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

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...

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Published in:	Blood Vol. 139; no. 6; p. 835
Main Authors:	Cavo, Michele, San-Miguel, Jesus, Usmani, Saad Z, Weisel, Katja, Dimopoulos, Meletios A, Avet-Loiseau, Hervé, Paiva, Bruno, Bahlis, Nizar J, Plesner, Torben, Hungria, Vania, Moreau, Philippe, Mateos, Maria-Victoria, Perrot, Aurore, Iida, Shinsuke, Facon, Thierry, Kumar, Shaji, van de Donk, Niels W C J, Sonneveld, Pieter, Spencer, Andrew, Krevvata, Maria, Heuck, Christoph, Wang, Jianping, Ukropec, Jon, Kobos, Rachel, Sun, Steven, Qi, Mia, Munshi, Nikhil
Format:	Journal Article
Language:	English
Published:	United States 10.02.2022
Subjects:	Aged Antibodies, Monoclonal - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Disease-Free Survival Humans Multiple Myeloma - diagnosis Multiple Myeloma - drug therapy Neoplasm Recurrence, Local - diagnosis Neoplasm Recurrence, Local - drug therapy Neoplasm, Residual - diagnosis Neoplasm, Residual - drug therapy Prognosis Progression-Free Survival Treatment Outcome
ISSN:	1528-0020, 1528-0020
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	1528-0020 1528-0020
DOI:	10.1182/blood.2021011101