Chiara Cerrato1, Francesco Di Raimondo2, Lorenzo De Paoli3, Stefano Spada1, Francesca Patriarca4, Claudia Crippa5, Roberto Mina1, Tommasina Guglielmelli6, Dina Ben-Yehuda7, Daniela Oddolo1, Chiara Nozzoli8, Emanuele Angelucci9, Nicola Cascavilla10, Rita Rizzi11, Stefano Rocco12, Luca Baldini13, Elena Ponticelli1, Magda Marcatti14, Clotilde Cangialosi15, Tommaso Caravita16, Giulia Benevolo17, Roberto Ria18, Arnon Nagler19, Pellegrino Musto20, Paola Tacchetti21, Paolo Corradini22, Massimo Offidani23, Antonio Palumbo1,24, Maria Teresa Petrucci25, Mario Boccadoro1, Francesca Gay26. 1. Myeloma Unit, Division of Hematology, University of Torino, Azienda-Ospedaliero Universitaria Città della Salute e della Scienza di Torino, via Genova 3, 10126, Torino, Italy. 2. UOC Ematologia, Azienda Policlinico-OVE, University of Catania, Catania, Italy. 3. Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Maggiore Hospital, Novara, Italy. 4. Dipartimento di Medicina, Università di Udine, Udine, Italy. 5. Divisione di Ematologia, Spedali Civili Brescia, Brescia, Italy. 6. Department of Clinical and Biological Sciences, Orbassano, TO, Italy. 7. Hematology Department, Hadassah Medical Center, Jerusalem, Israel. 8. SODc Terapie cellulari e medicina trasfusionale AOUC Careggi, Firenze, Italy. 9. IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. 10. Hematology "Casa Sollievo della Sofferenza" Hospital IRCCS, San Giovanni Rotondo, FG, Italy. 11. Section of Hematology with Transplantation, Department of Emergency and Organ Transplantation, University of Bari Medical School, Bari, Italy. 12. UOSC Ematologia con Trapianto - AORN Cardarelli Napoli, Napoli, Italy. 13. Department of Oncology and Hemato-oncology, University of Milan, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano, Italy. 14. U.O. Ematologia e Trapianto di Midollo, IRCCS Ospedale San Raffaele, Milano, Italy. 15. Ospedali Riuniti Villa Sofia-Cervello, Unità Operativa di Ematologia I e UTMO, Palermo, Italy. 16. UOC Ematologia Ospedale S. Eugenio ASL RM2, Roma, Italy. 17. SC Hematology, Città della Salute e della Scienza Hospital, Torino, Italy. 18. University of Bari "Aldo Moro" Medical School, Department of Biomedical Science, Internal Medicine "G. Baccelli", Policlinico, Bari, Italy. 19. Hematology Division, Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel. 20. Scientific Direction, IRCCS Referral Cancer Center of Basilicata, Rionero in Vulture, PZ, Italy. 21. "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine, Bologna University School of Medicine, Bologna, Italy. 22. Department of Oncology and Hematology, University of Milano, Milano, Italy. 23. Clinica di Ematologia, AOU Ospedali Riuniti di Ancona, Loc. Torrette, Ancona, Italy. 24. Takeda, Zürich, Switzerland. 25. Hematology, "Sapienza" University of Rome, Roma, Italy. 26. Myeloma Unit, Division of Hematology, University of Torino, Azienda-Ospedaliero Universitaria Città della Salute e della Scienza di Torino, via Genova 3, 10126, Torino, Italy. fgay@cittadellasalute.to.it.
Abstract
PURPOSE: Maintenance demonstrated to improve survival in newly diagnosed multiple myeloma (NDMM) patients and the achievement of complete response (CR) is a strong predictor of survival. Nevertheless, the role of maintenance according to response after induction/consolidation has not been investigated so far. To evaluate the impact of maintenance according to response, we pooled together and retrospectively analyzed data from 955 NDMM patients enrolled in two trials (GIMEMA-MM-03-05 and RV-MM-PI-209). METHODS: Primary endpoints were progression-free survival (PFS)1, PFS2 and overall survival (OS) of CR patients randomized to maintenance and no maintenance. Secondary endpoints were PFS1, PFS2 and OS in very good partial response/partial response (VGPR/PR) patients. RESULTS: Overall, 213 patients obtained CR after induction/consolidation, 118 received maintenance and 95 no maintenance. In patients achieving CR, maintenance significantly improved PFS1 (HR 0.50, P < 0.001), PFS2 (HR 0.58, P 0.02) and OS (HR 0.51, P 0.02) compared with no maintenance; the advantage was maintained across all the analyzed subgroups according to age, International Staging System (ISS) stage, cytogenetic profile and treatment. Similar features were seen in VGPR/PR patients. CONCLUSION:Maintenance prolonged survival in CR and in VGPR/PR patients. The benefit in CR patients suggests the importance of continuing treatment in patients with chemo-sensitive disease. TRIAL REGISTRATION: The two source studies are registered at ClinicalTrials.gov: identification numbers NCT01063179 and NCT00551928.
RCT Entities:
PURPOSE: Maintenance demonstrated to improve survival in newly diagnosed multiple myeloma (NDMM) patients and the achievement of complete response (CR) is a strong predictor of survival. Nevertheless, the role of maintenance according to response after induction/consolidation has not been investigated so far. To evaluate the impact of maintenance according to response, we pooled together and retrospectively analyzed data from 955 NDMM patients enrolled in two trials (GIMEMA-MM-03-05 and RV-MM-PI-209). METHODS: Primary endpoints were progression-free survival (PFS)1, PFS2 and overall survival (OS) of CR patients randomized to maintenance and no maintenance. Secondary endpoints were PFS1, PFS2 and OS in very good partial response/partial response (VGPR/PR) patients. RESULTS: Overall, 213 patients obtained CR after induction/consolidation, 118 received maintenance and 95 no maintenance. In patients achieving CR, maintenance significantly improved PFS1 (HR 0.50, P < 0.001), PFS2 (HR 0.58, P 0.02) and OS (HR 0.51, P 0.02) compared with no maintenance; the advantage was maintained across all the analyzed subgroups according to age, International Staging System (ISS) stage, cytogenetic profile and treatment. Similar features were seen in VGPR/PR patients. CONCLUSION: Maintenance prolonged survival in CR and in VGPR/PR patients. The benefit in CR patients suggests the importance of continuing treatment in patients with chemo-sensitive disease. TRIAL REGISTRATION: The two source studies are registered at ClinicalTrials.gov: identification numbers NCT01063179 and NCT00551928.
Authors: Bruno Paiva; Norma C Gutiérrez; Laura Rosiñol; María-Belén Vídriales; María-Ángeles Montalbán; Joaquín Martínez-López; María-Victoria Mateos; María-Teresa Cibeira; Lourdes Cordón; Albert Oriol; María-José Terol; María-Asunción Echeveste; Raquel de Paz; Felipe de Arriba; Luis Palomera; Javier de la Rubia; Joaquín Díaz-Mediavilla; Anna Sureda; Ana Gorosquieta; Adrian Alegre; Alejandro Martin; Miguel T Hernández; Juan-José Lahuerta; Joan Bladé; Jesús F San Miguel Journal: Blood Date: 2011-11-29 Impact factor: 22.113
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Authors: Meletios A Dimopoulos; Andrzej J Jakubowiak; Philip L McCarthy; Robert Z Orlowski; Michel Attal; Joan Bladé; Hartmut Goldschmidt; Katja C Weisel; Karthik Ramasamy; Sonja Zweegman; Andrew Spencer; Jeffrey S Y Huang; Jin Lu; Kazutaka Sunami; Shinsuke Iida; Wee-Joo Chng; Sarah A Holstein; Alberto Rocci; Tomas Skacel; Richard Labotka; Antonio Palumbo; Kenneth C Anderson Journal: Blood Cancer J Date: 2020-02-13 Impact factor: 11.037