Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma
Open accessAbstract
Purpose: Continuous therapy (CT) prolongs progression-free survival 1 (PFS1; time from random assignment until the first progression or death), but chemotherapy-resistant relapse may negatively impact overall survival (OS). Progression-free survival 2 (PFS2; time from random assignment until the second progression or death) may represent an additional tool to estimate outcome. This study evaluates the benefit of novel agent–based CT versus fixed duration of therapy (FDT) in patients with newly diagnosed myeloma. Methods: We included patients enrolled onto three phase III trials that randomly assigned patients to novel agent–based CT versus FDT. Primary analyses were restricted to the intent-to-treat population eligible for CT (patients progression free and alive at 1 year after random assignment). Primary end points were PFS1, PFS2, and OS. All hazard ratios (HRs) and 95% CIs were adjusted for several potential confounders using Cox models. Results: In the pooled analysis of the three trials, 604 patients were randomly assigned to CT and 614 were assigned to FDT. Median follow-up was 52 months. In the intent-to-treat CT population, CT (n = 417), compared with FDT (n = 410), significantly improved PFS1 (median, 32 v 16 months, respectively; HR, 0.47; 95% CI, 0.40 to 0.56; P < .001), PFS2 (median, 55 v 40 months, respectively; HR, 0.61; 95% CI, 0.50 to 0.75; P < .001), and OS (4-year OS, 69% v 60%, respectively; HR, 0.69; 95% CI, 0.54 to 0.88; P = .003). Conclusion: In this pooled analysis, CT significantly improved PFS1, PFS2, and OS. The improvement in PFS2 suggests that the benefit reported during first remission is not cancelled by a shorter second remission. PFS2 is a valuable end point to estimate long-term clinical benefit and should be included in future trials.
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Pomalidomide has demonstrated efficacy in around a third of patients with lenalidomide-refractory MM.
“The success of lenalidomide led to the development of pomalidomide, which has demonstrated efficacy in around a third of patients with lenalidomide-refractory MM42–44.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [43]
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Cites
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Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide
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- Authors
- Palumbo, A., Gay, F., Cavallo, F., Di Raimondo, F., Larocca, A., Hardan, I., Nagler, A., Petrucci, M. T., Hajek, R., Pezzatti, S., Delforge, M., Patriarca, F., Donato, F., Cerrato, C., Nozzoli, C., Yu, Z., Boccadifuoco, L., Caravita, T., Benevolo, G., Guglielmelli, T., Vincelli, D., Jacques, C., Dimopoulos, M. A., Ciccone, G., Musto, P., Corradini, P., Cavo, M., & Boccadoro, M.
- Affiliations
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- Antonio Palumbo, Francesca Gay, Federica Cavallo, Alessandra Larocca, Francesca Donato, Chiara Cerrato, Luana Boccadifuoco, and Mario Boccadoro, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino; Giulia Benevolo, S.C. Ematologia A.O. Città della Salute e della Scienza di Torino; Tommasina Guglielmelli, University of Turin and San Luigi Hospital; Giovannino Ciccone, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino and CPO...
- University of Udine (IT)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2015-10-20
- Volume
- 33
- Issue
- 30
- Pages
- 3459-3466
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2107384529
- Cited by
- 150
- References
- 31
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 12 · 2022: 14 · 2021: 15 · 2020: 15 · 2019: 18 · 2018: 22 · 2017: 20 · 2016: 19 · 2015: 3
- FWCI
- 16.74
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Institutional Research Information System (University of Udine) (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Lirias (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- Celgene
- Cilag
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- multiple myeloma, newly diagnosed multiple myeloma, continuous treatment, progression-free survival, overall survival, second remission, chemoresistance
- MeSH terms
- Bortezomib, Lenalidomide, Aged, Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Drug Administration Schedule, Female, Humans, Male, Melphalan, Middle Aged, Multiple Myeloma, Prednisone, Thalidomide, Disease-Free Survival
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