TY - JOUR
T1 - Prognostic value of minimal residual disease negativity in myeloma
T2 - combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA
AU - Cavo, Michele
AU - San-Miguel, Jesus
AU - Usmani, Saad Z.
AU - Weisel, Katja
AU - Dimopoulos, Meletios A.
AU - Avet-Loiseau, Hervé
AU - Paiva, Bruno
AU - Bahlis, Nizar J.
AU - Plesner, Torben
AU - Hungria, Vania
AU - Moreau, Philippe
AU - Mateos, Maria Victoria
AU - Perrot, Aurore
AU - Iida, Shinsuke
AU - Facon, Thierry
AU - Kumar, Shaji
AU - van de Donk, Niels W.C.J.
AU - Sonneveld, Pieter
AU - Spencer, Andrew
AU - Krevvata, Maria
AU - Heuck, Christoph
AU - Wang, Jianping
AU - Ukropec, Jon
AU - Kobos, Rachel
AU - Sun, Steven
AU - Qi, Mia
AU - Munshi, Nikhil
N1 - Funding Information:
The authors thank the patients, volunteers, co-investigators, staff members at the trial sites, and clinical site coordinators who participated in the POLLUX, CASTOR, ALCYONE, and MAIA studies. They also thank representatives of the sponsor who were involved in data collection and analysis, as well as Charlotte Majerczyk (Cello Health Communications/MedErgy) for medical writing and editorial assistance, which was funded by Janssen Global Services. The studies were supported by Janssen Research & Development, LLC.
Publisher Copyright:
© 2022 American Society of Hematology
PY - 2022/2/10
Y1 - 2022/2/10
N2 - 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. These trials were registered at www.clinicaltrials.gov as #NCT02076009, #NCT02136134, #NCT02195479, and #NCT02252172.
AB - 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. These trials were registered at www.clinicaltrials.gov as #NCT02076009, #NCT02136134, #NCT02195479, and #NCT02252172.
UR - http://www.scopus.com/inward/record.url?scp=85124181097&partnerID=8YFLogxK
U2 - 10.1182/blood.2021011101
DO - 10.1182/blood.2021011101
M3 - Article
C2 - 34289038
AN - SCOPUS:85124181097
SN - 0006-4971
VL - 139
SP - 835
EP - 844
JO - Blood
JF - Blood
IS - 6
ER -