Abstract
Multiple myeloma (MM) remains an incurable disease, with significant variation in the response and survival even with current treatment modalities, such as high-dose chemotherapy (CTx) and autologous stem cell transplantation (auto-SCT), novel drugs and intensive supportives. Hence, prognostic parameters that help to predict the benefit of different therapeutics are of utmost importance to be defined further. The objective of this analysis was to determine whether treatment selection and response are markedly influenced by specific clinico-pathological parameters and how these effect overall survival (OS). Of 143 consecutive MM patients (pts) receiving either standard therapy (Std-CTx, group A, n=79) or auto-SCT (group B, n=64) at our center between 1997–2003, gender, age, MM-type, -stage, number of CTx lines, LDH,β 2-MG and bone marrow (BM) infiltration were evaluated on response and survival in uni- and multivariate analyses and hazard ratios (HR) were determined. To further pay tribute to pts’ average age, as MM is primarily a disease of the elderly, special attention was paid to the influence of the performance status (Karnofsky Index=KI) and number of concurrent diagnoses (CD). Pts in groups A and B were comparable in terms of gender distribution, MM type, CD and LDH-level. However, group A as compared to B pts were older (65 vs. 56 yrs), had received more radiation (26 vs. 19%) and showed higher β2-MG (5 vs. 2.3g/L; respectively). Moreover, pts in group B as compared to A had more advanced disease (Durie and Salmon [D&S] stage II/III: 92 vs. 65%), a higher BM-infiltration (40 vs. 30%), and were treated later in their disease course. In group A pts, HR were increased for β2-MG>3, D&S stage II/III, stage B disease, CD>1, LDH>200U/L and age >60y, and HR decreased for females and KI>80%, reaching significance for β2-MG, D&S stage II/III, stage B disease, CD and KI. Although these HR were also observed for group B pts, none of these prognostic factors reached statistical significance. Multivariate analysis on all pts identified β2-MG >3mg/L and age >60y as independent prognostic factors, with HRs of 3.6 (95% CI 1.6–8.1) and 2.1 (CI 0.9–5.0), respectively. Of note, current CR/PR rates for group A and B pts are 4 vs. 20%, and at last follow-up (6/2006) median OS from treatment initiation is 49.5% vs. 61.4%, respectively. Our data show that an elevated β2-MG, D&S stage II/III, stage B disease, more than 1 CD and reduced performance status before therapy, negatively influence response and OS in Std-group pts, whereas these do not significantly impact HR in auto-SCT pts. We conclude that MM pts benefit from auto-SCT independently of prognostic factors which, however, do impact outcome with Std-CTx alone. Since randomized trials have repetitively shown response and survival with auto-SCT to be superior to Std-CTx, we propose that pts with the above prognostic factors should be carefully evaluated for intensive therapies, as this analysis accentuates that auto-SCT is the treatment of choice for eligible MM pts.
Efficacy of growth hormone in improving the pregnancy rate in poor responders in ART
