ArticleBlood2023
High-dose melphalan treatment significantly increases mutational burden at relapse in multiple myeloma.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Measurable Residual Disease-Guided Therapy in Newly Diagnosed Myeloma.The New England journal of medicine · 2025Trial
- Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma.The New England journal of medicine · 2022Trial
- Breaking the Balance: Baseline Oxidative Stress and DNA Repair Capacity in Multiple Myeloma Therapy.Cancers · 2026Article
- Clonal hematopoiesis in patients with cancer and cancer survivors: From clonal burden to cardiovascular diseases.Cancer · 2026Review
- The Evolving Role of Genomic Technologies in Multiple Myeloma: Implications for Diagnosis, Risk Stratification and Resistance.Molecular diagnosis & therapy · 2026Review
- Is Less "Sufficient" and "Safe" in the MRD Era - Outcomes of Autologous Stem-Cell Transplant as per Melphalan Dose in Patients with Multiple Myeloma.Blood cancer journal · 2026Article
- Second Primary Malignancies Post Autologous Stem-cell Transplant in Multiple Myeloma from India - Knowing the Unknown.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2026Article
- Management of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplantation: position statement of the Medical and Scientific Advisory Group of Myeloma Australia.Internal medicine journal · 2025Article
- Article
- Emerging T-cell lymphomas after CAR T-cell therapy.Leukemia · 2025Review
- Multiomic profiling of T cell lymphoma after therapy with anti-BCMA CAR T cells and GPRC5D-directed bispecific antibody.Nature medicine · 2025Article
- Article
- New horizons in our understanding of precursor multiple myeloma and early interception.Nature reviews. Cancer · 2024Review
- Rising Prevalence of Low-FrequencyCurrent issues in molecular biology · 2024Article
- Acute Erythroid Leukemia Post-Chemo-Radiotherapy and Autologous Stem Cell Transplantation Due to Multiple Myeloma: Tracing the Paths to Leukemic Transformation.International journal of molecular sciences · 2024Article
- Article
- Article
- Advances and challenges in anti-cancer vaccines for multiple myeloma.Frontiers in immunology · 2024Review
- Autologous hematopoietic stem cell transplantation for multiple myeloma in the age of CAR T cell therapy.Frontiers in oncology · 2024Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
High-dose melphalan (HDM) improves progression-free survival in multiple myeloma (MM), yet melphalan is a DNA-damaging alkylating agent; therefore, we assessed its mutational effect on surviving myeloma cells by analyzing paired MM samples collected at diagnosis and relapse in the IFM 2009 study. We performed deep whole-genome sequencing on samples from 68 patients, 43 of whom were treated with RVD (lenalidomide, bortezomib, and dexamethasone) and 25 with RVD + HDM. Although the number of mutations was similar at diagnosis in both groups (7137 vs 7230; P = .67), the HDM group had significantly more mutations at relapse (9242 vs 13 383, P = .005). No change in the frequency of copy number alterations or structural variants was observed. The newly acquired mutations were typically associated with DNA damage and double-stranded breaks and were predominantly on the transcribed strand. A machine learning model, using this unique pattern, predicted patients who would receive HDM with high sensitivity, specificity, and positive prediction value. Clonal evolution analysis showed that all patients treated with HDM had clonal selection, whereas a static progression was observed with RVD. A significantly higher percentage of mutations were subclonal in the HDM cohort. Intriguingly, patients treated with HDM who achieved complete remission (CR) had significantly more mutations at relapse yet had similar survival rates as those treated with RVD who achieved CR. This similarity could have been due to HDM relapse samples having significantly more neoantigens. Overall, our study identifies increased genomic changes associated with HDM and provides rationale to further understand clonal complexity.
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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.