Measurable residual disease (MRD) evaluation may help to guide treatment duration in multiple myeloma (MM). Paradoxically, limited longitudinal data exist on MRD during maintenance. We investigated the prognostic value of MRD dynamics in 1280 transplant-eligible and -ineligible patients from the TOURMALINE-MM3 and -MM4 randomized placebo-controlled phase 3 studies of 2-year ixazomib maintenance. MRD status at randomization showed independent prognostic value (median progression-free survival [PFS], 38.6 vs 15.6 months in MRD- vs MRD+ patients; HR, 0.47). However, MRD dynamics during maintenance provided more detailed risk stratification. A 14-month landmark analysis showed prolonged PFS in patients converting from MRD+ to MRD- status vs those with persistent MRD+ status (76.8% vs 27.6% 2-year PFS rates). Prolonged PFS was observed in patients with sustained MRD- status vs those converting from MRD- to MRD+ status (75.0% vs 34.2% 2-year PFS rates). Similar results were observed at a 28-month landmark analysis. Ixazomib maintenance vs placebo improved PFS in patients who were MRD+ at randomization (median, 18.8 vs 11.6 months; HR, 0.65) or at the 14-month landmark (median, 16.8 vs 10.6 months; HR, 0.65); no difference was observed in patients who were MRD-. This is the largest MM population undergoing yearly MRD evaluation during maintenance reported to date. We demonstrate the limited prognostic value of a single-time point MRD evaluation, because MRD dynamics over time substantially impact PFS risk. These findings support MRD- status as a relevant end point during maintenance and confirm the increased progression risk in patients converting to MRD+ from MRD- status. These trials were registered at www.clinicaltrials.gov as #NCT02181413 and #NCT02312258.

Clínica Bupa Reñaca Universidad de Valparaíso Viña del Mar Valparaíso Chile

Clinica Universidad de Navarra Centro de Investigación Médica Aplicada Pamplona Spain

Department of Hematology Amsterdam University Medical Center VU University Amsterdam Cancer Center Amsterdam Amsterdam The Netherlands

Department of Hematology Charles University Prague Czech Republic

Department of Hematology Shanghai 4th People's Hospital School of Medicine Tongji University Shanghai China

Department of Hematology Shanghai Changzheng Hospital Shanghai China

Department of Internal Medicine Seoul St Mary's Hospital Catholic University of Korea Seoul South Korea

Department of Oncology and Hematology Azienda Ospedaliero Universitaria City of Health and Science of Turin Turin Italy

Hematology and Medical Oncology Department of Clinical Therapeutics School of Medicine National and Kapodistrian University of Athens Athens Greece

IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Università di Bologna Bologna Italy

Medizinische Klinik und Poliklinik 1 Universitätsklinikum TU Dresden Dresden Germany

Myeloma Unit Department of Clinical and Experimental Medicine University of Parma and Ematologia e CTMO Azienda Ospedaliero Universitaria di Parma Parma Italy

Takeda Development Center Americas Lexington MA

University Hospital of Salamanca CIC IBMCC Salamanca Spain

Blood. 2023 Feb 9;141(6):557-558. doi: 10.1182/blood.2022018394. PubMed

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ClinicalTrials.gov
NCT02312258, NCT02181413