Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma: 5‐year follow‐up

Abstract

SummaryThis follow‐up extension of a randomised phase II study assessed differences in long‐term outcomes between bortezomib‐thalidomide‐dexamethasone (VTD) and VTD‐cyclophosphamide (VTDC) induction therapy in multiple myeloma. Newly diagnosed patients (n = 98) were randomised 1:1 to intravenous bortezomib (1·3 mg/m2; days 1, 4, 8, 11), thalidomide (100 mg; days 1–21), and dexamethasone (40 mg; days 1–4, 9–12), with/without cyclophosphamide (400 mg/m2; days 1, 8), for four 21‐day cycles before stem‐cell mobilisation/transplantation. After a median follow‐up of 64·8 months, median time‐to‐next therapy was 51·8 and 47·9 months with VTD and VTDC, respectively. Type of subsequent therapy was similar in both arms. After adjusting for asymmetric censoring, median time to progression was not significantly different between VTD and VTDC [35·7 vs. 34·5 months; Hazard ratio (HR) 1·26, 95% confidence interval: 0·76–2·09; P = 0·370]. Five‐year survival was 69·1% and 65·3% with VTD and VTDC, respectively. When analysed by minimal residual disease (MRD) status, overall survival was longer in MRD‐negative versus MRD‐positive patients with bone marrow‐confirmed complete response (HR 3·66, P = 0·0318). VTD induction followed by transplantation provides long‐term disease control and, consistent with the primary analysis, there is no additional benefit from adding cyclophosphamide. This study was registered at ClinicalTrials.gov (NCT00531453).

Induction regimens for transplant-eligible patients with newly diagnosed multiple myeloma: a network meta-analysis of randomized controlled trials

“…Our NMA finally included 14 RCTs (full texts available for 13 studies12,14,21,22,24–32 and one conference abstract33). Details of induction regimens of included RCTs are provided in Table 1.…”

“…In total, there were 14 induction regimens, by which 17 pairwise comparisons were established (Figure 2). Only two trials included multiple arm,26,32 and others included two arms 12,14,21–25,27–31,33. All 14 trials reported ORR outcome, but eight out of 14 trials reported OS and PFS outcome, respectively.…”

“…For some trials in which the HR and its 95% CI for OS and PFS were not reported but the relevant data for imputation were provided, Tierney et al’s method19 was used for calculation. Besides, we reconstructed IPD using Guyot et al’s20 method and performed survival analysis to make a comparison between TAD and VTD in terms of OS, based on extracted arm data from two independent trials 21,22. All the above-mentioned procedures were independently accomplished by two researchers (Z-HZ and J-FC).…”

Bortezomib, Thalidomide, and Dexamethasone (VTD) Induction Results in Better Overall Survival than Adriamycin, Thalidomide, and Dexamethasone (ATD) Induction in Previously Untreated Myeloma Patients Eligible for Transplants

“…Therefore, we extracted the arm data for these 2 regimens from 2 individual RCTs [3,4,5], and evaluated the OS based on reconstructed individual patient data as described previously [2]. Before survival analysis, baseline characteristics were compared, and early efficacy (response after induction) was analyzed (Table 1).…”

Proteasome inhibitors: situation and prospects (literature review and own data)

“…в 2 равные группы были вклю-чены 315 пациентов с рефрактерной ММ. В результате карфилзомиб по сравнению со стероидной терапией и циклофосфаном показал одинаковую 10-месячную ВБП и улучшенную на 7,5 % ОВ [9]. В исследовании III фазы (n = 792) на 2 равных когортах пациентов про-демонстрировано значительное увеличение ВБП в груп-пе KLD по сравнению с группой LD: 26,3 мес против 17,6 мес соответственно [10].…”