Effect of induction therapy with lenalidomide, doxorubicin and dexamethasone on bone remodeling and angiogenesis in newly diagnosed multiple myeloma

被引:11
作者
Terpos, Evangelos [1 ]
Katodritou, Eirini [2 ]
Symeonidis, Argiris [3 ]
Zagouri, Flora [1 ]
Gerofotis, Antonis [2 ]
Christopoulou, Georgia [3 ]
Gavriatopoulou, Maria [1 ]
Christoulas, Dimitrios [4 ]
Ntanasis-Stathopoulos, Ioannis [1 ]
Kourakli, Alexandra [3 ]
Konstantinidou, Pavlina [2 ]
Kastritis, Efstathios [1 ]
Dimopoulos, Meletios A. [1 ]
机构
[1] Univ Athens, Sch Med, Dept Clin Therapeut, Athens, Greece
[2] Theagenio Canc Hosp, Dept Hematol, Thessaloniki, Greece
[3] Univ Patras, Div Hematol, Dept Internal Med, Med Sch, Patras, Greece
[4] 251 Gen Air Force Hosp, Dept Hematol, Athens, Greece
关键词
multiple myeloma; frontline therapy; lenalidomide; bone markers; angiogenesis; STEM-CELL TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; PLUS DEXAMETHASONE; OSTEOGENIC DIFFERENTIATION; LIPOSOMAL DOXORUBICIN; OSTEOCLAST FORMATION; BORTEZOMIB; THALIDOMIDE; COMBINATION; VINCRISTINE;
D O I
10.1002/ijc.32125
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
There is limited data regarding the efficacy and safety of lenalidomide, adriamycin and dexamethasone (RAD) combination on newly diagnosed multiple myeloma (NDMM) patients. There is also scarce information about the effect of lenalidomide on bone metabolism and angiogenesis in NDMM. Thus, we conducted a Phase 2 study to evaluate the efficacy and safety of RAD regimen as induction in transplant-eligible NDMM patients and we studied the effects on bone metabolism and angiogenesis. A total of 45 patients were enrolled. Following four cycles of RAD, the overall response rate was 66.7% and after a median follow up of 29.1 months (range 21.0-34.9), the median survival outcomes have not been reached yet. RAD had a favorable toxicity profile and did not impair stem cell collection. RAD significantly reduced bone resorption markers CTX (p = 0.03) and TRACP-5b (p < 0.01). Interestingly, RAD also increased bone formation markers bone-specific alkaline phosphatase (p = 0.036), procollagen type 1 amino-terminal propeptide (p = 0.028) and osteocalcin (p = 0.026), which has not been described before with lenalidomide-containing regimens in the absence of bortezomib coadministration. Furthermore, the angiogenic cytokines VEGF (p = 0.01), angiogenin (p = 0.02) and bFGF (p < 0.01) were significantly reduced post-RAD induction. Our results suggest that RAD is an effective induction regimen before autologous stem cell transplantation with beneficial effects on bone metabolism and angiogenesis.
引用
收藏
页码:559 / 568
页数:10
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