Roman Hájek

Consensus recommendations for risk stratification in multiple myeloma: Report of the International Myeloma Workshop Consensus Panel 2

A panel of members of the 2009 International Myeloma Workshop developed guidelines for risk stratification in multiple myeloma. The purpose of risk stratification is not to decide time of therapy but to prognosticate. There is general consensus that risk stratification is applicable to newly diagnosed patients; however, some genetic abnormalities characteristic of poor outcome at diagnosis may suggest poor outcome if only detected at the time of relapse. Thus, in good-risk patients, it is necessary to evaluate for high-risk features at relapse. Although detection of any cytogenetic abnormality is considered to suggest higher-risk disease, the specific abnormalities considered as poor risk are cytogenetically detected chromosomal 13 or 13q deletion, t(4;14) and del17p, and detection by fluorescence in situ hybridization of t(4;14), t(14;16), and del17p. Detection of 13q deletion by fluorescence in situ hybridization only, in absence of other abnormalities, is not considered a high-risk feature. High serum β(2)-microglobulin level and International Staging System stages II and III, incorporating high β(2)-microglobulin and low albumin, are considered to predict higher risk disease. There was a consensus that the high-risk features will change in the future, with introduction of other new agents or possibly new combinations.

Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project

The combination of serum β2-microglobulin and albumin levels has been shown to be highly prognostic in myeloma as the International Staging System (ISS). The aim of this study was to assess the independent contributions of ISS stage and cytogenetic abnormalities in predicting outcomes. A retrospective analysis of international studies looking at both ISS and cytogenetic abnormalities was performed in order to assess the potential role of combining ISS stage and cytogenetics to predict survival. This international effort used the International Myeloma Working Group database of 12u2009137 patients treated worldwide for myeloma at diagnosis, of whom 2309 had cytogenetic studies and 5387 had analyses by fluorescent in situ hybridization (iFISH). Comprehensive analyses used 2642 patients with sufficient iFISH data available. Using the comprehensive iFISH data, combining both t(4;14) and deletion (17p), along with ISS stage, significantly improved the prognostic assessment in terms of progression-free survival and overall survival. The additional impact of patient age and use of high-dose therapy was also demonstrated. In conclusion, the combination of iFISH data with ISS staging significantly improves risk assessment in myeloma.

The effect of pegylated liposomal doxorubicin plus bortezomib in multiple myeloma patients with renal insufficiency

8562 Background: Renal dysfunction (RD) is common in patients with multiple myeloma (MM) and has been associated with poor outcomes. Orlowski et al, 2007, demonstrated that pegylated liposomal doxorubicin (PLD) + bortezomib (B) for pts with relapsed/refractory MM who have received at least one prior therapy significantly increased median time to progression (TTP) (9.3 vs. 6.5 months, p = 0.00004) compared with B alone. We wished to determine the efficacy and feasibility of PLD + B in relapsed/refractory MM patients with renal insufficiency (RI) (creatinine clearance (CrCl) < 60 ml/min). Methods: Eligible pts who were randomized received bolus IV B 1.3 mg/m2 on days 1, 4, 8 and 11 of each 3-week cycle (n = 322) or the same B regimen plus IV PLD 30 mg/m2 on day 4 (n = 324) of each cycle. 193 pts with RI from this trial were analyzed retrospectively to determine the impact of RI on the efficacy and safety of PLD + B, as well as the effect on renal function. Pts with severe RI (CrCl ≤ 30 ml/min) were excluded...