How effective is the combination of tafasitamab and lenalidomide in treating R/R DLBCL?

The Lymphoma Hub was pleased to speak to Gilles Salles, Memorial Sloan Kettering Cancer Center, New York, US. We asked, How effective is the combination of tafasitamab and lenalidomide in treating R/R DLBCL?

In this interview, Salles shared an overview of the evolving treatment landscape for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The discussion focused on novel immunotherapy approaches, particularly the combination of tafasitamab and lenalidomide, and its role in clinical practice.

Key points

The need for new treatment strategies

While approximately 60–70% of patients with DLBCL achieve remission with first-line therapy, those with high-risk features, such as advanced-stage disease and high International Prognostic Index (IPI) scores, often relapse. Historically, treatment options for patients with R/R DLBCL relied on salvage chemotherapy followed by autologous stem cell transplantation. However, new targeted therapies are reshaping the treatment paradigm.

Tafasitamab and lenalidomide: A promising combination

Tafasitamab is an anti-CD19 monoclonal antibody engineered for improved antibody–dependent cellular cytotoxicity. Preclinical studies demonstrated its enhanced effect when combined with lenalidomide, leading to increased tumor cell killing through natural killer cells, T cells, and macrophages.

L-MIND trial^1,2

The phase II L-MIND (NCT02399085) trial evaluated tafasitamab plus lenalidomide in 81 patients with R/R DLBCL. The overall response rate was 60%, and the median progression-free survival and overall survival were ~1 year and ~2 years, respectively. Notably, patients who achieved a complete response experienced prolonged disease control, with some remaining relapse-free beyond 5 years.

Tolerability and practical considerations

While the tafasitamab plus lenalidomide regimen is generally well tolerated, dose adjustments for lenalidomide are often necessary due to hematologic toxicities (neutropenia, anemia, thrombocytopenia). Other side effects, such as rash and gastrointestinal symptoms, can be managed with supportive care. Importantly, this outpatient regimen offers a significant advantage over hospitalization-intensive therapies such as CAR T-cell therapy.

Real-world evidence and positioning in treatment

Real-world data from 180 patients treated in community settings corroborated clinical trial findings, with an ORR of 60–70%, depending on patient characteristics (published ORR, 73%).³ Based on these findings, tafasitamab plus lenalidomide is best suited for second-line treatment, particularly for patients who relapse after frontline therapy but are not ideal candidates for CAR T-cell therapy.

Future directions and treatment sequencing

While tafasitamab plus lenalidomide is a valuable option, emerging treatments, including bispecific antibodies and CD19-directed CAR T-cell therapy, are expanding therapeutic choices. The optimal sequencing of these therapies remains an ongoing discussion. Notably, tafasitamab-treated patients retain CD19 expression, preserving the potential for subsequent CAR T-cell therapy.

In summary, tafasitamab plus lenalidomide represents a well-tolerated and effective option for R/R DLBCL, particularly for patients who are not eligible for intensive therapies. With increasing real-world data and continued follow-up, its role in clinical practice continues to be refined.

This educational resource is independently supported by Incyte. All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource.