On December 10, 2022 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported 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) (Press release, MorphoSys, DEC 10, 2022, View Source [SID1234625066]). 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) (Free ASH Whitepaper) Annual Meeting and Exposition in New Orleans, Louisiana.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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 from firstMIND underscores the therapeutic potential of tafasitamab in combination with lenalidomide added on to standard R-CHOP therapy for patients with newly diagnosed DLBCL," said Greg S. Nowakowski, M.D., Professor of Medicine and Oncology at the Mayo Clinic and lead investigator for the firstMIND trial. "This regimen, which is also being investigated in the Phase 3 frontMIND trial, represents an ongoing effort to address a critical need in patients with high-risk DLBCL, many of whom relapse after current first-line therapy. I am encouraged by the results from firstMIND and eagerly anticipate the Phase 3 data on the combined efficacy of tafasitamab, lenalidomide and R-CHOP in newly diagnosed patients with DLBCL."
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.
"These new data suggest that assays that can better detect minimal residual disease carry important prognostic value and may serve as surrogate markers for clinical benefit in future lymphoma trials," said Dr. Tim Demuth, Chief Research and Development Officer at MorphoSys. "These insights, along with the final results from firstMIND and growing body of data supporting Monjuvi in second-line therapy, give us greater understanding of how to improve outcomes at diagnosis or first relapse. We are eager to learn through frontMIND about the potential of tafasitamab plus lenalidomide to augment a standard of care in first-line therapy for patients newly diagnosed with high-intermediate and high-risk DLBCL."