Manuel Neves ^1* Rita Gerivaz ² Graça Esteves ³ Rui Bergantim ⁴ Gisela Ferreira ⁵ Henrique Coelho ⁶ Celina Afonso ⁷ Delfim Duarte ⁸ Anabela Neves ⁹ Helena Matos Silva ¹⁰ Joana Caetano ¹ Rita Jaime ¹¹ Catarina Geraldes ¹² Paulo Lucio ¹

• ¹ Champalimaud Research, Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal
• ² Hematology Unit, Unidade Local de saúde Almada-Seixal, Lisboa, Portugal
• ³ Hematology & Transplantation Unit, Unidade Local de saúde Santa Maria, Lisboa, Portugal, Lisboa, Portugal
• ⁴ Hematology Department, Unidade Local de Saúde de S. João, Porto, Portugal, Porto, Portugal
• ⁵ Hematology Department, Unidade Local de Saúde da Região de Aveiro, Aveiro, Portugal, Aveiro, Portugal
• ⁶ Hemato-Oncology Unit, Unidade Local de Saúde de Matosinhos, Gaia, Portugal, Matosinhos, Portugal
• ⁷ Hematology Unit, Unidade Local de Saúde de Lisboa Ocidental, Lisboa, Portugal, Lisboa, Portugal
• ⁸ Department of Hematology and Bone Marrow Transplantation, Instituto Português de Oncologia Porto Francisco Gentil, Porto, Portugal, Porto, Portugal
• ⁹ Hemato-Oncology Unit, Unidade Local de Saúde da Arrábida, Setubal, Portugal, Setúbal, Portugal
• ¹⁰ Hemato-Oncology Unit, Unidade Local de Saúde de Viseu Dão-Lafões Viseu, Viseu, Portugal, Viseu, Portugal
• ¹¹ Janssen-Cilag Farmacêutica, Oeiras, Portugal
• ¹² Hematology Department, Unidade Local de Saúde de Coimbra, Coimbra, Portugal, Coimbra, Portugal

Multiple myeloma (MM) is an incurable hematologic malignancy, and even though the complete response (CR) rate has been growing, a high percentage of patients continues to relapse. Recent research showed that most relapses may be related to the persistence of measurable residual disease (MRD). In this study, we intended to evaluate the MRD status in MM patients who reached CR in their second or third lines of treatment. This was a cross-sectional, multicentre, non-interventional study to describe the MRD status in patients with relapsed or refractory MM (rrMM), with documented CR; adult male and female patients, from 11 Portuguese sites, in their second or third line of treatment were included. Bone marrow MRD was assessed through next-generation flow cytometry (NGF) technology.Among the 68 subjects who gave informed consent, 48 were considered eligible for the study. Of the 48 subjects with confirmed CR, 31 (64.6%) had undetectable MRD levels. The incidence of undetectable MRD was lower in International Staging System (ISS) III patients compared with ISS I/II patients (60% vs. 70.8%; p = 0.45), and lower in patients treated without daratumumab-containing regimens compared with those treated with daratumumab-containing regimens (57.1% vs. 75.0%; p = 0.30). Notably, despite the small sample size, the incidence of undetectable MRD was significantly lower in patients with high-risk cytogenetics compared to those with standard risk (33.3% vs. 76.0%; p = 0.04). Our results highlight the possibility of achieving undetectable MRD in the rrMM setting, especially in earlier stages and with highly effective protocols. We expect that this work leverages the implementation of larger real-world evidence studies in rrMM patients, in which MRD may also be defined as a primary endpoint.