FDA Approves Tafasitamab/Lenalidomide for R/R DLBCL

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

The combination was approved through the FDA’s accelerated approval program and continued approval may be contingent upon verification of clinical benefit from confirmatory clinical trials. 

“There is a large proportion of patients who can benefit from this option and I see it as one of the major options in the relapsed/refractory setting for patients who are not transplant eligible or have failed this path and I think this is important,” Gilles Salles, MD, PhD, professor at the University of Lyon and chair of the Department of Hematology at the University Hospital in Lyon, France, who will soon be joining Memorial Sloan Kettering Cancer Center in New York, told Targeted Oncology. “I think it’s great news for patients with lymphoma and we hope we can offer this form of therapy to them soon and I think this is real progress in the field.”

The combination was granted a priority review based on findings from the phase 2 L-MIND trial, which evaluated the safety and efficacy of the regimen in patients with relapsed/refractory DLBCL, as well as from the observational retrospective cohort RE-MIND study, which looked at real-world use of tafasitamab. Updated results of both studies were presented at the virtual 25th Congress of the European Hematology Association (EHA).2,3

Tafasitamab is a humanized Fc-engineered CD19-directed monoclonal antibody that potentiates antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis.

The single-arm, open-label, multicenter L-MIND study explored the use of tafasitamab and lenalidomide in 81 patients with relapsed/refractory DLBCL who have received 2 prior lines of therapy, including an CD20-directed therapy such as rituximab (Rituxan), and who are not eligible for high-dose chemotherapy and autologous stem cell transplantation. 

Patients received 12 mg/kg intravenous tafasitamab in 4-week cycles, which included administration on day 1 of cycles 1 through 3 with a loading dose on day 4 of cycle 1 and subsequently every 2 weeks for the following cycles. Oral lenalidomide was given at 25 mg on days 1 through 21 for 12 cycles. After the last cycle of the combination regimen, patients were given tafasitamab monotherapy every 2 weeks until disease progression occurred. 

Two-year follow-up results were presented at EHA, showing an objective response rate (ORR) of 58.5% by independent review committee assessment, which consisted of complete responses (CRs) in 41.3% and partial responses (PRs) in 17.5%. An additional 15.0% of patients achieved stable disease. The median duration of response (DOR) was 34.6 months (95% CI, 26.1-34.6).

The median progression-free survival (PFS) was 16.2 months (95% CI, 6.3 to not reached [NR]) and the median overall survival (OS) was 31.6 months (95% CI, 18.3-NR). 

In terms of safety, the most common grade ≥3 hematologic treatment-emergent adverse events (TEAEs) were neutropenia in 49.4%, thrombocytopenia in 17.3%, and febrile neutropenia in 13.2%. Non-hematologic grade ≥3 TEAEs included pneumonia in 8.6% of patients and hypokalemia in 6.2%. 

Serious AEs reported included pneumonia in 8.6%, febrile neutropenia in 6.2%, and pulmonary embolism in 3.7%, as well as bronchitis, lower respiratory tract infection, atrial fibrillation, and congestive cardiac failure in 2.5% each.

The RE-MIND study compared real-world response data from patients receiving lenalidomide monotherapy with findings from patients who received the investigational combination of tafasitamab and lenalidomide. The purpose was to isolate the contribution of tafasitamab specifically to the combination regimen. 

Investigators used a control cohort of 76 patients from the L-MIND study who were compared with health record data collected retrospectively for 450 patients receiving lenalidomide monotherapy that was narrowed down to a group of 76.3 

In the group of patients who received the combination the best ORR was 67.1% with CRs in 39.5% and PRs in 27.4%. Comparatively the best ORR among patients who received lenalidomide monotherapy was 34.2% with CRs in 13.2% and PRs in 21.1%. The ORR odds ratio was 3.9 (95% CI, 1.9-8.1; P <.0001). 

The median PFS was 12.1 months with the combination regimen versus 4.0 months with single-agent lenalidomide (HR, 0.463; 95% CI, 0.307-0.698; P = .0002). The median OS was not reached with the combination treatment versus 9.4 months with lenalidomide monotherapy (HR, 0.499; 95% CI, 0.317-0.785; P = .0026. 

The combination previously received a breakthrough therapy designation from the FDA in 2017 for the treatment of patients with relapsed/refractory DLBCL as well as a prior fast track designation.

“The FDA approval of Monjuvi in combination with lenalidomide helps address an urgent unmet medical need for patients with relapsed or refractory DLBCL in the United States,” said Hervé Hoppenot, CEO of Incyte, in a statement. “At Incyte we are committed to advancing patient care and are proud to bring this new and much-needed targeted therapeutic option to appropriate patients and the clinical community.”


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 and Incyte. July 31, 2020. Accessed July 31, 2020. https://bit.ly/3fgyqZZ

2. Salles G, Duell J, González-Barca E, et al. Long-term outcomes from the phase II L-MIND study of Tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Presented at: Presented at: EHA25 Virtual; June 11-21, 2020. Abstract EP1201.

3. Zinzani PL, Rodgers T, Marino D, et al. RE-MIND study: Comparison of tafasitamab + lenalidomide (L-MIND) vs lenalidomide monotherapy (real-world data) in transplant-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma. Presented at: EHA25 Virtual; June 11-21, 2020. Abstract S238.