Effects of single‐agent bortezomib as post‐transplant consolidation therapy on multiple myeloma‐related bone disease: a randomized phase II study

Abstract

Summary This phase II study explored the effects of bortezomib consolidation versus observation on myeloma‐related bone disease in patients who had a partial response or better after frontline high‐dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35‐day cycles of bortezomib 1·6 mg/m2 intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent‐to‐treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End‐of‐treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression‐free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival.

Bortezomib-based consolidation or maintenance therapy for multiple myeloma: a meta-analysis

“…The contradictory effects on OS shown in Mellqvist's study might be due to the fact that all patients were bortezomib-naive before consolidation and more patients in the control group received bortezomib-containing intensive therapy after first relapse (48/183 vs. 19/187) 25 . The study by Sezer et al 22 revealed similar effects on OS in the bortezomib arm compared with observation (HR = 1.01). Of note, none of these studies was statistically significant in terms of OS.…”

“…Of the ten included RCTs [19][20][21][22][23][24][25][26][27] , there were nine phase III studies and one phase II study included in the analysis. Bortezomib-based regimens were administered as consolidation therapy in seven RCTs [19][20][21][22]25,27 and as maintenance therapy in three RCTs 23,24,26 , following the initial therapy. Only one RCT was conducted in the non-transplantation setting 24 .…”

“…Consolidation therapy for MM is given as a short course of chemotherapy after the initial therapy, particularly in patients who have undergone ASCT. We identified seven RCTs (published in six articles) [19][20][21][22]25,27 comparing consolidation with bortezomib-based regimens vs. non-bortezomib-based regimens or no consolidation. Consolidation was given after ASCT in all seven trials.…”

Consolidation with carfilzomib, lenalidomide, and dexamethasone (KRd) following ASCT results in high rates of minimal residual disease negativity and improves bone metabolism, in the absence of bisphosphonates, among newly diagnosed patients with multiple myeloma

“…However, the evaluation of bone markers in the consolidation setting should be performed cautiously. The administration of bone-modifying agents during the induction treatment may have a residual beneficial effect, and thus, significant changes in bone markers may not become evident during the consolidation phase 15 . All our patients had received upfront bortezomib-based regimens with bisphosphonates; thus, several bone markers may have reached their plateau levels.…”

Consolidation therapy with the combination of bortezomib and lenalidomide (VR) without dexamethasone in multiple myeloma patients after transplant: Effects on survival and bone outcomes in the absence of bisphosphonates

“…Thus, the evaluation of consolidation regimens in terms of efficacy and bone‐related markers is intriguing. Regarding the latter, published data are rather scarce . Therefore, the aim of this prospective study was to assess the efficacy and safety of bortezomib and lenalidomide (VR) combination, without dexamethasone, as consolidation regimen in transplant‐eligible NDMM patients and also determine its effects on bone metabolism and SRE incidence in the absence of bisphosphonates (BPs) coadministration.…”