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A425 EGFR Based on Cystatin-C, Creatinine, and Age Is Independently Associated with Survival in Myeloma
Clinical Studies Including Transplantation A425 EGFR Based on Cystatin-C, Creatinine, and Age Is Independently Associated with Survival in Myeloma MA Dimopoulos, E Kastritis, E Katodritou, E Tsiftsakis, D Christoulas, E Verrou, E Michalis, A Pouli, K Zervas, E Terpos Greek Myeloma Study Group
Introduction and Aims: Renal impairment (RI) is a common complication of multiple myeloma (MM). Cystatin-C (Cys-C) is considered as a sensitive marker of glomerular filtration rate (GFR). A recent study in > 3400 patients with chronic kidney disease showed that estimating GFR (eGFR) based on serum creatinine, Cys-C, age, gender and race (eGFR/Cys/Cr) provides the most accurate GFR estimates: eGFR = 177.6×Scr-0.65×CysC-0.57 × age-0.20 × (0.82 if female) × (1.11 if black). The aim of this study was to evaluate eGFR/Cys/Cr, compare it with eGFR assessed by MDRD equation and explore possible correlations with clinical data, including survival. Patients and Methods: We studied 157 newly-diagnosed MM patients (87 male/70 female; median age, 68 years) before any kind of therapy and evaluated both eGFR/Cys/ Cr and eGFR/MDRD. Serum Cys-C was determined by particle enhanced immunonephelometry (Dade Behring, Liederbach, Germany). Results: Serum Cys-C was increased in MM patients compared to 52 controls [median: 1.01 mg/L vs. 0.72 mg/L; P < .0001], and correlated with ISS (P < 0.001), bone disease status (P < .01), beta2-microglobulin (r = 0.648; P < .0001), creatinine (r = 0.705; P < .0001), and urea (r = 0.471; P < .0001). Median values of eGFR/Cys/Cr (68.7 mL/min/1.73 m2) were not different compared with those of eGFR/MDR (66.1 mL/min/1.73 m2). Furthermore, there was no difference in terms of number of patients with RI of different stages between the two estimates (ie, 8 patients had stage 5 RI with both estimates, while stage 4 RI had 13 patients based on eGFR/Cys/Cr and 12 based on eGFR/MDRD, and stage 3 RI had 43 with eGFR/Cys/Cr and 41 with eGFR/MDRD). The median survival was 48 months (median follow-up, 20 months). In univariate analysis eGFR/Cys/Cr (but not eGFR/MDRD), Cys-C, LDH, ISS, bone disease and myeloma subtype (light chain only MM vs. others) predicted for survival. In multivariate analysis only eGFR/Cys/Cr (= 0.004), bone disease (P = .018) and LDH (P = .01) had independent prognostic value with eGFR/Cys/Cr having the higher prognostic significance. Conclusion: eGFR/Cys/Cr estimates RI comparable to eGFR/MDRD. However, only eGFR/Cys/Cr strongly correlates with survival. This may be due to the better reflection of both renal function and tumor burden by eGFR/Cys/Cr as Cys-C is also overproduced by myeloma cells.
A426 Bortezomib or Lenalidomide to Treat Disease Relapse After Allogeneic Transplantation in Myeloma V Montefusco,1 AP Falcone,1 AM Carella,1 A Olivieri,2 G Sanpaolo,1 L Farina,3 F Spina,3 A Dodero,3 M Morelli,3 R Milani,3 N Cascavilla,1 P Corradini3
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Department of Hematology, IRCCS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy; 2Department of Oncology and Haematology, San Carlo Hospital, Potenza, Italy; 3Department of Haematology, Istituto Nazionale dei Tumori, Milano, Italy
Allogeneic stem cell transplantation (allo-HSCT) represents an effective treatment option for multiple myeloma (MM). However, clinical relapse or progression after allo-HSCT is rather common and new therapeutic strategies for salvage are needed. New drugs, in particular bortezomib and lenalidomide, are appealing for several reasons: (1) they have a very limited hematopoietic toxicity; (2) the mechanisms of antitumor activity are different from that of chemotherapy; (3) their activity encompasses also the modulation of immune response, with potential effects on the graft versus-myeloma effect. In order to evaluate the role of bortezomib and lenalidomide, we collected the data from 20 patients relapsing after allo-HSCT at 3 Italian institutions. Median age at transplantation was 53 years (range, 35-64 years). Donors were HLA-identical siblings in 15 and matched unrelated donors in 5 patients. After allo-HSCT, 9 patients developed acute graft-versus-host disease (GVHD), and 12 chronic GVHD (9 limited, 3 extensive). Nine patients were treated with bortezomib, 7 patients with lenalidomide, and 4 patients received bortezomib and, subsequently, lenalidomide. The median interval between allo-HSCT and bortezomib or lenalinomide treatments were 29 (range, 7-144), and 26 months (range, 7-66 months) respectively. The 13 patients treated with bortezomib received a median number of 3 courses (range, 1-7), in all cases with dexamethasone and, in 8 cases, also with thalidomide. Disease response was as follows: 5 CRs or nCRs, 4 VGPRs, 2 PRs, and 2 no response. The median duration of response (DOR) was 10 months (range, 6-43 months). Longer DOR were observed in patients receiving also thalidomide. The 11 patients treated with lenalidomide received a median number of 6 courses (range, 212), in all cases with dexamethasone. Disease response was as follows: 2 CRs, 2 VGPRs, 3 PRs, and 4 no response. The median DOR was 6 months (range, 4-12 months). Main toxicities were neuropathy for bortezomib, and neutropenia for lenalidomide. No grade IV toxicities were recorded. In one case only a GVHD worsening was observed. In conclusion, bortezomib and lenalidomide are effective therapeutic options for myeloma relapse after allo-HSCT. In addition, they can used safely before donor lymphocyte infusions.
A432 Long-Term Treatment with Lenalidomide in Previously Treated Subjects with Multiple Myeloma AA Amor, B Aguado, C Camara, A Velasco, F Garcia-Escribano Hematology Department, Hospital Universitario de la Princesa, Madrid
Introduction: Thalidomide or the proteasome inhibitor bortezomib improved the treatment outcomes in multiple myeloma, but the side effects of fatigue, neuropathy, constipation, and thrombotic events remain a concern. In nearly all patients who receive these drugs or other chemotherapy, the disease eventually relapses and is subsequently resistant to treatment. The published clinical trials of lenalidomide with dexamethasone in patients with treatment refractory or relapse multiple myeloma showed an increased efficacy and a tolerable safety
Clinical Lymphoma & Myeloma Supplement February 2009
Introduction and Aims: Renal impairment (RI) is a common complication of multiple myeloma (MM). Cystatin-C (Cys-C) is considered as a sensitive marker of glomerular filtration rate (GFR). A recent study in > 3400 patients with chronic kidney disease showed that estimating GFR (eGFR) based on serum creatinine, Cys-C, age, gender and race (eGFR/Cys/Cr) provides the most accurate GFR estimates: eGFR = 177.6×Scr-0.65×CysC-0.57 × age-0.20 × (0.82 if female) × (1.11 if black). The aim of this study was to evaluate eGFR/Cys/Cr, compare it with eGFR assessed by MDRD equation and explore possible correlations with clinical data, including survival. Patients and Methods: We studied 157 newly-diagnosed MM patients (87 male/70 female; median age, 68 years) before any kind of therapy and evaluated both eGFR/Cys/ Cr and eGFR/MDRD. Serum Cys-C was determined by particle enhanced immunonephelometry (Dade Behring, Liederbach, Germany). Results: Serum Cys-C was increased in MM patients compared to 52 controls [median: 1.01 mg/L vs. 0.72 mg/L; P < .0001], and correlated with ISS (P < 0.001), bone disease status (P < .01), beta2-microglobulin (r = 0.648; P < .0001), creatinine (r = 0.705; P < .0001), and urea (r = 0.471; P < .0001). Median values of eGFR/Cys/Cr (68.7 mL/min/1.73 m2) were not different compared with those of eGFR/MDR (66.1 mL/min/1.73 m2). Furthermore, there was no difference in terms of number of patients with RI of different stages between the two estimates (ie, 8 patients had stage 5 RI with both estimates, while stage 4 RI had 13 patients based on eGFR/Cys/Cr and 12 based on eGFR/MDRD, and stage 3 RI had 43 with eGFR/Cys/Cr and 41 with eGFR/MDRD). The median survival was 48 months (median follow-up, 20 months). In univariate analysis eGFR/Cys/Cr (but not eGFR/MDRD), Cys-C, LDH, ISS, bone disease and myeloma subtype (light chain only MM vs. others) predicted for survival. In multivariate analysis only eGFR/Cys/Cr (= 0.004), bone disease (P = .018) and LDH (P = .01) had independent prognostic value with eGFR/Cys/Cr having the higher prognostic significance. Conclusion: eGFR/Cys/Cr estimates RI comparable to eGFR/MDRD. However, only eGFR/Cys/Cr strongly correlates with survival. This may be due to the better reflection of both renal function and tumor burden by eGFR/Cys/Cr as Cys-C is also overproduced by myeloma cells.
A426 Bortezomib or Lenalidomide to Treat Disease Relapse After Allogeneic Transplantation in Myeloma V Montefusco,1 AP Falcone,1 AM Carella,1 A Olivieri,2 G Sanpaolo,1 L Farina,3 F Spina,3 A Dodero,3 M Morelli,3 R Milani,3 N Cascavilla,1 P Corradini3
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1
Department of Hematology, IRCCS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy; 2Department of Oncology and Haematology, San Carlo Hospital, Potenza, Italy; 3Department of Haematology, Istituto Nazionale dei Tumori, Milano, Italy
Allogeneic stem cell transplantation (allo-HSCT) represents an effective treatment option for multiple myeloma (MM). However, clinical relapse or progression after allo-HSCT is rather common and new therapeutic strategies for salvage are needed. New drugs, in particular bortezomib and lenalidomide, are appealing for several reasons: (1) they have a very limited hematopoietic toxicity; (2) the mechanisms of antitumor activity are different from that of chemotherapy; (3) their activity encompasses also the modulation of immune response, with potential effects on the graft versus-myeloma effect. In order to evaluate the role of bortezomib and lenalidomide, we collected the data from 20 patients relapsing after allo-HSCT at 3 Italian institutions. Median age at transplantation was 53 years (range, 35-64 years). Donors were HLA-identical siblings in 15 and matched unrelated donors in 5 patients. After allo-HSCT, 9 patients developed acute graft-versus-host disease (GVHD), and 12 chronic GVHD (9 limited, 3 extensive). Nine patients were treated with bortezomib, 7 patients with lenalidomide, and 4 patients received bortezomib and, subsequently, lenalidomide. The median interval between allo-HSCT and bortezomib or lenalinomide treatments were 29 (range, 7-144), and 26 months (range, 7-66 months) respectively. The 13 patients treated with bortezomib received a median number of 3 courses (range, 1-7), in all cases with dexamethasone and, in 8 cases, also with thalidomide. Disease response was as follows: 5 CRs or nCRs, 4 VGPRs, 2 PRs, and 2 no response. The median duration of response (DOR) was 10 months (range, 6-43 months). Longer DOR were observed in patients receiving also thalidomide. The 11 patients treated with lenalidomide received a median number of 6 courses (range, 212), in all cases with dexamethasone. Disease response was as follows: 2 CRs, 2 VGPRs, 3 PRs, and 4 no response. The median DOR was 6 months (range, 4-12 months). Main toxicities were neuropathy for bortezomib, and neutropenia for lenalidomide. No grade IV toxicities were recorded. In one case only a GVHD worsening was observed. In conclusion, bortezomib and lenalidomide are effective therapeutic options for myeloma relapse after allo-HSCT. In addition, they can used safely before donor lymphocyte infusions.
A432 Long-Term Treatment with Lenalidomide in Previously Treated Subjects with Multiple Myeloma AA Amor, B Aguado, C Camara, A Velasco, F Garcia-Escribano Hematology Department, Hospital Universitario de la Princesa, Madrid
Introduction: Thalidomide or the proteasome inhibitor bortezomib improved the treatment outcomes in multiple myeloma, but the side effects of fatigue, neuropathy, constipation, and thrombotic events remain a concern. In nearly all patients who receive these drugs or other chemotherapy, the disease eventually relapses and is subsequently resistant to treatment. The published clinical trials of lenalidomide with dexamethasone in patients with treatment refractory or relapse multiple myeloma showed an increased efficacy and a tolerable safety
Clinical Lymphoma & Myeloma Supplement February 2009