Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial

Autor: Meletios A Dimopoulos, Evangelos Terpos, Mario Boccadoro, Sosana Delimpasi, Meral Beksac, Eirini Katodritou, Philippe Moreau, Luca Baldini, Argiris Symeonidis, Jelena Bila, Albert Oriol, Maria-Victoria Mateos, Hermann Einsele, Ioannis Orfanidis, Tahamtan Ahmadi, Jon Ukropec, Tobias Kampfenkel, Jordan M Schecter, Yanping Qiu, Himal Amin, Jessica Vermeulen, Robin Carson, Pieter Sonneveld, Adrian Alegre Amor, Angelo Belotti, Lotfi Benboubker, Britta Besemer, Sevgi Besisik, Michele Cavo, Javier De La Rubia Comos, Meletios A. Dimopoulos, Chantal Doyen, Dominik Dytfeld, Monika Engelhardt, Thierry Facon, Roberto Foà, Hartmut Goldschmidt, Sebastian Grosicki, Roman Hajek, Guner Hayri Ozsan, Cyrille Hulin, Brian Iversen, Lionel Karlin, Stefan Knop, Marie-Christine Kyrtsonis, Juan Jose Lahuerta, Xavier Leleu, Carmen Martinez Chamorro, María-Victoria Mateos Manteca, Nathalie Meuleman, Monique Minnema, Massino Offidani, Albert Oriol Rocafiguera, Mustafa Pehlivan, Ludek Pour, Henk Th.J. Roerdink, Laura Rosinol Dacsh, Hans Salwender, Anargyros Symeonidis, Charlotte Toftmann Hansen, Tulin Tuglular, Ali Unal, Philip Vlummens, Filiz Vural, Ka Lung Wu, Sonja Zweegman
Přispěvatelé: Multiple Myeloma Research Foundation, Janssen Research and Development, Dimopoulos, MA, Terpos, E, Boccadoro, M, Delimpasi, S, Beksac, M, Katodritou, E, Moreau, P, Baldini, L, Symeonidis, A, Bila, J, Oriol, A, Mateos, MV, Einsele, H, Orfanidis, I, Ahmadi, T, Ukropec, J, Kampfenkel, T, Schecter, JM, Qiu, YP, Amin, H, Vermeulen, J, Carson, R, Sonneveld, P, Adrian Alegre Amor, Luca Baldini, Meral Beksac, Angelo Belotti, Lotfi Benboubker, Britta Besemer, Sevgi Besisik, Jelena Bila, Mario Boccadoro, Michele Cavo, Javier De La Rubia Comos, Sosana Delimpasi, Meletios A Dimopoulos, Chantal Doyen, Dominik Dytfeld, Monika Engelhardt, Thierry Facon, Roberto Foà, Hartmut Goldschmidt, Sebastian Grosicki, Roman Hajek, Guner Hayri Ozsan, Cyrille Hulin, Brian Iversen, Lionel Karlin, Eirini Katodritou, Stefan Knop, Marie-Christine Kyrtsonis, Juan Jose Lahuerta, Xavier Leleu, Carmen Martinez Chamorro, María-Victoria Mateos Manteca, Nathalie Meuleman, Monique Minnema, Philippe Moreau, Massino Offidani, Albert Oriol Rocafiguera, Mustafa Pehlivan, Ludek Pour, Henk Th J Roerdink, Laura Rosinol Dacsh, Hans Salwender, Pieter Sonneveld, Anargyros Symeonidis, Charlotte Toftmann Hansen, Tulin Tuglular, Ali Unal, Philip Vlummens, Filiz Vural, Ka Lung Wu, Sonja Zweegman, Hematology, CCA - Cancer Treatment and quality of life
Rok vydání: 2021
Předmět:
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
APOLLO Trial Investigators 2021, ' Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO) : an open-label, randomised, phase 3 trial ', The Lancet Oncology, vol. 22, no. 6, pp. 801-812 . https://doi.org/10.1016/S1470-2045(21)00128-5
LANCET ONCOLOGY
r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol
The Lancet. Oncology, 22(6), 801-812. Lancet Publishing Group
The Lancet Oncology, 22(6), 801-812. Lancet Publishing Group
ISSN: 1470-2045
DOI: 10.1016/S1470-2045(21)00128-5
Popis: Background: In a phase 1b study, intravenous daratumumab plus pomalidomide and dexamethasone induced a very good partial response or better rate of 42% and was well tolerated in patients with heavily pretreated multiple myeloma. We aimed to evaluate whether daratumumab plus pomalidomide and dexamethasone would improve progression-free survival versus pomalidomide and dexamethasone alone in patients with previously treated multiple myeloma. Methods: In this ongoing, open-label, randomised, phase 3 trial (APOLLO) done at 48 academic centres and hospitals across 12 European countries, eligible patients were aged 18 years or older, had relapsed or refractory multiple myeloma with measurable disease, had an Eastern Cooperative Oncology Group performance status of 0–2, had at least one previous line of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to one or more previous lines of antimyeloma therapy, and were refractory to lenalidomide if only one previous line of therapy was received. Patients were randomly assigned (1:1) by an interactive web-response system in a random block size of two or four to receive pomalidomide and dexamethasone alone or daratumumab plus pomalidomide and dexamethasone. Randomisation was stratified by number of previous lines of therapy and International Staging System disease stage. All patients received oral pomalidomide (4 mg, once daily on days 1–21) and oral dexamethasone (40 mg once daily on days 1, 8, 15, and 22; 20 mg for those aged 75 years or older) at each 28-day cycle. The daratumumab plus pomalidomide and dexamethasone group received daratumumab (1800 mg subcutaneously or 16 mg/kg intravenously) weekly during cycles 1 and 2, every 2 weeks during cycles 3–6, and every 4 weeks thereafter until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT03180736. Findings: Between June 22, 2017, and June 13, 2019, 304 patients (median age 67 years [IQR 60–72]; 161 [53%] men and 143 [47%] women) were randomly assigned to the daratumumab plus pomalidomide and dexamethasone group (n=151) or the pomalidomide and dexamethasone group (n=153). At a median follow-up of 16·9 months (IQR 14·4–20·6), the daratumumab plus pomalidomide and dexamethasone group showed improved progression-free survival compared with the pomalidomide and dexamethasone group (median 12·4 months [95% CI 8·3–19·3] vs 6·9 months [5·5–9·3]; hazard ratio 0·63 [95% CI 0·47–0·85], two-sided p=0·0018). The most common grade 3 or 4 adverse events were neutropenia (101 [68%] of 149 patients in the daratumumab plus pomalidomide and dexamethasone group vs 76 [51%] of 150 patients in the pomalidomide and dexamethasone group), anaemia (25 [17%] vs 32 [21%]), and thrombocytopenia (26 [17%] vs 27 [18%]). Serious adverse events occurred in 75 (50%) of 149 patients in the daratumumab plus pomalidomide and dexamethasone group versus 59 (39%) of 150 patients in the pomalidomide and dexamethasone group; pneumonia (23 [15%] vs 12 [8%] patients) and lower respiratory tract infection (18 [12%] vs 14 [9%]) were most common. Treatment-emergent deaths were reported in 11 (7%) patients in the daratumumab plus pomalidomide and dexamethasone group versus 11 (7%) patients in the pomalidomide and dexamethasone group. Interpretation: Among patients with relapsed or refractory multiple myeloma, daratumumab plus pomalidomide and dexamethasone reduced the risk of disease progression or death versus pomalidomide and dexamethasone alone and could be considered a new treatment option in this setting. Funding: European Myeloma Network and Janssen Research and Development.
European Myeloma Network and Janssen Research and Development.
Databáze: OpenAIRE
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