Trial reportEuropean journal of haematology2020
Clinical benefit of ixazomib plus lenalidomide-dexamethasone in myeloma patients with non-canonical NF-κB pathway activation.
Trial report in European journal of haematology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01564537 (A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral Ixazomib), which is not on this map. Cited by 16 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral Ixazomib (MLN9708) Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma
Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 19 citations in OpenAlex.
- Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Pooled it
- Next-generation sequencing for guiding matched targeted therapies in people with relapsed or metastatic cancer.The Cochrane database of systematic reviews · 2025Pooled it
- Clinical benefit of ixazomib plus lenalidomide-dexamethasone in myeloma patients with non-canonical NF-κB pathway activation.European journal of haematology · 2020Trial
- Genetic architecture of multiple myeloma: From somatic alterations to germline susceptibility and clinical implications.Translational oncology · 2026Review
- Targeting the nuclear factor kappa B pathway for the medical management of intervertebral disc degeneration.Frontiers in neuroscience · 2026Review
- NF-κB in inflammation and cancer.Cellular & molecular immunology · 2025Review
- The Bidirectional Interaction Between NF-Journal of immunology research · 2025Review
- NF-κB role on tumor proliferation, migration, invasion and immune escape.Cancer gene therapy · 2024Review
- Descriptive Analysis of Adverse Events Reported for New Multiple Myeloma Medications Using FDA Adverse Event Reporting System (FAERS) Databases from 2015 to 2022.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Next-Generation Therapies for Multiple Myeloma.Annual review of cancer biology · 2024Article
- Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.Cancer medicine · 2024Article
- Dynamic modulation of the non-canonical NF-κB signaling pathway for HIV shock and kill.Frontiers in cellular and infection microbiology · 2024Review
- Review
- NF-κB signaling in inflammation and cancer.MedComm · 2021Review
- Cysteinyl-specialized proresolving mediators link resolution of infectious inflammation and tissue regeneration via TRAF3 activation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Efficacy Analysis of Bortezomib Combined with Lenalidomide in Newly Diagnosed Multiple Myeloma with 1q21 Gain/Amp.Technology in cancer research & treatmentArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesEvaluating potential relationships between progression-free survival (PFS) and tumor gene expression patterns and mutational status was an exploratory objective of the phase 3 TOURMALINE-MM1 study (NCT01564537) of ixazomib-lenalidomide-dexamethasone (IRd) vs placebo-Rd in 722 patients with relapsed/refractory multiple myeloma (MM).
methodsWe utilized gene expression and mutation data from screening bone marrow aspirates to identify tumors with non-canonical nuclear factor-κB (NF-κB) signaling pathway activation.
resultsDNA/RNA sequencing data were available for 339 (47.0%)/399 (55.2%) patients; 49/339 (14.5%) patients had non-canonical NF-κB pathway gene mutations (tumor-necrosis-factor receptor-associated factor 2, 3 [TRAF2, TRAF3], baculoviral-inhibitor-of-apoptosis repeat-containing 2/3 [BIRC2/3]), and PFS was significantly longer with IRd vs placebo-Rd in these patients (hazard ratio [HR] 0.23). In patients with lower TRAF3 expression (median not reached vs 11 months, HR 0.47) and higher NF-κB-inducing kinase (NIK) expression (median not reached vs 14 months, HR 0.45), both associated with non-canonical NF-κB pathway activation, PFS was significantly longer with IRd vs placebo-Rd. TRAF3 expression was decreased in patients harboring t(4;14) and 1q21 amplification, suggesting increased non-canonical NF-κB pathway activation.
conclusionsAdding ixazomib to Rd provides clinical benefit in MM tumors with increased non-canonical NF-κB pathway activity. This is a potential mechanism for activity in 1q21 amplified high-risk tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.