Updated Data Confirm Long-Term Benefit With Tafasitamab/Lenalidomide in Relapsed/Refractory DLBCL

Gilles Salles, MD, PhD

Tafasitamab (MOR208) plus lenalidomide (Revlimid) followed by tafasitamab monotherapy was confirmed to induce durable responses and a clinically meaningful overall survival (OS) benefit in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to updated data from the phase 2 L-MIND study (NCT02399085).

Results from the trial presented during the 2020 European Hematology Association Annual Congress showed that after 2 or more years of follow-up, the objective response rate (ORR) with tafasitamab plus lenalidomide was 58.8%, as assessed by an independent review committee (IRC), proving to be consistent to what had been observed in the primary analysis. Of these patients, 41.3% experienced a complete response (CR) and 17.5% had a partial response (PR). Moreover, 15.0% of patients achieved stable disease, while 16.3% experienced disease progression, and 10.0% of patients were determined to be unevaluable.¹

Of those who responded to the treatment, the IRC-assessed median duration of response (DOR) was 34.6 months (95% CI, 26.1-34.6). Specifically, the median DOR in those who achieved a CR was not reached (NR; 95% CI, 26.1-NR) and 5.6 months in those with a PR (95% CI, 2.2-34.6). The IRC-assessed median OS with the regimen was 31.6 months (95% CI, 18.3-NR) at a median follow-up of 31.8 months, and the median progression-free survival (PFS) was 16.2 months (95% CI, 6.3-NR) at a median follow-up of 22.6 months.

“The data from this long-term analysis of the L-MIND study are consistent with findings from the primary analysis that were recently published,” said lead author Gilles Salles, MD, PhD, head of the Hematology Department of the South Lyon University Hospital, in a virtual poster presentation during the meeting. “After more than 2 years of follow-up, we see that responses continue to be durable and the favorable PFS and OS results indicate a clinically meaningful survival benefit for these transplant-ineligible patients who currently have few treatment options available.”²

In the open-label, single-arm, phase 2 study, investigators set out to characterize the safety and efficacy of tafasitamab in combination with lenalidomide in adult patients with DLBCL who have received at least 1, but no more than 3, prior systemic regimens and who were ineligible for high-dose chemotherapy with autologous stem cell transplant. The primary end point of the trial was ORR, which was assessed by an IRC. Secondary end points included disease control rate, DOR, PFS, percentage of patients with OS, and safety.

To be eligible for enrollment, patients had to be aged 18 years or older with relapsed/refractory DLBCL and have received 1-3 prior systemic therapies, including at least 1 CD20-targeting regimen. Additionally, patients had to have an ECOG performance status of 0 to 2. Participants received intravenous tafasitamab at 12 mg/kg once weekly during cycles 1 to 3, with a loading dose on day 4 of cycle 1 followed by dosing every 2 weeks during cycles 4 to 12; the agent was given in 28-day treatment cycles. Lenalidomide was orally administered at a dose of 25 mg on days 1 through 21 of cycles 1 to 12. After cycle 12, patients who did not progress received tafasitamab every 2 weeks until progression. A total of 80 patients received treatment with tafasitamab and lenalidomide. After ≥2 years of follow-up, a total of 22 patients were still receiving tafasitamab monotherapy; 59 patients had discontinued treatment.

Regarding safety, the doublet regimen was found to be well tolerated. The most common grade 3 or higher hematologic treatment-emergent adverse effects (TEAEs) included neutropenia (49.4%), thrombocytopenia (17.3%), and febrile neutropenia (12.3%). The most common grade ≥3 non-hematological TEAEs were pneumonia (8.6%) and hypokalemia (6.2%). Serious AEs reported by ≥2 patients included pneumonia (8.6%), febrile neutropenia (6.2%), pulmonary embolism (3.7%), and respiratory AEs like bronchitis, lower respiratory tract infection, atrial fibrillation, and congestive cardiac failure (2.5% each).

Results from the primary analysis of the trial showed an investigator-assessed ORR of 58% with the doublet in this patient population.2 At a median follow-up of 12 months, the median investigator-assessed DOR was not reached (95% CI, NR- NR), the median PFS was 16.2 months (95% CI, 6.3-NR), and the median OS was NR (95% CI, 18.6-NR).

Based in part on these findings, in March 2020, the FDA granted a priority review designation to a biologics license application for tafasitamab and lenalidomide for the treatment of patients with relapsed/refractory DLBCL. These findings also supported the European Medicines Agency’s decision to validate a marketing authorization in May 2020 for the combination, followed by single-agent lenalidomide, for the treatment of adult patients with relapsed/refractory DLBCL, including DLBCL arising from low-grade lymphoma, who are transplant ineligible.

References

1. Salles G, Duell J, Gonzalez-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: 2020 European Hematology Association Congress; June 11-21, 2020; Virtual. Abstract EP1201.
2. Salles G, Duell J, González Barca E, et al. Primary analysis results of the single-arm phase II study of MOR208 plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (L-MIND). Hematol Oncol. 2019;37(S2). doi:10.1002/hon.130_2629