Myeloma in scar tissue--an underreported phenomenon or an emerging entity in the novel agents' era? A single center series.

Tumor relapse in scar tissue is uncommon in cancer patients. Likewise, extramedullary plasmacytoma (EMP) relapse in scar tissue in the setting of multiple myeloma (MM) has been rarely reported. We report a series of 3 patients whose disease progressed as EMP at the site of a wound from previous invasive procedures. All 3 patients were treated for the relapsed disease with different treatment modalities, but failed to respond adequately and died several months after relapse. At original MM diagnosis, all had advanced-stage disease. They were treated with novel agents with or without autologous hematopoietic stem cell transplantation and achieved either a complete or very good partial response. We suggest that these treatments, which have become the standard of care in MM, may permit a predominance of myeloma subclones which are independent of the bone marrow microenvironment. These myeloma subclones then gain a survival advantage in the active scar-tissue niche, allowing for their uncontrolled proliferation. This case series might represent an underreported phenomenon and therefore may indicate an emerging and difficult-to-treat disease in the era of targeted therapies in MM. Physicians treating MM should be aware of this phenomenon, especially when referring their patients for invasive procedures.

Toxicity of autologous hematopoietic cell transplantation in patients with multiple myeloma - comparison between two different induction regimens.

BACKGROUND: Induction therapy in patients with multiple myeloma has evolved from chemotherapy-based to novel agents-based regimens. We compared autologous hematopoietic cell transplantation (HCT)-associated toxicity in patients induced with VTD-PACE (bortezomib, thalidomide, dexamethasone, cisplatinum, adriamycin, cyclophosphamide, and etoposide) to that of patients induced with novel agents-only therapy. METHODS: We reviewed medical charts of all patients with multiple myeloma who were given induction therapy and HCT. RESULTS: Between the years 2007 and 2011, 38 patients received VTD-PACE, and 31 patients received novel agents-only regimen. Mean time to neutrophil and platelets recovery was longer in patients given VTD-PACE compared with those given novel agents-only regimen (7 vs. 6 d, p = 0.0002 and 11 vs. 10 d, p = 0.04, respectively). We observed higher rates of grade 2-4 mucositis and parenteral narcotic analgesia administration in the patients given VTD-PACE (45% vs. 19%, p = 0.05 and 37% vs. 12%, p = 0.07, respectively). Progression free survival and overall survival were not statistically significantly different between the two groups. CONCLUSIONS: A more intensive induction regimen was associated with slightly delayed counts recovery and a higher rate of mucositis during HCT compared with novel agents-only regimens. A longer follow-up is needed to assess long-term disease control of the two different regimens.

Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. melphalan-prednisone in the phase III VISTA trial in multiple myeloma.

OBJECTIVES: Bone disease is a key presenting feature of myeloma. This post hoc analysis of the phase III VISTA trial of bortezomib plus melphalan-prednisone (VMP) vs. MP in previously untreated myeloma patients assessed clinical bone disease events and changes in alkaline phosphatase (ALP), a marker for osteoblast activation, and serum Dickkopf-1 (DKK-1), an inhibitor of osteoblast differentiation, during treatment. METHODS: Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m(2) , days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, days 1, 8, 22, 29, cycles 5-9, plus melphalan 9mg/m(2) and prednisone 60mg/m(2) , days 1-4, cycles 1-9; N=344) or MP alone (N=338). RESULTS: Rates of bisphosphonates use during treatment (73% vs. 82%), progression because of worsening bone disease (3% vs. 11%), and requirement for subsequent radiotherapy (3% vs. 8%) were lower with VMP vs. MP. Median maximum ALP increase was significantly higher with VMP vs. MP overall (49.7% vs. 30.3%, P=0.029), and higher by response group (complete response [CR]: 68.7% vs. 43.9%; partial response [PR]: 41.5% vs. 31.2%). Greater maximum ALP increase was strongly associated with achievement of CR (P≤0.0001) and CR/PR (P≤0.01). Median DKK-1 decreased with VMP by 694.4pg/mL and increased with MP by 1273.3pg/mL from baseline to day 4 (P=0.0069). Available radiologic data revealed evidence of bone healing in 6/11 VMP-treated patients, who achieved best responses of three CR, one PR, and two stable disease. CONCLUSIONS: These results suggest a positive effect of bortezomib on bone metabolism and potentially bone healing in myeloma.

Multiple myeloma treatment strategies with novel agents in 2011: a European perspective.

The arrival of the novel agents thalidomide, bortezomib, and lenalidomide has significantly changed our approach to the management of multiple myeloma and, importantly, patient outcomes have improved. These agents have been investigated intensively in different treatment settings, providing us with data to make evidence-based decisions regarding the optimal management of patients. This review is an update to a previous summary of European treatment practices that examines new data that have been published or presented at congresses up to the end of 2010 and assesses their impact on treatment practices.

Total therapy-based treatment for multiple myeloma--a single center experience.

Incorporation of novel biological agents has become the cornerstone of treatment in multiple myeloma. For the last 4 years we have adopted the more intensified approach, previously published as total therapy 3 by the Arkansas group and used it with local modifications. This study aims to evaluate the efficacy and safety of the Arkansas protocol-based treatment outside clinical trial in a tertiary medical center in Israel. We retrospectively analyzed 23 patients. Seventy-three percent of the patients achieved very good partial remission (VGPR) before autologous stem cell transplantation (ASCT). Eighty-six percent of the patients achieved at least VGPR after tandem ASCT. Two-year overall survival was estimated as 70%. Four patients died during treatment, one as a result of disease progression. We conclude that this protocol is effective and rather safe. Further clinical trials should assess which subgroups of patients would benefit most from this approach.