The FDA has granted a priority review designation to a biologics license application for the combination of tafasitamab and lenalidomide for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma.
The FDA has granted a priority review designation to a biologics license application (BLA) for the combination of tafasitamab and lenalidomide (Revlimid) for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).1
The application is based partly on findings from a primary analysis of the L-MIND trial, which showed that tafasitamab in combination with lenalidomide elicited an objective response rate (ORR) of 54%, including a 32% complete response (CR) rate, as assessed by an independent review committee (IRC), in patients with relapsed/refractory DLBCL.2
The BLA is also based on results of RE-MIND, a retrospective observational matched control cohort evaluating real-world efficacy outcomes of relapsed/refractory patients with DLBCL who received lenalidomide monotherapy, and compared them with data from the L-MIND study.3
Under the Prescription Drug User Fee Act, the FDA will make a decision on the BLA by August 30, 2020. Additionally, the FDA informed MorphoSys that it is not planning to hold an Oncologic Drugs Advisory Committee meeting to discuss the application.
"We are extremely pleased that the FDA has accepted filing of our application and granted priority review, as we believe that the combination of tafasitamab and lenalidomide may provide an additional treatment option for patients suffering from DLBCL, who have relapsed after or are refractory to the current standard of care," Malte Peters, MD, chief development officer of MorphoSys, the developer of tafasitamab, stated in a press release. "We would like to thank all patients participating in our clinical studies and we will continue to work relentlessly towards making tafasitamab available to patients."
Tafasitamab is an investigational, humanized Fc-engineered CD19-directed monoclonal antibody. In 2017, the combination of tafasitamab and lenalidomide was granted a breakthrough therapy designation for use in this setting.
In the single-arm, open-label, phase II L-MIND study, investigators evaluated the combination of tafasitamab and lenalidomide in patients with relapsed/refractory DLBCL after ≤2 prior lines of therapy, including an anti-CD20 agent, who are ineligible for high-dose chemotherapy and subsequent autologous stem cell transplant.
The primary endpoint is ORR; secondary endpoints include duration of response (DOR), progression-free survival (PFS), and overall survival (OS). At the data cutoff date of November 30, 2018, the primary analysis included 80 patients enrolled into the trial who had received tafasitamab/lenalidomide and had been followed-up as per protocol for ≥1 year. Efficacy results in this update were based on response rates assessed by an independent review committee for all 80 patients.
Updated results, which were presented at the 2019 ASCO Annual Meeting, also showed that encouraging activity was reported across most patient subgroups, including those who were refractory to prior therapies. The median time to response, and to CR, was 1.8 months and 3.4 months, respectively. The median DOR was not reached; the 12-month DOR rate for patients in CR was 87%.
In the intent-to-treat analysis, the investigator-assessed ORR was 58%, the CR rate was 33%, and the PR rate was 25%. The stable disease rate was 15% and 19% of patients experienced disease progression; 9% of patients were not evaluable. Moreover, the 12-month DOR rate was 70.1% and, specifically in patients who achieved a CR, was 87.0%.
The regimen was also found to be well tolerated and no unexpected toxicities were observed. The most common grade ≥3 treatment-emergent adverse events (AEs) were neutropenia, thrombocytopenia, febrile neutropenia, and anemia. However, neutropenia was well manageable and the majority of patients (81%) recovered within 1 week.
Treatment-related serious AEs included mainly infections (10%) and febrile neutropenia (5%). The treatment discontinuation rate due to AEs were 5%, and 51% of patients required a dose reduction from lenalidomide due to an AE.
In the observational retrospective Re-MIND study, researchers isolated the contribution of tafasitamab in combination with lenalidomide to demonstrate the combinatorial effect. The study compares real-world response data of patients with relapsed/refractory DLBCL who received single-agent lenalidomide with the efficacy outcomes of the tafasitamab/lenalidomide combination from the L-MIND trial. Efficacy data were collected from 490 patients with relapsed/refractory DLBCL in the United States and European Union.
Qualification criteria for matching patients of both studies were prespecified; therefore, 76 eligible Re-MIND patients were identified and matched 1:1 to 76 of 80 L-MIND patients, based on key baseline characteristics. ORRs were validated based on the subset of 76 patients in Re-MIND and L-MIND, respectively.
Results showed that a statistically significant superior best ORR was observed with tafasitamab/lenalidomide combination compared with lenalidomide monotherapy, at 67.1% (95% CI, 55.4-77.5) and 34.2% (95% CI, 23.7-46.0), respectively (P <.0001).
Moreover, key secondary endpoints favored the combination. The CR rate was 39.5% with tafasitamab/lenalidomide combination versus 11.8% with single-agent lenalidomide. The median OS was not reached in the tafasitamab/lenalidomide combination compared with 9.3 months in the lenalidomide-alone arm (HR, 0.47; 95% CI, 0.30-0.73; P <.0008).