Manuela Gambella1, Paola Omedé1, Stefano Spada1, Vittorio Emanuele Muccio1, Milena Gilestro1, Elona Saraci1, Sara Grammatico2, Alessandra Larocca1, Concetta Conticello3, Annalisa Bernardini1, Barbara Gamberi4, Rossella Troia1, Anna Marina Liberati5, Massimo Offidani6, Alberto Rocci7,8, Antonio Palumbo1, Michele Cavo9, Pieter Sonneveld10, Mario Boccadoro1, Stefania Oliva1. 1. Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy. 2. Hematology Unit, Department of Cellular Biotechnologies and Hematology, Policlinico Umberto 1, "Sapienza" University, Rome, Italy. 3. Division of Hematology, Azienda Ospedaliero-Universitaria 'Policlinico-Vittorio Emanuele', Catania, Italy. 4. Hematology Unit, AUSL-IRCSS, Reggio Emilia, Italy. 5. Università degli Studi di Perugia, Perugia, Italy. 6. Hematology Clinic, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy. 7. Hematology Department, Manchester University National Health Service Foundation Trust, Manchester Royal Infirmary, Manchester, United Kingdom. 8. Faculty of Biology, Medicine, and Health, School of Medical Science, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom. 9. "Seragnoli" Institute of Hematology, Bologna University School of Medicine, Bologna, Italy. 10. Department of Hematology, Cancer Institute, Erasmus Medical Center, Rotterdam, the Netherlands.
Abstract
BACKGROUND: Minimal residual disease (MRD) is one of the most relevant prognostic factors in patients with multiple myeloma (MM); however, the impact of maintenance therapy on MRD levels remains unclear. Among patients with newly diagnosed MM (NDMM) who received lenalidomide maintenance until they developed disease progression, the role of MRD status as a predictor of progression-free survival (PFS) was evaluated by multiparameter flow cytometry (MFC) and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) analysis. METHODS: Seventy-three patients with NDMM enrolled in the RV-MM-EMN-441 (clinical trials.gov identifier, NCT01091831) and RV-MM-COOP-0556 (clinicaltrials.gov identifier, NCT01208766; European Myeloma Network EMN02/HO95 MM Trial) phase 3 trials who achieved at least a very good partial response after intensification/consolidation were included. The median patient age was 57 years (interquartile range, 53-61 years), and all patients received lenalidomide maintenance until they developed progression. MRD was evaluated on bone marrow after intensification/consolidation, after 6 courses of maintenance, and every 6 months thereafter until clinical relapse using both ASO-RQ-PCR (sensitivity, 10-5 ) and MFC (sensitivity, from 10-4 to 10-5 ). RESULTS: After intensification/consolidation, 33 of 72 patients (46%) achieved a molecular complete response (m-CR), and 44 of 70 (63%) achieved a flow complete response (flow-CR). Almost 27% of patients who were MRD-positive after consolidation became MRD-negative during maintenance. After a median follow-up of 38 months, PFS was prolonged in patients who achieved negative MRD status during maintenance according to results from both ASO-RQ-PCR analysis (hazard ratio, 0.29; 95% confidence interval, 0.14-0.62; P = .0013) and MFC (hazard ratio, 0.19; 95% confidence interval, 0.09-0.41; P < .001). The impact of negative MRD status on PFS was similar in all subgroups (ASCT and no-ASCT; International Staging System stages I, II, and III; high-risk and standard-risk cytogenetics), and the two techniques were highly correlated. CONCLUSIONS: MRD status is a stronger predictor of PFS than standard risk factors, and lenalidomide maintenance further increases the rate of negative MRD results.
BACKGROUND: Minimal residual disease (MRD) is one of the most relevant prognostic factors in patients with multiple myeloma (MM); however, the impact of maintenance therapy on MRD levels remains unclear. Among patients with newly diagnosed MM (NDMM) who received lenalidomide maintenance until they developed disease progression, the role of MRD status as a predictor of progression-free survival (PFS) was evaluated by multiparameter flow cytometry (MFC) and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) analysis. METHODS: Seventy-three patients with NDMM enrolled in the RV-MM-EMN-441 (clinical trials.gov identifier, NCT01091831) and RV-MM-COOP-0556 (clinicaltrials.gov identifier, NCT01208766; European Myeloma Network EMN02/HO95 MM Trial) phase 3 trials who achieved at least a very good partial response after intensification/consolidation were included. The median patient age was 57 years (interquartile range, 53-61 years), and all patients received lenalidomide maintenance until they developed progression. MRD was evaluated on bone marrow after intensification/consolidation, after 6 courses of maintenance, and every 6 months thereafter until clinical relapse using both ASO-RQ-PCR (sensitivity, 10-5 ) and MFC (sensitivity, from 10-4 to 10-5 ). RESULTS: After intensification/consolidation, 33 of 72 patients (46%) achieved a molecular complete response (m-CR), and 44 of 70 (63%) achieved a flow complete response (flow-CR). Almost 27% of patients who were MRD-positive after consolidation became MRD-negative during maintenance. After a median follow-up of 38 months, PFS was prolonged in patients who achieved negative MRD status during maintenance according to results from both ASO-RQ-PCR analysis (hazard ratio, 0.29; 95% confidence interval, 0.14-0.62; P = .0013) and MFC (hazard ratio, 0.19; 95% confidence interval, 0.09-0.41; P < .001). The impact of negative MRD status on PFS was similar in all subgroups (ASCT and no-ASCT; International Staging System stages I, II, and III; high-risk and standard-risk cytogenetics), and the two techniques were highly correlated. CONCLUSIONS: MRD status is a stronger predictor of PFS than standard risk factors, and lenalidomide maintenance further increases the rate of negative MRD results.
Authors: Rafael Alonso; María-Teresa Cedena; Sandy Wong; Nina Shah; Rafael Ríos-Tamayo; José M Moraleda; Javier López-Jiménez; Cristina García; Natasha Bahri; Antonio Valeri; Ricardo Sánchez; Luis Collado-Yurrita; Thomas Martin; Jeffrey Wolf; Juan-José Lahuerta; Joaquín Martínez-López Journal: Blood Adv Date: 2020-05-26
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