FDA Approves Tafasitamab Plus Lenalidomide in Relapsed/Refractory DLBCL

August 1, 2020

The FDA has approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant.

The FDA has approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide (Revlimid) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant.1

The humanized Fc-modified cytolytic CD19-targeting monoclonal antibody was granted accelerated approval based on overall response rate (ORR) data; notably, this marks the first approval of a second-line therapy for adult patients who had progressed during or after first-line treatment. Continued approval of the agent will be dependent on verification in confirmatory trials.

“We are incredibly proud that the FDA has approved [tafasitamab] in combination with lenalidomide as the first treatment in second line for patients with relapsed or refractory DLBCL,” Jean-Paul Kress, MD, chief executive officer of MorphoSys, stated in a press release. “This approval marks an important step in MorphoSys’ transformation into a fully integrated biopharmaceutical company. We remain committed to developing innovative to developing innovative treatments to improve the lives of patients with serious diseases.”

The regulatory decision was based on data from the phase 2 L-MIND trial, which demonstrated that tafasitamab in combination the lenalidomide elicited an ORR of 55%, which was comprised of a complete response (CR) rate of 37% and a partial response (PR) rate of 18%. The median duration of response (DOR) was 21.7 months.2

In the open-label, multicenter, single-arm trial, investigators examined the combination in patients with relapsed/refractory DLBCL following ≤2 previous lines of therapy, including an anti-CD20 agent, who were not considered to be candidates for high-dose chemotherapy and subsequent autologous stem cell transplant.

The primary end point of the trial is ORR, while secondary end points include DOR, progression-free survival (PFS), and overall survival (OS). At the November 30, 2018 cutoff date, 80 patients were enrolled on the trial and had received the combination; they had been followed up as per study protocol for ≥1 year.

A previous update presented during the 2019 ASCO Annual Meeting demonstrated that the tafasitamab/lenalidomide combination demonstrated promising activity across most patient subgroups analyzed, including those who were refractory to previous treatments. The median time to response was 1.8 months and the median time to a CR was 3.4 months. The median DOR had not yet been reached, but the 12-month DOR rate for those who had achieved a CR was 87%.

Moreover, the investigator-assessed ORR was 58% in the intent-to-treat analysis, with a CR rate of 33% and a PR rate of 25%. Fifteen percent of patients achieved stable disease, while 19% had progressive disease. Nine percent of patients were determined to be unevaluable. The 12-month DOR in this population was 70.1%; it was even higher in those who achieved a CR, at 87.0%.

With regard to safety, the Warnings and Precautions for tafasitamab include infusion-related reactions (6%), serious or severe myelosuppression, including neutropenia (50%), thrombocytopenia (18%), anemia (7%), infections (73%), and embryo-fetal toxicity. Approximately 4% of patients (3.7%) discontinued treatment because of neutropenia.

Moreover, the most commonly reported adverse reactions (≥20%) included neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and a decrease in appetite.

In the retrospective Re-MIND study, investigators isolated the contribution of tafasitamab in combination with lenalidomide to show the combinatorial effect.3 To do this, real-world response data of patients with relapsed/refractory DLBCL who had received lenalidomide monotherapy were analyzed, along with the outcomes of the combination from the L-MIND trial. Efficacy data were gathered from a total of 490 patients with relapsed/refractory disease in the United States and the European Union.

Qualification criteria for matching patients of both studies were prespecified. Seventy-six eligible patients from Re-MIND were identified and matched 1:1 to 76 patients from L-MIND, based on specific baseline characteristics. ORRs were validated based on the 76-patient subsets from both trials.

Results from the analysis demonstrated a statistically significant superior best ORR with the combination compared with lenalidomide alone, at 67.1% versus 34.2%, respectively (P <.0001). Key secondary end points were also found to favor tafasitamab/lenalidomide. The CR rates were 39.5% and 11.8% with the combination and the monotherapy, respectively. The median OS had not yet been reached in the combination arm versus 9.3 months in the single-agent arm (HR, 0.47; 95% CI, 0.30-0.73; P <.0008).

“The FDA approval of Monjuvi brings a new treatment option to patients in dire need across the United States,” Professor Gilles Salles, MD, lead L-MIND investigator and chair of the Clinical Hematology Department at the University of Lyon, stated in the press release. “Today’s FDA decision offers new hope for patients with this aggressive form of DLBCL who progressed during or after first-line therapy.”

Previously, the combination of tafasitamab and lenalidomide received fast track and breakthrough therapy status from the FDA for use in patients with relapsed or refractory DLBCL. The biologics license application for tafasitamab was granted priority review and approved under the FDA's Accelerated Approval program.

The combination is anticipated to become commercially available in the United States in the near future, according to MorphoSys, who will co-commercialize the combination with Incyte in the United States. Incyte has exclusive commercialization rights outside of the United States.

References

  1. FDA approves Monjuvi (tafasitamab-cxix) in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). News release. MorphoSys AG. July 31, 2020. Accessed July 31, 2020. https://bwnews.pr/3jZhE5g.
  2. Update of the single-arm phase II L-MIND study of MOR208 + lenalidomide (LEN) in relapsed/refractory diffuse large B-cell lymphoma (R-R DLBCL): Response rates in patient subgroups with poor prognosis. J Clin Oncol. 2019;37(suppl 15):7521. doi:10.1200/JCO.2019.37.15_suppl.7521
  3. MorphoSys AG: primary endpoint met in real-world data study demonstrating clinical superiority of the combination of tafasitamab and lenalidomide compared to lenalidomide alone. News release. Morpho Sys AG. October 29, 2019. Accessed July 31, 2020. https://bit.ly/2VAHjr0.

x