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

Mosunetuzumab Plus Polatuzumab Vedotin in Transplant-Ineligible Refractory/Relapsed Large B-Cell Lymphoma: Primary Results of the Phase III SUNMO Trial

Median progression-free survival (PFS) was significantly longer with mosunetuzumab plus polatuzumab vedotin (Mosun-Pola) than with R-GemOx (11.5 months vs 3.8 months). The overall response rate (ORR) was significantly higher with Mosun-Pola compared with R-GemOx (70% vs 40%; P < .0001), with complete response rates of 51% and 24%, respectively. Cytokine release syndrome (CRS) occurred in fewer than 5% of patients.

Five-Year Outcomes of the POLARIX Study Comparing Pola-R-CHP and R-CHOP in Patients With Diffuse Large B-Cell Lymphoma

Another update demonstrated the superiority of polatuzumab vedotin plus R-CHOP (Pola-R-CHOP) over R-CHOP alone, with improved progression-free survival (PFS) (64% vs 59%). Overall survival (OS) was not statistically significant; however, the hazard ratio was 0.85, with greater benefit observed in high-risk patients.

Remission Assessment by Circulating Tumor DNA in Large B-Cell Lymphoma

Minimal residual disease (MRD) testing after two cycles of therapy and at the end of treatment predicted 2-year progression-free survival (PFS) (96% in MRD-negative patients vs 67% in MRD-positive patients). MRD status was more predictive of treatment outcomes than radiographic imaging in this patient population.

Fixed-duration epcoritamab plus R2 drives favorable outcomes in relapsed or refractory follicular lymphoma

The EPCORE NHL-2 phase 1b/2 trial evaluated fixed-duration epcoritamab plus R2 in R/R FL after at least one prior line, showing impressive efficacy with an overall response rate (ORR) of 96% and a complete response (CR) of 88%, and 2-year rates for remaining in CR (82%), progression-free survival (PFS) (76%), overall survival (OS) (90%), and freedom from next therapy (84%)—all with non-reached medians. High-risk groups did just as well, with CR rates of 90% in primary refractory, 82% in double refractory. MRD negativity was achieved by 86% overall. Safety was manageable, with mostly low-grade CRS (grade 1/2/3: 38%/11%/2%), neutropenia (65%), and COVID-19 (59%)—notably, no CRS-related discontinuations. This chemo-free, off-the-shelf regimen is delivering deep, durable remissions with practical outpatient dosing—something we’ve all been hoping to see for R/R FL.

A phase 2 trial of CHOP with anti-CCR4 antibody mogamulizumab for older patients with adult T-cell leukemia/lymphoma Available to Purchase

The phase 2 trial of Moga-CHOP (CHOP + mogamulizumab) in older patients with aggressive adult T-cell leukemia/lymphoma (ATL) demonstrated a significant improvement in 1-year PFS (36.2% vs 16% historical control), with a 1-year OS of 66.0% and a CR rate of 64.6%. The overall response rate (ORR) was high at 91.7%, and the median overall survival (OS) reached 1.6 years. Notably, CCR4 mutations and Moga-associated cutaneous AEs correlated with better OS, and the regimen was generally tolerable with no unexpected toxicities. Bottom line: Moga-CHOP is now a strong first-line option for older, transplant-ineligible ATL patients, and it’s encouraging to see these survival gains in a population with historically poor outcomes.