Safety and efficacy of tafasitamab with or without lenalidomide added to first-line R-CHOP for DLBCL: the phase 1b First-MIND study

Author(s): David Belada¹; Katerina Kopeckova²; Juan Miguel Bergua Burgues³; Don Stevens⁴; Marc André⁵; Ernesto Perez Persona^6,7; Petra Pichler^8,9; Philipp B. Staber¹⁰; Marek Trneny¹¹; Johannes Duell¹²; Maeve Waldron-Lynch¹³; Steve Wagner¹⁴; Amitava Mukhopadhyay¹⁴; Maren Dirnberger-Hertweck¹⁴; John M. Burke¹⁵; Grzegorz S. Nowakowski¹⁶;

Source: Blood (2023) 142 (16): 1348–1358

Dr. Maen Hussein's Thoughts

Speaking of tafatistamab, it seems it is fairly tolerable in first line with almost 75% CR added to RCHOP, adding lenolidomie 86% CR, but this is a phase 1b. Awaiting phase 3 data, we may have another first line option or may the first line option.

KEY POINTS

The novel combination of tafasitamab ± lenalidomide + R-CHOP showed signs of efficacy in patients with untreated DLBCL, with no new safety signals.
The results, including a post hoc analysis in patients with high-risk disease (IPI 3-5), support the ongoing phase 3 frontMIND trial.

VISUAL ABSTRACT

ABSTRACT

Anti-CD19 immunotherapy tafasitamab is used in combination with lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. Open-label, phase 1b, First-MIND study assessed safety and preliminary efficacy of tafasitamab + R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) ± lenalidomide as first-line therapy in patients with DLBCL. From December 2019 to August 2020, 83 adults with untreated DLBCL (International Prognostic Index 2-5) were screened and 66 were randomly assigned (33 per arm) to R-CHOP-tafasitamab (arm T) or R-CHOP-tafasitamab-lenalidomide (arm T/L) for 6 cycles. Primary end point was safety; secondary end points included end-of-treatment (EoT) overall response rate (ORR) and complete response (CR) rate. All patients had ≥1 treatment-emergent adverse event, mostly grade 1 or 2. Grade ≥3 neutropenia and thrombocytopenia occurred, respectively, in 57.6% and 12.1% (arm T) and 84.8% and 36.4% (arm T/L) of patients. Nonhematologic toxicities occurred at similar rates among arms. R-CHOP mean relative dose intensity was ≥89% in both arms. EoT ORR was 75.8% (CR 72.7%) in arm T and 81.8% (CR 66.7%) in arm T/L; best ORR across visits was 90.0% and 93.9%. Eighteen-month duration of response and of CR rates were 72.7% and 74.5% (arm T) and 78.7% and 86.5% (arm T/L); 24-month progression-free and overall survival rates were 72.7% and 90.3% (arm T) and 76.8% and 93.8% (arm T/L). Manageable safety and promising signals of efficacy were observed in both arms. Potential benefit of adding tafasitamab + lenalidomide to R-CHOP is being investigated in phase 3 frontMIND (NCT04824092). This study is registered at www.clinicaltrials.gov as #NCT04134936.

Author Affiliations

¹4th Department of Internal Medicine—Hematology, Charles University, Hospital and Faculty of Medicine, Hradec Králové, Czech Republic; ²Department of Oncology of the 2nd Faculty of Medicine of Charles University and University Hospital in Motol, Prague, Czech Republic; ³Department of Hematology, Hospital San Pedro de Alcantara, Cáceres, Spain; ⁴Norton Cancer Institute—St. Matthews Campus, Louisville, KY; ⁵Department of Hematology, Université Catholique de Louvain, CHU UCL Namur, Yvoir, Belgium; ⁶Bioaraba (Onco-hematology Research Group), Vitoria-Gasteiz, Spain; ⁷Department of Hematology, Osakidetza Basque Health Service, Araba University Hospital, Vitoria-Gasteiz, Spain; ⁸Department of Internal Medicine, University Hospital of St. Pölten, St. Pölten, Austria; ⁹Karl Landsteiner University of Health Sciences, Karl Landsteiner Institute for Nephrology and Hemato Oncology, St. Pölten, Austria; ¹⁰Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria; ¹¹Charles University General Hospital, Prague, Czech Republic; ¹²Medizinische Klinik und Poliklinik II, Universitätsklinik Würzburg, Würzburg, Germany; ¹³MorphoSys US Inc, Boston, MA; ¹⁴MorphoSys AG, Planegg, Germany; ¹⁵US Oncology Research and Rocky Mountain Cancer Centers, Aurora, CO; ¹⁶Division of Hematology, Mayo Clinic, Rochester, MN

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