Leukemia Research 34 (2010) 1395–1397 Contents lists available at ScienceDirect Leukemia Research journal homepage: www.elsevier.com/locate/leukres Brief communication Reversibility of renal failure in newly diagnosed patients with multiple myeloma and the role of novel agents Maria Roussou, Efstathios Kastritis, Dimitrios Christoulas, Magdalini Migkou, Maria Gavriatopoulou, Irini Grapsa, Erasmia Psimenou, Dimitra Gika, Evangelos Terpos, Meletios A. Dimopoulos ∗ Department of Clinical Therapeutics, University of Athens School of Medicine, 80 Vas. Sofias, Athens 11528, Greece article info Article history: Received 3 March 2010 Received in revised form 27 April 2010 Accepted 28 April 2010 Available online 26 May 2010 Keywords: Multiple myeloma Renal impairment Bortezomib Thalidomide Lenalidomide Conventional chemotherapy abstract The purpose of this analysis was to assess the effect of novel agent-based regimens on the improvement of renal impairment (RI) in newly diagnosed patients with multiple myeloma. Ninety-six consecutive patients with RI received conventional chemotherapy (CC)-based regimens (n = 32), IMiDs-based regi- mens (n = 47) or bortezomib-based regimens (n = 17) as frontline therapy. Improvement of RI was more frequent in patients treated with novel agents (79% in IMiD- and 94% in bortezomib-treated groups versus 59% in CC-treated group; p = 0.02). Bortezomib-based regimens and CrCl > 30 ml/min at baseline indepen- dently correlated with a higher probability of at least renal partial response (PRrenal) and with a shorter time to PRrenal or better. Thus bortezomib-based regimens may be the preferred treatment for newly diagnosed myeloma patients with RI. © 2010 Elsevier Ltd. All rights reserved. 1. Introduction Renal impairment (RI) is a common complication of multiple myeloma (MM). Depending on the definition of RI, this compli- cation is reported in 20–40% of MM patients. About one-fifth of myeloma patients have a serum creatinine higher than 2 mg/dl at the time of diagnosis. Most patients have moderate renal fail- ure with a serum creatinine lower than 4 mg/dl [1]. High-dose dexamethasone-based regimens have been extensively used for the initial management of MM patients presenting with RI [2]. Recently, novel agent-based regimens have been introduced in the frontline treatment of MM but their effect on the reversibil- ity of RI and the potential predictive factors has not yet been fully clarified. The purpose of our analysis was to assess the effect of novel agent-based regimens on RI improvement and compare their efficacy with that of conventional chemotherapy (CC) and dexam- ethasone. 2. Patients and methods Ninety-six consecutive, newly diagnosed, patients with MM and RI, who were treated over the last decade in our center, were evaluated. RI was defined as a sustained estimated creatinine clearance (CrCl) < 50 ml/min, calculated by the Cockroft–Gault formula, despite volume replacement and reversal of hypercal- ∗ Corresponding author. Tel.: +30 210 3381540; fax: +30 210 3381511. E-mail address: mdimop@med.uoa.gr (M.A. Dimopoulos). cemia. Patients were divided into three groups according to the type of frontline anti-myeloma treatment: group A included 32 patients who received CC plus dexamethasone (VAD, VAD-like regimens, melphalan plus dexamethasone), while group B included 47 patients who received IMiDs-based regimens (thalido- mide or lenalidomide with high-dose dexamethasone and/or cyclophoshamide or melphalan) and group C 17 patients who received bortezomib and dexamethasone- containing regimens. High-dose dexamethasone was given at the standard dosage in all regimens and no low-dose dexamethasone was used in the study population. Besides anti-myeloma treatment, all patients received supportive care which included rigorous intravenous hydration, alkalization of urine, correction of hyper- calcemia and discontinuation of all nephrotoxic agents. Renal dialysis was offered to all patients with an appropriate indication. The degree of improvement of renal function was evaluated according to the criteria proposed recently [3]. Renal complete response (CRrenal) was defined as sustained (i.e. lasting at least two months) improvement of CrCl from <50 ml/min at baseline to ≥60 ml/min. Renal partial response (PRrenal) was defined as sustained improvement of CrCl from <15 at baseline to 30–59 ml/min. Renal minor response (MRrenal) was defined as sustained improvement of baseline CrCl of <15 ml/min to 15–29 ml/min or if baseline CrCl was 15–29 ml/min improvement to 30–59 ml/min. Myeloma response was defined as ≥50% decrease of myeloma protein in the serum and ≥90% reduction of Bence Jones proteinuria. Differences among various groups were compared with the  2 -test for cat- egorical variables (using Fisher’s exact test when appropriate) and with the Mann–Whitney test or ANOVA for continuous variables. Logistic regression analysis was used for multivariate analysis by entering all significant variables (p < 0.05) that were associated with renal response. Time to renal response was calculated from the date of initiation of treatment until the date when criteria for renal response were first met. Patients, who died before renal response could be evaluated, were censored at the time of their death. Survival was calculated from the date of treat- ment initiation until the date of death or last follow-up and was plotted with the Kaplan–Meier method. Multivariate analysis was performed by entering all signif- icant variables that were associated with time to renal response in the univariate analysis into a Cox proportional Hazards model. 0145-2126/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2010.04.024