Three years of maintenance with VRD in multiple myeloma: results of total therapy IIIB with a 15-year follow-up.

"Conflict-of-interest disclosure: The authors report no competing financial interests."

"This work was supported by National Cancer Institute grant CA 55813."

"Patients with newly diagnosed MM received 2 cycles of VTD-PACE (VTD and a 4-day continuous infusions of cisplatin, doxorubicin, cyclophosphamide, and etoposide) as induction before, and as consolidation therapy after, melphalan–based tandem HSCT, which was followed by 3 years of VRD with monthly cycles of bortezomib 1.0 mg/m2 (days 1, 4, 8, and 11) in year 1 followed by weekly administration in years 2 and 3. For all 3 years, lenalidomide was administered on days 1 to 20 (15 mg), then on days 21 to 28 (5 mg) of each 28-day cycle. Dexamethasone (20 mg) was administered on days 1 to 4 and 8 to 11 of 28-day cycle of year 1 and then weekly with bortezomib in years 2 and 3. Details on treatments administered and dose modifications were previously published. Gene expression profile (GEP) of CD138-purified plasma cells was conducted to determine the 70-gene-derived risk score, molecular subgroup designation, and delTP53 status., The molecular subgroup designations included CCND-1 without CD20 expression (CD-1) or with CD20 expression (CD-2), MAF/MAFB, MMSET/FGFR3, hyperdiploidy, low bone disease, myeloid, and proliferation., , All patients were followed regularly after completion of treatment. The study was registered on ClinicalTrials.gov under identifier NCT00572169. 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."