Tafasitamab/Lenalidomide Shows Efficacy for 2+ Years in R/R DLBCL

Tafasitamab-cxix (Monjuvi) plus lenalidomide (Revlimid) showed long-term efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who were treated for at least 2 years, according to results presented in a poster session at the Tenth Annual Meeting of the Society of Hematologic Oncology (SOHO 2022).¹

Results from the single-arm, open-label, multicenter phase 2 L-MIND trial (NCT02399085) showed that 23 out of 27 patients were still alive after at least 2 years of treatment, and 6 patients remained on treatment for 5 years or more. Patients also showed fewer adverse events (AEs) after transitioning from combination therapy to tafasitamab monotherapy.

“The new long-term follow-up results from L-MIND at SOHO 2022 highlight the potential of tafasitamab in providing long-term efficacy in patients with relapsed or refractory diffuse large B-cell lymphoma,” Johannes Duell, MD, from University Hospital Wuerzburg Medical Clinic and Polyclinic, said in a press release.² “The fact that 6 of the 27 patients who responded received treatment for 5 or more years—with another 7 patients nearing the 5-year mark—points to the durable response induced by tafasitamab.”

The L-MIND study evaluated the combination of tafasitamab, a humanized, Fc-modified, anti-CD19 monoclonal antibody, in combination with lenalidomide in patients with R/R DLBCL who were ineligible for autologous stem cell transplant. The prior results showed that for the primary end point of best overall response rate (ORR), 55% had a response, including 37% complete responses (CRs).³ The median duration of response (DOR) was 21.7 months. These results led to an accelerated FDA approval in July 2020. Secondary end points included DOR, progression-free survival, overall survival, and safety.

There were 81 patients enrolled in the trial who had received between 1 and 3 prior therapies for DLBCL. They received tafasitamab once weekly for the first 3 28-day cycles, followed by every 2 weeks for cycles 4 to 12, and lenalidomide on days 1 to 21 of cycles 1 to 12. Following 12 cycles, patients received tafasitamab alone every 2 weeks until disease progression.

At the latest data cutoff of February 15, 2022, 27 out of 81 patients (34%) received tafasitamab for at least 2 years.¹ Of the 4 patients who were treated for 2 years but were not confirmed to be alive, one died of an unknown cause, 2 died due to AEs that were deemed unrelated to study treatment, and one was lost to follow-up. Thirteen patients remained on treatment, while 14 patients discontinued treatment after 2 years or more of treatment. Four of those patients who discontinued treatment did so due to disease progression.

A CR was achieved by 23 patients, including the 4 patients who were primary refractory. Two of 4 patients who achieved a partial response remained on treatment. Of the 12 patients who were in follow-up for OS, 6 continued treatment and 6 discontinued treatment. The median DOR, PFS, and OS were not reached.

In terms of safety, the 27 patients who had at least 2 years of treatment had significantly lower incidence of all-grade AEs and grade 3 or higher AEs once lenalidomide had been discontinued, and no new safety signals were reported in the monotherapy period. The majority of AEs were grades 1 or 2.

Looking at the most common all-grade AEs, there were 89 neutropenia events in the first 12 months vs 27 afterward on tafasitamab monotherapy. There were 24 diarrhea events in the first 12 months vs 10 afterward. The exposure-adjusted incidence rate of neutropenia in the first 12 months in terms of events/patient-year was 3.87 for all-grade neutropenia and 1.91 for grade 3 or higher neutropenia, which declined to 0.87 and 0.45, respectively, with tafasitamab monotherapy. The exposure-adjusted rate of diarrhea was 1.04 for all-grade and 0.04 for grade 3 or higher in the first 12 months, which declined to 0.32 and 0, respectively.

“The body of data presented at SOHO shows the long-term duration of response to tafasitamab in some patients with R/R DLBCL not eligible for autologous stem cell transplant,” said Malte Peters, MD, MorphoSys chief research and development officer, in a statement.² “These long-term follow-up results for L-MIND reaffirm our belief that tafasitamab plus lenalidomide remains the in-practice, outpatient targeted immunotherapy of choice for this group of patients.”

_References:

_{1. Duell J, Jurczak W, Liberati AM, et al. L-MIND: A safety and efficacy analysis of tafasitamab in patients with relapsed/refractory diffuse large B-cell lymphoma receiving treatment for at least 2 years. Poster presented at: 10th Annual Meeting of the Society of Hematologic Oncology (SOHO 2022); September 28-October 1, 2022; Houston TX. Poster ABCL-388}

_{2. MorphoSys presents new long-term data from L-MIND suggesting durable response to treatment with Monjuvi® (tafasitamab-cxix) for patients with R/R DLBCL. MorphoSys. September 28, 2022. Accessed October 4, 2022. https://bit.ly/3ruAsOL}

_{3. FDA grants accelerated approval to tafasitamab-cxix for diffuse large B-cell lymphoma. FDA. Updated August 3, 2020. Accessed October 4, 2022. https://bit.ly/3CvJYHC}