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

June 15, 2020
Nichole Tucker

Nichole Tucker, MA, is the Web Editor for Targeted Oncology. Tucker received her Bachelor of Arts in Mass Communications from Virginia State University and her Master of Arts in Media & International Conflict from University College Dublin.

“These results, complimented with a favorable safety profile, indicate the utility of this novel immunological combination as a potential treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma."

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.