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Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA

Autores: Cavo, M. (Autor de correspondencia); San Miguel Izquierdo, Jesús; Usmani, S. Z.; Weisel, K.; Dimopoulos, M. A.; Avet-Loiseau, H.; Paiva, Bruno; Bahlis, N. J.; Plesner, T.; Hungria, V.; Moreau, P.; Mateos, M. V.; Perrot, A.; Iida, S.; Facon, T.; Kumar, S.; van de Donk, N. W. C. J.; Sonneveld, P.; Spencer, A.; Krevvata, M.; Heuck, C.; Wang, J.; Ukropec, J.; Kobos, R.; Sun, S.; Qi, M.; Munshi, N.
Título de la revista: BLOOD
ISSN: 0006-4971
Volumen: 139
Número: 6
Páginas: 835 - 844
Fecha de publicación: 2022
We explored minimal residual disease (MRD) in relapsed/refractory multiple myeloma (RRMM) and transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM) using data from 4 phase 3 studies (POLLUX, CASTOR, ALCYONE, and MAIA). Each study previously demonstrated that daratumumab-based therapies improved MRD negativity rates and reduced the risk of disease progression or death by approximately half vs standards of care. We conducted a large-scale pooled analysis for associations between patients achieving complete response or better (>= CR) with MRD-negative status and progression-free survival (PFS). MRD was assessed via next-generation sequencing (10(-5) sensitivity threshold). Patient-level data were pooled from all 4 studies and for patients with TIE NDMM and patients with RRMM who received <= 2 prior lines of therapy (<= 2 PL). PFS was evaluated by response and MRD status. Median follow-up (months) was 54.8 for POLLUX, 50.2 for CASTOR, 40.1 for ALCYONE, and 36.4 for MAIA. Patients who achieved >= CR and MRD negativity had improved PFS vs those who failed to reach CR or were MRD positive (TIE NDMM and RRMM hazard ratio [HR] 0.20, P < .0001; TIE NDMM and RRMM <= 2 PL HR 0.20, P < .0001). This benefit occurred irrespective of therapy or disease setting. A time-varying Cox proportional hazard model confirmed that >= CR with MRD negativity was associated with improved PFS. Daratumumab-based treatment was associated with more patients reaching >= CR and MRD negativity. These findings represent the first large-scale analysis with robust methodology to support >= CR with MRD negativity as a prognostic factor for PFS in RRMM and TIE NDMM.