The European Medicines Agency has validated a Marketing Authorization for the combination of tafasitamab and lenalidomide, followed by single-agent lenalidomide, for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma, including DLBCL arising from low-grade lymphoma, who are ineligible for autologous stem cell transplant.
Peter Langmuir, MD
The European Medicines Agency (EMA) has validated a Marketing Authorization (MAA) for the combination of tafasitamab and lenalidomide (Revlimid), followed by single-agent lenalidomide, for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from low-grade lymphoma, who are ineligible for autologous stem cell transplant.1
The application is based on findings from the L-MIND study, which is evaluating tafasitamab in combination with lenalidomide as a treatment for patients with relapsed/refractory DLBCL. In the trial, the combination led to a 54% objective response rate (ORR) of 54%, including a 32% complete response (CR) rate, as assessed by an independent review committee (IRC), in this patient population.2
The MAA is also supported by the Re-MIND study, which is an observational, matched control cohort, retrospective study evaluating real-world efficacy outcomes of relapsed/refractory patients with DLBCL who received lenalidomide monotherapy,3 and compared them with data from the L-MIND study.
By validating the MAA, the submission is now complete to begin the formal review process for approval in the European Union.
“The EMA’s validation of the MAA for tafasitamab is a critical step on the path to making tafasitamab available for use in combination with lenalidomide in eligible patients with [relapsed/refractory] DLBCL in Europe,” Peter Langmuir, MD, group vice president, Targeted Therapeutics, Incyte, which develops tafasitamab with MorphoSys, stated in a press release. “We will continue to work closely with the EMA to progress the review of this application, with the hope of bringing this novel therapy to eligible patients as soon as possible.”
If approved, Incyte will hold the marketing authorization for the application; it will also have exclusive commercialization rights for tafasitamab outside of the United States, including Europe.
In March 2020, the FDA 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 DLBCL, also based on the L-MIND and Re-MIND findings. Under the Prescription Drug User Fee Act, the FDA will make a decision on the application by August 30, 2020.
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%.
Regarding safety, 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).