The randomized pivotal phase III FIRST trial (Frontline Investigation of lenalidomide/dexamethasone [Rev/Dex] versus Standard Thalidomide; IFM 2007-01/ MM-020; clinicaltrials.gov identifier: 00689936; EudraCT No. 2007-004823-39) compared the efficacy and safety of Rd, administered continuously until progressive disease (PD) or for a fixed 18-month duration (Rd18), with MPT given for 18 months in NDMM patients who were aged 65 years or over, or who were aged under 65 years and ineligible for stem cell transplantation. Continuous Rd showed improved progression-free survival (PFS) and overall survival (OS) benefit at interim analysis compared with MPT. 19 Although extending survival is clearly the ultimate treatment ©2015 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2014 The online version of this article has a Supplementary Appendix. Manuscript received on November 14, 2014. Manuscript accepted on March 6, 2015 We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients' health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeatedmeasures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide.Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide [20][21][22][23] In this population, treatment objectives should be to improve disease management by delaying disease progression, optimizing re...
In 2003 the Fondazione Italiana Linfomi (FIL) started a clinical research program for investigating initial treatment of frail elderly patients with diffuse large B-cell lymphoma (DLBCL) identified by Comprehensive Geriatric Assessment (CGA). From 2003 to 2006, 334 elderly patients underwent CGA assessment, and 99 patients were classified as frail. Frail patients had a median age of 78 years, stage III-IV disease in 62% and age-adjusted International Prognostic Index (aaIPI) of 2-3 in 53%. Treatment consisted of several different regimens according to physician discretion. After a median follow-up of 36 months, 5-year overall survival (OS) was 28%. In multivariate analysis, aaIPI 2-3 (p = 0.005) and the presence of respiratory comorbidity (p = 0.044) were the only factors that showed independent correlation with OS. Frail patients had a poorer outcome compared with fit patients also if they were treated with rituximab-containing combination chemotherapy (hazard ratio 2.37, 95% confidence interval 1.48-3.78; p < 0.001). CGA is a valid tool to prospectively identify frail subjects among elderly patients with DLBCL.
Order of Authors: Carlo L Balduini; Luigi Gugliotta; Mario Luppi; Luca Laurenti; Catherine Klersy; Carla Pieresca; Gerlando Quintini; Francesco Iuliano; Rossana Re; Pierangelo Spedini; Nicola Vianelli; Alfonso Zaccaria; Enrico M Pogliani; Roberto Musso; Enrico Bobbio Pallavicini; Giovanni Quarta; Piero Galieni; Alberto Fragasso; Gianluca Casella; Patrizia Noris; Edoardo Ascari Abstract: Therapeutic plasma exchange (PE) is the accepted therapy for thrombotic thrombocytopenic purpura (TTP). Because not all patients obtain remission, other treatment modalities have been used in addition to PE, but no randomized clinical trial evaluated their efficacy. The aim of this multicentric study was to compare the effectiveness of standard-versus high-dose methylprednisolone as an adjunctive treatment to PE in the acute phase of TTP. Sixty patients with idiopathic TTP were randomized to receive standard-dose (1 mg/kg/die i.v.) or high-dose methylprednisolone (10 mg/kg/die for three days, thereafter 2.5 mg/kg/die) in addition to PE. Both dosages of steroids were well tolerated. At the end of induction therapy (day 23), the percentage of patients failing to obtain complete remission was significantly higher in the standard-dose (16/30) than in the high-dose group (7/30). Also the number of cases without a good response at day 9 and the number of deaths were higher in the standard-dose arm, but the differences did not reach the statistical significance. Results of present study indicate that the association of PE with high-dose instead of standard-dose steroids reduces the percentage of TTP patients that fail to achieve complete remission.Response to Reviewers: Reviewer #1: The authors have proved that the association of plasma exchanged with high-dose methylprednisolone instead of standard-dose reduces the percentage of TTP patients that failed to achieve complete remission. This observation has important clinical implication. I have no major remarksMinor remarks: Activity of ADAMTS 13 and autoantibodies against ADAMTS 13 were not tested. In my opinion this paper can be published in Annals Of Hematology in the present form.Reviewer #2: General:In this randomized clinical trial Balduini and colleagues compared low-dose vs. high dose steroids as an adjunctive treatment to plasma exchange with fresh frozen plasma / cryosupernatant in 60 patients suffering from acute TTP. In the low-dose arm more patients (13/30 vs. 7/30, p= 0.17) failed to achieve a good response at day 9 (primary endpoint of the study) and also more patients failed to achieve complete remission (16/30 vs. 7/30; p= 0.03). Also the number of death (4 vs. 1) was higher, this was however not statistically significant. The authors conclude that plasma exchange in combination with high dose steroids is superior to low-dose steroids. Over the years the Italian TTP study group has been able to conduct several randomized clinical trials in the setting of acute TTP addressing open questions in the field where many other groups have failed to do likewise due to lack of sui...
We conducted a prospective study to compare epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab (R-miniCEOP) with cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab (R-CHOP) for the treatment of "fit" elderly patients with diffuse large B-cell lymphoma (DLBCL). Patients over the age of 65 with stage II-IV DLBCL were screened with a comprehensive geriatric assessment. Patients were randomized to receive six courses of R-miniCEOP (n = 114) or R-CHOP (n = 110). Overall, the rate of complete remission was 70% (p = 0.466). After a median follow-up of 42 months, 5-year event-free survival (EFS) rates were 46% and 48% for R-miniCEOP and R-CHOP, respectively (p = 0.538). Patients older than 72 years and with low-risk disease had a better outcome when treated with R-miniCEOP (p = 0.011). Overall R-CHOP and R-miniCEOP are similarly effective for elderly "fit" patients with DLBCL. The less intense R-miniCEOP may be an acceptable option for the treatment of relatively older patients with low-risk disease.
Several trials comparing the efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in elderly patients with multiple myeloma (MM) have been reported, with inconsistent results. The primary goal of our study was to evaluate the efficacy and toxicity of MP versus MPT in newly diagnosed patients with MM who were transplant-ineligible or over age 65. A total of 135 patients were enrolled. Either minimal response or better or partial response or better were more frequent with MPT treatment (p = 0.001). After a median follow-up of 30 months, median progression-free survival (PFS) and overall survival (OS) were 33 and 52 months for MPT versus 22 and 32 months for MP, respectively. The comparison showed a significant advantage for MPT versus MP in PFS (p = 0.02) and only a trend for OS (p = 0.07). Severe adverse events were observed more frequently with MPT. In conclusion, our results show an improved activity of MPT at a cost of increased toxicity. We believe that MPT can be considered one of the new standard of care for elderly or transplant-ineligible patients with MM.
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