Early mortality in myeloma patients treated with first-generation novel agents thalidomide, lenalidomide, bortezomib at diagnosis: A pooled analysis.

INTRODUCTION: Early toxic death (≤60 days of diagnosis) in elderly multiple myeloma (MM) patients is attributable to active disease, age and co-morbidities. Rate of early toxic deaths is 10% with conventional chemotherapy mainly due to infection and renal failure. Novel agents have improved MM outcome at the expense of newer toxicity. METHODS: We analyzed 1146 individual patient data to assess toxic deaths during induction treatment with first-generation novel agents thalidomide, lenalidomide, bortezomib. RESULTS: During first-line therapy, 119/1146 patients (10%) died for any cause, and 47/1146 (4%) due to toxicity, including 12/1146 (1%) early deaths. The 24-month cumulative incidence was 4.1% without any difference between bortezomib (18/503 patients, 4%) and lenalidomide (29/643patients, 5%; p = 0.31). Toxic deaths occurred in 34/1039 (3%) patients <80 years and 13/107 (12%) patients ≥80 years. Causes were cardiac events (28%), infections (26%) and vascular complications (15%). In a multivariate analysis, older age and unfavorable ISS stage increased the risk of death. CONCLUSION: First-generation novel agents significantly reduced toxic deaths compared to conventional chemotherapy. One third of deaths during first-line therapy were due to cumulative drug-related toxicities, thus supportive approaches and prevention strategies should be optimized. The higher mortality rate for toxicity in octogenarians confirms the need for a careful frailty assessment.

MET dysregulation is a hallmark of aggressive disease in multiple myeloma patients.

Abnormal activation of MET/HGF (Hepatocyte Growth Factor) pathway has been described in several tumours and increased HGF plasmatic levels have been detected in patients with aggressive multiple myeloma (MM). MET and HGF mRNA expression was investigated in 105 samples of purified plasma cells derived from newly diagnosed MM patients treated with bortezomib-based induction therapy. Gene expression was compared with response to therapy and clinical outcome. MET gene copy number was also evaluated. MET mRNA expression was higher in CD138(+) than in CD138(-) cells (median 76·90 vs. 11·24; P = 0·0009). Low MET mRNA expression characterized patients with better response (complete response or very good partial response) compared to other patients (median 56·10 vs. 134·83; P = 0·0006). After a median follow-up of 50 months, patients with high MET mRNA expression displayed a worse progression-free survival (PFS; P = 0·0029) and overall survival (OS; P = 0·0023) compared to those with low MET mRNA levels. Patients with both high MET mRNA expression and high ß2-microglobulin level (>5·5 mg/l) had further worse median PFS (P < 0·0001) and OS (P < 0·0001). Patients carrying 4 MET gene copies (8 out of 82, 9·8%) also had a short PFS. High MET mRNA expression identifies patients with dismal PFS and OS and the combination with high ß2-microglobulin further characterizes patients with worse outcome.

Extramedullary intracranial localization of multiple myeloma and treatment with novel agents: a retrospective survey of 50 patients.

BACKGROUND: Intracranial involvement in multiple myeloma is extremely rare. The effect of new drugs (eg, thalidomide, bortezomib, lenalidomide) with respect to old drugs (eg, alkylators, steroids) has not been reported. METHODS: We collected clinical and biological data of patients presenting with an osteo-dural or primary dural multiple myeloma (OD-DMM) or a central nervous system myelomatosis (CNS-MM) by sending a questionnaire to the centers of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA). RESULTS: A total of 50 patients were registered. New therapies were used in 35 patients, whereas 15 patients received old treatments. Twenty-five out of 50 patients obtained a complete remission or a very good partial remission (CR+VGPR). Overall survival (OS) for CNS-MM was 6 months, for OD-DMM 25 months. OS was 25 months for patients treated with new agents versus 8 months with old agents. Improved OS and progression-free survival were predicted by response (CR+VGPR) and by patients who underwent stem cell transplantation versus chemotherapy. ß2-Microglobulin >5 mmol/L was a poor prognostic factor. Multivariate analysis showed poor survival for patients with ß2-microglobulin >5 mmol/L and better survival for patients achieving CR+VGPR. CONCLUSIONS: The overall data highlight the relevance of therapy with new drugs in intracranial myeloma, providing a framework for future clinical trials.

Immediate occlusal loading of single lower molars using Brånemark System Wide-Platform TiUnite implants: an interim report of a prospective open-ended clinical multicenter study.

BACKGROUND: First and second molars in the lower jaw are the most commonly missing teeth. As in other jaw regions with tooth loss, implant therapy is an attractive concept. Owing to the wide dimension of the molar teeth, wide implants seem to be a natural choice. However, wide implants in posterior mandibular regions sometimes present a problem. As an oxidized surface seems to facilitate implant integration and to result in a stronger fixation to bone, it was hypothesized that this surface would improve the performance of wide implants in posterior mandibles. As high initial stability most often is achieved in this region, it was hypothesized that the load per se is not a problem. PURPOSE: The purpose of the present study is to evaluate immediate loading of Brånemark System TiUnite Wide-Platform implants (Nobel Biocare AB, Gothenburg, Sweden) supporting single molar crowns in the lower jaw. MATERIALS AND METHODS: The study includes 44 patients treated in three separate private dental offices between March 2001 and June 2002. A total of 50 implants were placed, and all implants have passed the 6-month follow-up; 24 have been followed up for 1 year. All implants were provided with provisional crowns in centric occlusion at the time of surgery. RESULTS: No implant has been lost. Marginal bone levels were found in accordance with normal biologic width requirements. Resonance frequency analysis showed high and consistent implant stability. No biomechanical problems were found associated with the use of wide implants, and the potential physiologic problem in dense mandibular bone was eliminated. CONCLUSION: Although limited by being a short-term study, the result encourages immediate loading of single Brånemark System TiUnite Wide-Platform implants placed in the molar regions in the lower jaw.