TY - JOUR
T1 - MRD dynamics during maintenance for improved prognostication of 1280 patients with myeloma in the TOURMALINE-MM3 and -MM4 trials
AU - Paiva, Bruno
AU - Manrique, Irene
AU - Dimopoulos, Meletios A.
AU - Gay, Francesca
AU - Min, Chang-Ki
AU - Zweegman, Sonja
AU - Špička, Ivan
AU - Teipel, Raphael
AU - Mateos, María-Victoria
AU - Giuliani, Nicola
AU - Cavo, Michele
AU - Hopkins, Christine Rojas
AU - Fu, Weijun
AU - Suryanarayan, Kaveri
AU - Vorog, Alexander
AU - Li, Cong
AU - Wang, Bingxia
AU - Estevam, Jose
AU - Labotka, Richard
AU - Dash, Ajeeta B.
N1 - Funding Information: This work was supported by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Editorial support was provided by Victoria Enwemadu of Takeda Pharmaceuticals USA, Inc., Lexington, MA; and medical writing support for the development of this manuscript, under the direction of the authors, was provided by Philippa Lloyd, BSc, and Steve Hill, PhD, of Ashfield MedComms, an Inizio Company, funded by Takeda Pharmaceuticals USA, Inc., Lexington, MA and complied with Good Publication Practice (GPP) guidelines (DeTora LM et al, Ann Intern Med 2022;175:1298-1304). Publisher Copyright: © 2022 The American Society of Hematology
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85143285106&partnerID=8YFLogxK
U2 - https://doi.org/10.1182/blood.2022016782
DO - https://doi.org/10.1182/blood.2022016782
M3 - Article
C2 - 36130300
SN - 0006-4971
JO - Blood
JF - Blood
ER -