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Blood Adv. 2024 Feb 13;8(3):703-707 doi: 10.1182/bloodadvances.2023011601.
POPULATION:
Adults from a single centre in USA with newly diagnosed multiple myeloma, enrolled in the Total Therapy (TT) IIIB trial between 2006 and 2008, (n=177) INTERVENTION:Bortezomib incorporated into tandem melphalan-based hematopoietic stem cell transplantation with dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide for induction/consolidation and bortezomib, lenalidomide, and dexamethasone (VRD) for maintenance. Three years of VRD maintenance (TT IIIB, n=177) COMPARISON:Comparison cohort received one year of bortezomib, thalidomide, and dexamethasone followed by two years of thalidomide and dexamethasone (TD) maintenance (TT IIIA group) OUTCOME:15-year progression free survival (PFS) in TTIIIB was 27.9%. Median PFS was better in Gene expression profile (GEP)-defined low-risk patients at 7.8 years and in international stage system stage I patients at 8.7 years. Overall, median overall survival (OS) was 9.1 years, and 15-year OS was 35.9%. GEP-defined low-risk patients' median OS was 11.2 years, and that of GEP-defined high-risk patients was 2.8 years. There was no difference in OS between TT IIIB and TT IIIA. The total therapy (TT) IIIB phase 2 study incorporated bortezomib into tandem melphalan-based hematopoietic stem cell transplantation with dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide for induction/consolidation and bortezomib, lenalidomide, and dexamethasone (VRD) for maintenance in patients with newly diagnosed multiple myeloma (MM). This updated analysis presents a 15.4-year median follow-up. Of 177 patients, 21% patients had gene expression profile (GEP)-defined high-risk MM. 15-year progression free survival (PFS) was 27.9%. Median PFS was better in GEP-defined low-risk patients at 7.8 years and in International Staging System stage 1 patients at 8.7 years. Overall, median OS was 9.1 years, and 15-year overall survival (OS) was 35.9%. GEP-defined low-risk patients' median OS was 11.2 years, and that of GEP-defined high-risk patients was 2.8 years. There was no difference in OS between TT IIIB and TT IIIA. This study includes the longest follow-up of patients treated with maintenance VRD reported to date. In patients with GEP-defined low-risk, nearly half and one-third of patients without ongoing treatment showed no signs of progression at 10 and 15 years, respectively. One-third of patients survived more than 15 years, but 3 years of VRD maintenance did not improve outcomes for patients with GEP-defined high-risk MM. The study was registered on www.clinicaltrials.gov as #NCT00572169. |