Tafasitamab Plus Lenalidomide Demonstrates Long-Term Efficacy in R/R DLBCL

Responses with the combination of tafasitamab (MOR208) and lenalidomide (Revlimid) followed by tafasitamab monotherapy appear to be long-lasting with tolerable toxicities in patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL), according to 2-year follow-up results from the phase 2 L-MIND study (NCT02399085) presented in a poster during the virtual 25th Congress of the European Hematology Association (EHA).

“These results, complimented with a favorable safety profile, indicate the utility of this novel immunological combination as a potential treatment option for patients with r/r DLBCL,” said Gilles Salles, MD, PhD, during the poster presentation.

Prior to the long-term data, the primary analysis of tafasitamab combined with lenalidomide demonstrated durable responses in patients with r/r DLBCL who were ineligible for autologous stem cell transplant. The best objective response rate (ORR) per investigator assessment was 60.0% (95% CI, 48.4%-70.8%). Among the patients who had a response to the combination, the median duration of response (DOR) was 21.7 months (95% CI, 21.7-not reached [NR]).

Out of 81 patients who were enrolled, 80 were included in the full efficacy analysis and all patients were included in the safety analysis. After at least 2 years of follow-up, 22 patients were still being treated with tafasitamab plus lenalidomide, while 59 patients had discontinued treatment. Thirty-eight of the discontinuations were a result of death, 14 patients were included in the survival follow-up, and 7 were lost to follow-up.

The ORR achieved after at least 2 years was 58.5%, per Independent Review Committee (IRC) assessment. The responses included complete responses (CRs) in 33 patients (41.3%) and partial responses (PRs) in 14 patients (17.5%). Also, 12 patients achieved stable disease (SD, 15.0%), while the remaining 8 patients had progressive disease (PD,10.0%).

The median DOR per IRC assessment was 34.6 months (95% CI, 26.1-34.6) in the overall population. Among patients who achieved a CR, the median DOR was NR (95% CI, 26.1 months-NR). For those who achieved a PR, the median DOR was 5.6 months (95% CI, 2.2-34.6%).

Objective response and DOR data were consistent with those observed in the primary analysis.

Survival was evaluated after 2 years and showed a median progression-free survival (PFS) of 16.2 months (95% CI, 6.3-NR) with a median follow-up of 22.6 months (95% CI, 22.2-27.4). The median overall survival (OS) after 2 years of follow-up was 31.6 months (95% CI, 18.3 months-NR).

The long-term safety data reveals that the combination of tafasitamab and lenalidomide is well tolerated in r/r DLBCL. In terms of grade 3 or higher hematologic treatment-emergent adverse events (TEAEs), the most frequent were neutropenia (49.4%), thrombocytopenia (17.3%), and febrile neutropenia (12.3%). Grade 3 or higher non-hematologic TEAEs were predominantly pneumonia and hypokalemia, occurring in 8.6% and 6.2% of patients, respectively.

Serious AEs were observed in less than 2% of patients, with the most common being pneumonia (8.6%), febrile neutropenia (6.2%), and pulmonary embolism (3.7%). Bronchitis, lower respiratory tract infection, atrial fibrillation, and congestive cardiac failure were also common, each occurring in 2.5% of patients.

There were 2 notable findings from the safety analysis regarding the overall toxicity burden. Specifically, of the most common TEAEs, neutropenia was observed at a rate of 1.14/per patient year (PY), thrombocytopenia was reported at 0.26/PY, and febrile neutropenia at 0.11/PY. Of the most frequent non-hematologic TEAEs, pneumonia was observed at a rate of 0.07/PY and hypokalemia was at 0.06/PY. The other notable finding was that the number and severity of TEAEs decreased once patients moved on to tafasitamab monotherapy after completing the combination treatment.

In the L-MIND study, patients received 12 mg/kg tafasitamab intravenously in 28-day cycles. The drug was administered once weekly during cycle 1 through 3 with a loading dose on day 4 of cycle 1, then the agent was administered every 2 weeks for the subsequent cycles. Lenalidomide at 25 mg was administered orally on days 1 through 21 of cycles 1 through 12. Following the final cycle of tafasitamab/lenalidomide, patients received tafasitamab monotherapy every 2 weeks until disease progression.

L-MIND is ongoing and exploring IRC-assessed ORR as its primary end point. The secondary end points include DOR, PFS, OS, and safety.

The combination regimen was completed by a total of 30 patients and 34 patients were treated with tafasitamab monotherapy following combination therapy.

Tafasitamab is a monoclonal antibody that targets CD19 on tumor cells. Researchers have discovered that CD19 is homogeneously express across B-cell malignancies, including r/r DLBCL, often contributing to the patient population having a poor prognosis. With few treatment options available for these patients, the investigators suggested that a combination of tafasitamab and lenalidomide may present a new treatment opportunity.

“These results, complimented with a favorable safety profile, indicate the utility of this novel immunological combination as a potential treatment option for patients with r/r DLBCL,” said Gilles Salles, MD, PhD, during the poster presentation.