Tafasitamab combination linked to longer progression-free survival in investigational follicular lymphoma trial

Evidence before this study

To more fully understand the current treatment landscape and associated challenges in indolent non-Hodgkin lymphoma, we searched the PubMed database for articles published in English between Jan 1, 2020, and March 10, 2025, on the role of the tumour microenvironment as well as the impact of differences in CD20 expression in tumours on disease progression and development of treatment resistance. We used the search terms “((“non-Hodgkin lymphoma” OR “follicular lymphoma” OR “marginal zone lymphoma”) AND CD20) AND English [Language] AND (“2020/01/01”[Date - Publication]: “2025/03/10”[Date - Publication])”. Based on published reports from the search, the tumour microenvironment restricts host immune responses and treatment with anti-CD20 therapy (eg, rituximab) might reduce CD20 expression on tumour cells, contributing to resistance or relapse after monoclonal antibody therapy. Further, prognosis generally worsens with each subsequent therapy in patients with relapsed or refractory disease, highlighting the need for the development of additional treatment options that could further improve survival outcomes. Tafasitamab is an Fc-enhanced humanised monoclonal antibody that was designed to target the broadly expressed B-cell antigen CD19. In preclinical studies in models of diffuse large B-cell lymphoma and Burkitt lymphoma, antitumour activity was increased compared with respective monotherapy treatments when tafasitamab was combined with rituximab and different chemotherapeutic and non-chemotherapeutic drugs, including lenalidomide. Tafasitamab is currently approved in the USA, the EU, and other countries in combination with lenalidomide for the treatment of adult patients with relapsed or refractory, diffuse, large B-cell lymphoma who are not eligible for autologous stem cell transplantation.

Added value of this study

In a follicular lymphoma patient population with high burden of disease, including many who were refractory to anti-CD20 monoclonal antibody therapy, tafasitamab in combination with lenalidomide and rituximab was associated with significantly longer progression-free survival compared with placebo added to lenalidomide and rituximab. This improvement was seen in all subgroups analysed (including in patients with disease progression or relapse within 24 months of initial diagnosis status, anti-CD20-refractory status, and by number of previous lines of therapy). Additionally, tafasitamab was associated with higher rates of overall response and metabolic complete response versus placebo. The safety profile of this combination was consistent with expectations and manageable for this population, and, importantly, the addition of tafasitamab did not compromise lenalidomide or rituximab delivery. To our knowledge, our study is the first to validate the approach of combining two unconjugated monoclonal antibodies (anti-CD19 with anti-CD20) in treatment of lymphoma in a large, phase 3, randomised clinical trial.

Implications of all the available evidence

CD19 represents a potential treatment target for patients with relapsed or refractory follicular lymphoma following anti-CD20 therapy. Data from our study demonstrate promising results of the addition of tafasitamab to lenalidomide and rituximab. Because this combination can be administered in the community as well as tertiary centres, these encouraging results indicate that it might become a new option for standard-of-care treatment for patients with relapsed or refractory follicular lymphoma, particularly as a second-line treatment for which few options are currently available. Future analyses will yield robust data on overall survival, as well as a more in-depth examination of quality of life in patients treated with tafasitamab. Additionally, analyses of CD19 expression in patients following treatment with tafasitamab will provide information to help guide subsequent treatment decisions.

Source: The Lancet