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.

4th Department of Internal Medicine Hematology Charles University Hospital and Faculty of Medicine Hradec Králové Czech Republic

Bioaraba Vitoria Gasteiz Spain

Charles University General Hospital Prague Czech Republic

Department of Hematology Hospital San Pedro de Alcantara Cáceres Spain

Department of Hematology Osakidetza Basque Health Service Araba University Hospital Vitoria Gasteiz Spain

Department of Hematology Université Catholique de Louvain CHU UCL Namur Yvoir Belgium

Department of Internal Medicine University Hospital of St Pölten St Pölten Austria

Department of Oncology of the 2nd Faculty of Medicine of Charles University and University Hospital in Motol Prague Czech Republic

Division of Hematology and Hemostaseology Department of Medicine 1 Medical University of Vienna Vienna Austria

Division of Hematology Mayo Clinic Rochester MN

Karl Landsteiner University of Health Sciences Karl Landsteiner Institute for Nephrology and Hemato Oncology St Pölten Austria

Medizinische Klinik und Poliklinik 2 Universitätsklinik Würzburg Würzburg Germany

MorphoSys AG Planegg Germany

MorphoSys US Inc Boston MA

Norton Cancer Institute St Matthews Campus Louisville KY

US Oncology Research and Rocky Mountain Cancer Centers Aurora CO

Blood. 2023 Oct 19;142(16):1331-1332. doi: 10.1182/blood.2023021521. PubMed

Zobrazit více v PubMed

Wild CP, Weiderpass E, Stewart BW, editors. World Cancer Report: Cancer Research for Cancer Prevention. International Agency for Research on Cancer; 2020. http://publications.iarc.fr/586

Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116(12):2040–2045. PubMed PMC

Sehn LH, Berry B, Chhanabhai M, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007;109(5):1857–1861. PubMed

Gleeson M, Counsell N, Cunningham D, et al. A comparison of prognostic indices in diffuse large B-cell lymphoma within the UK NCRI R-CHOP 14 versus 21 phase III trial [abstract] Blood. 2018;132(suppl 1):2956.

Younes A, Sehn LH, Johnson P, et al. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non–germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019;37(15):1285–1295. PubMed PMC

Nowakowski GS, Chiappella A, Gascoyne RD, et al. ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021;39(12):1317–1328. PubMed PMC

Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med. 2022;386(4):351–363. PubMed

Davies A, Cummin TE, Barrans S, et al. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20(5):649–662. PubMed PMC

Zinzani PL, Rigacci L, Cox MC, et al. Lenalidomide monotherapy in heavily pretreated patients with non-Hodgkin lymphoma: an Italian observational multicenter retrospective study in daily clinical practice. Leuk Lymphoma. 2015;56(6):1671–1676. PubMed

Thieblemont C, Tilly H, Gomes da Silva M, et al. Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and Prednisone. J Clin Oncol. 2017;35(22):2473–2481. PubMed

Nowakowski GS, Hong F, Scott DW, et al. Addition of lenalidomide to R-CHOP improves outcomes in newly diagnosed diffuse large B-cell lymphoma in a randomized phase II US Intergroup Study ECOG-ACRIN E1412. J Clin Oncol. 2021;39(12):1329–1338. PubMed PMC

Lenz G, Wright G, Dave SS, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008;359(22):2313–2323. PubMed PMC

Horton HM, Bernett MJ, Pong E, et al. Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia. Cancer Res. 2008;68(19):8049–8057. PubMed

Duell J, Abrisqueta P, Andre M, et al. Abstract CT022 - five-year efficacy and safety of tafasitamab in patients with relapsed or refractory DLBCL: final results from the phase II L-MIND study. Cancer Res. 2023;83(suppl 8):CT022.

Monjuvi (tafasitamab-cxix). MorphoSys. Prescribing information. https://www.monjuvi.com/pi/monjuvi-pi.pdf 2021.

Minjuvi. European Medicines Agency. Summary of product characteristics (SmPC) https://www.ema.europa.eu/en/documents/product-information/minjuvi-epar-product-information_en.pdf 2022.

Phase Ib study to assess safety and preliminary efficacy of tafasitamab or tafasitamab plus lenalidomide in addition to R-CHOP in patients with newly diagnosed DLBCL. ClinicalTrials.gov identifier: NCT04134936. Updated 15 March 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04134936

Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–3068. PubMed PMC

Tafasitamab + lenalidomide + R-CHOP versus R-CHOP in newly diagnosed high-intermediate and high risk DLBCL patients. ClinicalTrials.gov identifier: NCT04824092. Updated 6 April 2023. https://classic.clinicaltrials.gov/ct/show/NCT04824092

Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21(7):978–988. PubMed

McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16(8):2825–2833. PubMed

Zobrazit více v PubMed

ClinicalTrials.gov
NCT04824092, NCT04134936