relapsed and refractory marginal zone lymphoma

Abstract

Marginal zone lymphomas (MZL) are a group of indolent B-cell lymphomas originating from B-lymphocytes of the marginal zone of lymphoid follicles of lymph nodes, spleen, or extranodal tissues. The group includes five distinct clinical entities, which together represent the third most common group of non-Hodgkin lymphomas in Czech Republic. In recent years, there has been a significant broadening of treatment options beyond conventional immunochemotherapy for relapsed refractory (R/R) disease.

In the MAGNIFY Phase IIIb multicenter study, the combination of lenalidomide and rituximab followed by rituximab maintenance therapy in 76 patients with R/R MZL after failure of ≥ 1 prior line of therapy.achieved an overall response rate (ORR) of 64 % (49/76), complete remission (CR) in 39 % (30/76), and a median progression-free survival (PFS) of 41.2 months.

Bruton's tyrosine kinase inhibitors, particularly zanubrutinib, have significantly expanded the treatment options for R/R disease. In the MAGNOLIA phase II, zanubrutinib led to an ORR of 68.2 % (45/66) and CR of 25.8 % (17/66) in patients who had received at least one prior line of anti-CD20 therapy. The two-year estimated PFS) was 70.9 %, and the toxicity profile was favorable.

Therapy with T lymphocytes with chimeric antigen receptors also appears highly promising, particularly the liso-cel, which achieved an ORR of 95.5 % (63/66), a CR of 62.1 % (41/66) and an estimated 2year PFS of 85.7 % in R/R patients with a median of 3 previous lines of treatment in the TRANSCEND FL trial.

Data on the efficacy and safety of bispecific antibodies in MZL is currently limited, with relatively the most information available on odronextamab. In the phase II ELM-2 trial, odronextamab monotherapy led to an ORR and CR of 79.3 % (23/29) in patients after ≥ 2 lines of systemic therapy.