Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study

Abstract

The NCI Common Terminology Criteria for Adverse Events v3.0 is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.

Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial

“…In contrast, as reported in other recent studies, overlapping toxicities may significantly increase the rate of AEs, such as those seen with VDCR, but may also contribute to less than expected efficacy results of regimens, presumably due to treatment delays and discontinuations. 15,16,25 The results presented herein further validate the very high quality of responses seen with the RVD regimen. 6,15,16,26 Furthermore, our results suggest that the addition of a fourth drug, specifically PLD, may improve the depth and duration of response for all patients compared with RVD.…”

“…15,16,25 The results presented herein further validate the very high quality of responses seen with the RVD regimen. 6,15,16,26 Furthermore, our results suggest that the addition of a fourth drug, specifically PLD, may improve the depth and duration of response for all patients compared with RVD. Within the limitations of a historical comparison, it is notable that the RVDD regimen produced higher responses after 4 and 8 cycles compared with RVD (Table 5), 6 suggesting a potentially more rapid cytoreduction; however, ultimately, the rate of best responses was comparable between the 2 trials overall.…”

“…The flow of patients through this phase 1/2 trial is presented in Figure 1. Patients were treated with escalating doses of lenalidomide (15,20, and 25 mg/d) on days 1-14 of each 21-day cycle for a total of 4-8 cycles; bortezomib 1.3 mg/m 2 on days 1, 4, 8, and 11; PLD at escalating doses (20 and 30 mg/m 2 ) on day 4; and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 during cycles 1-4, reduced to 10 mg on the same schedule for cycles 5-8. 6 Patients who achieved Ն PR could stop treatment at any point after 4 cycles and proceed to stem cell (SC) mobilization as per institutional guidelines and autologous SC transplantation (ASCT).…”

“…14 Furthermore, the 4-drug regimen of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide (VDCR) has recently been shown to be highly active and generally well tolerated in patients with newly diagnosed MM, although some additional toxicity was noted. 15,16 We hypothesized that combining the 4 active drugs from the RVD and VDD regimens into one regimen, specifically RVDD (lenalidomide, bortezomib, PLD, and dexamethasone) might further increase CR/nCR and VGPR rates and thus potentially improve outcome. In preclinical studies, the RVDD combination demonstrated a 2-to 4-fold higher activity compared with 2-and 3-drug combinations of the component drugs, 17 with earlier studies demonstrating synergy between these agents.…”

The current status of minimal residual disease assessment in myeloma

“…However, with newer treatment approaches, we can achieve CR in a large majority of patients, including a significant proportion with stringent CR representing lack of clonal plasma cells in the marrow by immunophenotyping. [5][6][7] Despite this level of response, studies have shown that the vast majority of patients have residual tumor cells that can be detected with a variety of sensitive techniques. [8][9][10][11] Several studies have demonstrated a consistent improvement in progression-free survival (PFS) with attainment of CR, but its impact on overall survival (OS) has been varied.…”