MorphoSys AG announced final safety and efficacy results from firstMIND, a Phase 1b, open-label, randomized safety study combining tafasitamab or tafasitamab plus lenalidomide with standard R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Additional analyses highlighted the prognostic potential of sensitive circulating tumor (ct) DNA minimal residual disease (MRD) assays in patients with DLBCL after first-line therapy. These results are being presented during oral and poster sessions on December 10, 2022, at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition in New Orleans, Louisiana.

Tafasitamab, marketed in the U.S. as Monjuvi® and outside the U.S. by Incyte as Minjuvi®, is a CD19 targeting immunotherapy. Tafasitamab received an accelerated approval and conditional approval by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively, for patients with certain types of DLBCL that has come back (relapsed) or that did not respond to previous treatment (refractory) and who are not eligible to receive a stem cell transplant. The final analysis of firstMIND demonstrated an overall response rate at the end of treatment of 75.8% for patients treated with tafasitamab plus R-CHOP (n=33) and 81.8% for patients treated with tafasitamab, lenalidomide and R-CHOP (n=33).

In the tafasitamab, lenalidomide and R-CHOP arm, 24-month progression-free survival (PFS) and overall survival (OS) rates were 76.8% and 93.8%, respectively. PFS and OS rates were 73.6% and 95.2%, respectively, for patients with high-intermediate to high-risk DLBCL (International Prognostic Index [IPI] 3-5) treated with tafasitamab, lenalidomide and R-CHOP (n=22). Improved PFS was observed in MRD-negative patients compared with MRD-positive patients.

The most common hematological treatment emergent adverse events in both patients treated with tafasitamab plus R-CHOP and patients treated with tafasitamab, lenalidomide and R-CHOP were neutropenia (60.6% and 84.8%, respectively), anemia (51.5% and 60.6%), thrombocytopenia (21.2% and 42.4%) and leukopenia (30.3% and 27.3%), respectively. Rates of febrile neutropenia were equal (18.2%) in both arms. Non-hematological adverse events were well balanced between arms and were mostly grades 1 and 2. No unexpected toxicities or new safety signals were identified in the final analysis. A second poster presentation and an oral presentation both demonstrate the potential of sensitive ctDNA MRD assays to predict PFS outcomes following first-line treatment in patients with DLBCL.

In the poster presentation, negative MRD as detected by next generation sequencing detection of ctDNA after treatment with tafasitamab in combination with lenalidomide and R-CHOP in the firstMIND study was associated with a significant improvement in PFS (p=0.008). One of 12 patients who were MRD-negative after treatment had developed disease progression by the time of data cutoff, when all patients had completed 18 months of post-treatment follow-up. The oral presentation highlighted the prognostic utility of sensitive ctDNA MRD assays in a meta-analysis of five prospective studies of first-line treatment regimens for large B-cell lymphomas.

Achievement of MRD negativity after any of the first three cycles of treatment was strongly prognostic for PFS (p=0.0003), and failure to achieve MRD negativity by the end of treatment was associated with the highest risk for progression. Detection of ctDNA MRD at levels below 1 in 10,000 (0.01%) was essential to achieve 99% sensitivity.