In the phase II L-MIND trial reported in The Lancet Oncology, Gilles Salles, MD, and colleagues found that the combination of the Fc-enhanced anti-CD19 monoclonal antibody tafasitamab plus lenalidomide produced responses in patients with relapsed or refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation.

Gilles Salles, MD

The Fc region of an antibody mediates serum half-life and effector functions, and engineering the Fc region allows the generation of molecules that are better suited to particular activities. The Fc modification of tafasitamab is intended to potentiate antibody-dependent cell-mediated cytotoxicity and cellular phagocytosis, thus aiming to improve tumor cell killing.

Preclinical data suggested potential synergistic activity with the combination of tafasitamab and lenalidomide.

Study Details

In the trial, 81 patients enrolled from sites in 10 countries between January 2016 and November 2017 received tafasitamab plus lenalidomide at 25 mg/d for up to twelve 28-day cycles, followed by tafasitamab monotherapy in patients with stable disease or better until disease progression. Tafasitamab was given at 12 mg/kg weekly on days 1, 8, 15, and 22 of cycles 1 to 3 (with an additional loading dose on day 4 of cycle 1) and on days 1 and 15 of subsequent cycles.

Patients had to have relapsed or refractory measureable disease after treatment with one to three systemic regimens, including at least one anti-CD20 therapy. The primary endpoint was the proportion of patients with objective response on independent review committee assessment.

Responses

Median follow-up was 13.2 months. A total of 28 patients (35%) were receiving tafasitamab monotherapy at data cutoff. Among 80 patients who received at least one dose of both agents, objective response was observed in 48 (60%), with complete response observed in 34 (43%).

Median duration of response was 21.7 months, with 72% of responders having response lasting ≥ 12 months. Among patients with complete response, median response duration was not reached, with 93% having response lasting ≥ 12 months. At a median follow-up of 17.3 months for progression-free survival, median progression-free survival was 12.1 months.

Adverse Events

The most common grade ≥ 3 adverse events among all 81 patients were neutropenia (48%), thrombocytopenia (17%), and febrile neutropenia (12%). Serious adverse events occurred in 51% of patients, with the most common being pneumonia (6%), febrile neutropenia (6%), pulmonary embolism (4%), bronchitis (2%), atrial fibrillation (2%), and congestive cardiac failure (2%). Adverse events led to discontinuation of one or both drugs in 25% of patients. Adverse events of special interest occurred in seven patients (9%), including tumor flares in three (grades 1, 2, and 3), allergic dermatitis in three (all grade 3), and grade 2 basal cell carcinoma in one.

The investigators concluded, “Tafasitamab in combination with lenalidomide was well tolerated and resulted in a high proportion of patients with relapsed or refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation having a complete response, and might represent a new therapeutic option in this setting.”

Dr. Salles, of Hospices Civils de Lyon, Hôpital Lyon-Sud, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by MorphoSys. For full disclosures of the study authors, visit thelancet.com.