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Clinical Trial
. 2023 Oct 19;142(16):1348-1358.
doi: 10.1182/blood.2023020637.

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

David Belada  1 , Katerina Kopeckova  2 , Juan Miguel Bergua Burgues  3 , Don Stevens  4 , Marc André  5 , Ernesto Perez Persona  6   7 , Petra Pichler  8   9 , Philipp B Staber  10 , Marek Trneny  11 , Johannes Duell  12 , Maeve Waldron-Lynch  13 , Steve Wagner  14 , Amitava Mukhopadhyay  14 , Maren Dirnberger-Hertweck  14 , John M Burke  15 , Grzegorz S Nowakowski  16
Affiliations
Clinical Trial

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

David Belada et al. Blood. .

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.

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Conflict of interest statement

Conflict-of-interest disclosure: D.B. received consultancy fees from Roche, Gilead Sciences, Janssen-Cilag, Takeda, MorphoSys AG, and Debiopharm Group; travel, accommodations, and expenses from Roche, Gilead Sciences, and Takeda; and research funding from Roche, Gilead Sciences, Janssen-Cilag, Takeda, MorphoSys AG, Pharmacyclics, Archigen Biotech, and Dr Reddy’s Laboratories. M.A. received consultancy from Incyte, Gilead, Karyopharm, Bristol Myers Squibb, and Takeda; travel, accommodations, and expenses from Roche, Gilead, Bristol Myers Squibb, Celgene, and AbbVie; and research funding from Johnson & Johnson, Roche, and Takeda. E.P.P. received consultancy fees from Amgen, Bristol Myers Squibb/Celgene, Sanofi, GlaxoSmithKline, and Incyte; travel, accommodations, and expenses from Amgen, Bristol Myers Squibb/Celgene, and AbbVie; and speaker's bureau fees from Amgen, Bristol Myers Squibb/Celgene, AbbVie, Takeda, Sanofi, and AstraZeneca. P.B.S. received consultancy fees from Roche, AbbVie, Gilead, Janssen, AstraZeneca, Takeda, MSD, Bristol Myers Squibb, Incyte, and BeiGene; research funding from Roche, Takeda, and Incyte; and honoraria from Roche, AbbVie, Gilead, Janssen, AstraZeneca, MSD, Bristol Myers Squibb, Incyte, and BeiGene. M.T. received consultancy fees from AbbVie, Amgen, Bristol Myers Squibb, Gilead, Incyte, Janssen, MorphoSys AG, Roche, Takeda, Celgene, and Novartis and travel, accommodations, and expenses from AbbVie, Bristol Myers Squibb, Gilead, Janssen, Roche, and Takeda; received honoraria from AbbVie, Amgen, Bristol Myers Squibb, Incyte, Janssen, MorphoSys AG, Roche, Takeda, Novartis, Portola, and AstraZeneca; is a member in an entity’s board of directors or advisory committees from AbbVie, Bristol Myers Squibb, Incyte, Janssen, MorphoSys AG, Roche, Takeda, Novartis, and Portola; and is employed by the 1st Faculty of Medicine, Charles University, General Hospital in Prague. J.D. received research funding from MorphoSys AG and Regeneron. M.W.-L. is employed at MorphoSys AG. S.W. is employed at MorphoSys AG. A.M. is employed at MorphoSys AG. M.D.-H. was employed at MorphoSys AG (until 31 December 2021). J.M.B. received consultancy fees from MorphoSys AG, Adaptive Biotechnologies, Verastem Oncology, AstraZeneca, Bristol Myers Squibb, Kymera Therapeutics, X4 Pharmaceuticals, AbbVie, SeaGen, Kura Oncology, Roche/Genentech, Epizyme, and BeiGene and received speaker's bureau fees from SeaGen and BeiGene. G.S.N. received consultancy fees from Celgene, MorphoSys AG, Genentech, Selvita, Debiopharm Group, and Kite/Gilead; received research funding from Celgene, NanoString Technologies, and MorphoSys AG; and is a member on an entity’s board of directors or advisory committees at Celgene, MorphoSys AG, Genentech, Selvita, Debiopharm Group, and Kite/Gilead. The remaining authors declare no competing financial interests.

The current affiliation for M.D.-H is Daiichi-Sankyo Europe GmbH, Munich, Germany.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Study design. ∗In the lenalidomide arm, venous thromboembolism prophylaxis with either low-molecular weight heparins or aspirin is mandatory (according to institutional guidelines). †Rituximab (375 mg/m2) and CHOP chemotherapy included cyclophosphamide (750 mg/m2 IV), doxorubicin (50 mg/m2 IV), and vincristine (1.4 mg/m2 [maximum dose = 2 mg] IV) on day 1 of every 21-day cycle and prednisone/prednisolone (100 mg/day PO) on days 1 to 5. The day 1 steroid dose being part of CHOP (100 mg prednisone/prednisolone, or equivalent, PO or IV) could be used as a further component of premedication before tafasitamab infusion. L, lenalidomide; NOS, not otherwise specified; PO, orally; R, randomized; T, tafasitamab.
Figure 2.
Figure 2.
Patient disposition. Notably, also some patients with PD at EoT have entered the FU period. ∗All the patients randomized were included in efficacy analysis (FAS) and safety analysis. †Discontinuations of other study components not shown. ‡Completed study: all FU visits completed. §PD and participation in another clinical trial. AE, adverse event; COVID-19, coronavirus disease 2019; FU, follow-up; PD, progressive disease.
Figure 3.
Figure 3.
Most frequent hematologic and nonhematologic TEAEs occurring in ≥10% of patients in either study arm.
Figure 4.
Figure 4.
Probability of PFS in arm T and arm T/L at 24 months.
Figure 5.
Figure 5.
Probability of OS in arm T and arm T/L at 24 months.
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References

    1. 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
    1. 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. - PMC - PubMed
    1. 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
    1. 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.
    1. 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. - PMC - PubMed

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