Assessment of vulnerability measures and their effect on survival in a real-life population of multiple myeloma patients registered at Marche Region Multiple Myeloma Registry.

UNLABELLED: Multiple myeloma (MM) therapy should be tailored according to patient characteristics although we do not know which ones to use. By studying the characteristics of 266 real-life patients, we found performance status (PS) and Charlson Comorbidity Index (CCI) as factors affecting survival of MM patients regardless of their disease characteristics. This study might help to select patients for tailoring therapy in clinical practice. BACKGROUND: Multiple myeloma is a typical disease of the elderly but how many and which patients can be considered 'vulnerable' and how this may affect patient outcome remain unsolved issues. PATIENTS AND METHODS: Data from 266 symptomatic MM patients registered at Marche MM registry from 2007 to 2010 were evaluated retrospectively. Vulnerability was defined as age > 75 years, PS (World Health Organization) ≥ 2, renal insufficiency (RI), bone fracture, cytopenias, and CCI score ≥ 1. Kaplan-Meier method and Cox regression were used to assess survival and associated factors. A vulnerability score (VS) incorporating significant vulnerability features was pursued to predict survival. RESULTS: Thirty-eight percent of patients were older than 75 years, 39% had PS = 2-4, 35% had at least 2 cytopenias, 40% had bone fracture, 14% RI, and 51% had CCI score ≥ 1. Cox regression selected international staging system (ISS) = III (hazard ratio [HR] = 1.6; P = .033), PS = 2-4 (HR = 2.5; P = .007), and CCI = 1-3 (HR = 2.1; P = .028) as factors associated with a worse overall survival. A VS including PS and CCI predicted median survival of 27 months in the 63 patients having a VS = 2 (both PS = 2-4 and CCI = 1-3) versus not reached (NR) in the 203 patients with VS = 0-1 (HR = 4.0; P < .0001). In younger patients multivariate analysis selected ISS = III (HR = 5.2; P = .006) and VS = 2 (HR = 5.5; P = .024) as factors associated with shorter survival whereas only VS = 2 (HR = 3.5; P = .002) affected worse survival in elderly. CONCLUSION: Such VS proved to be a powerful prognostic factor for survival of MM patients and it might be useful to identify true vulnerable patients regardless of age.

Thalidomide, dexamethasone, Doxil and Velcade (ThaDD-V) followed by consolidation/maintenance therapy in patients with relapsed-refractory multiple myeloma.

In newly diagnosed multiple myeloma (MM), three/four-drug combinations as induction therapy seem to be more effective compared with two-drug associations in terms of response rate and duration of remission. Moreover, there is an emergent body of evidences that consolidation/maintenance therapy improves the quality of response and remission duration. However, the impact of these strategies in relapsed/refractory MM (r-rMM) is still unknown. This phase II study explored the four-drug combination of thalidomide, dexamethasone, pegylated liposomal doxorubicin (pLD), and bortezomib (ThaDD-V) as induction followed by consolidation therapy based on bortezomib-dexamethasone and thalidomide-dexamethasone and maintenance therapy with thalidomide in r-rMM patients. The primary end points of this study were best response and toxicity of the planned therapy. Forty-six patients were enrolled. At the end of therapy, the best response was as follows: 37% complete response (CR), 34.5% VGPR, and 4.5% PR with an ORR of 76%. Patients receiving ≤ 2 prior regimens had a CR rate significantly higher than those heavily treated (41% vs 0%; p=0.010). With a median follow-up of 31 months, median time to progression (TTP) and OS were 18.5 months and 40 months, respectively. By a 6-month landmark analysis, patients who completed the protocol had a significantly longer TTP compared with those who did not because of toxicity (not reached vs 7 months; p<0.0001). After the dose intensity of bortezomib was reduced due to an excess of peripheral neuropathy (PN), grade 3 PN occurred in 7.5% of patients. ThaDD-V followed by consolidation-maintenance therapy seems to be very effective in patients with r-rMM provided that this procedure is used early on relapse when very deep responses seem to be the rule.

Infectious complications in patients with multiple myeloma treated with new drug combinations containing thalidomide.

The literature provides scant data concerning infectious complications and their effect on the outcome of patients with multiple myeloma (MM) treated with new drug combinations. Despite no substantial myelotoxic effect, thalidomide increases the risk of severe infections in patients with MM. We studied 202 patients who received regimens containing thalidomide in order to assess the time, type, outcome, and factors affecting development of severe infections, role of antibiotic prophylaxis, and effect of severe infections on final outcome. Thirty-eight patients (19%) developed a severe infection early during induction therapy and most infections were pneumonia. Only one patient died due to septic shock during neutropenia. No significant differences were reported in terms of progression-free survival (PFS) and overall survival (OS) between patients developing a severe infection and those who did not. Multivariate analysis determined a monoclonal component >3 g/dL and platelets <130 ,000/µL as factors associated with increased risk of severe infection. Primary antibiotic prophylaxis significantly decreased the probability of severe infection only in patients having both the above risk factors. Patients with MM receiving thalidomide combinations with high tumor burden are at high risk of developing severe infections and require primary antibiotic prophylaxis, whereas in other patients it is questionable. However, patient final outcome was not affected by infection development.

Melphalan, prednisone, and thalidomide versus thalidomide, dexamethasone, and pegylated liposomal doxorubicin regimen in very elderly patients with multiple myeloma: a case-match study.

The outcome of patients with multiple myeloma (MM) aged over 75 years remains poor, and the best therapeutic approach has still to be defined. We compared the response, toxicity, and outcome of 34 very elderly patients with MM receiving thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) to those of 34 patients matched for age, International Staging System (ISS), and creatinine who received melphalan, prednisone, thalidomide (MPT). ThaDD resulted in a significantly higher response: > or =PR (87.5% vs. 61.5%, p = 0.009) and > or =VGPR (55.5% vs. 29.5%; p = 0.03). No statistical differences were detected in terms of median probability of progression-free survival (PFS) and overall survival (OS) between the two treatments. Patients treated with MPT had more neutropenia, neuropathy, and heart toxicity, whereas thromboembolism resulted more frequently in patients receiving ThaDD. Therapy discontinuation occurred in 9% and 14.5% of patients treated with ThaDD and MPT, respectively. ThaDD can be considered a therapeutic option in very elderly patients with MM since it induces a faster and deeper response than that obtained with MPT, having similar safety profile.