A 2-Stage Phase II study of panobinostat consolidation in myeloma patients with < CR following high-dose chemotherapy (HDT) conditioned autologous stem cell transplantation (ASCT)

2015 ◽  
Vol 15 ◽  
pp. e132
Author(s):  
A. Kalff ◽  
T. Khong ◽  
S. Mithrapabhu ◽  
P. Walker ◽  
A. Chow ◽  
...  
2006 ◽  
Vol 24 (24) ◽  
pp. 3865-3870 ◽  
Author(s):  
Gerald Illerhaus ◽  
Reinhard Marks ◽  
Gabriele Ihorst ◽  
Roland Guttenberger ◽  
Christoph Ostertag ◽  
...  

Purpose To improve survival and reduce toxicity in primary CNS lymphoma (PCNSL) treatment, we conducted a multicenter phase II study with early high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) followed by hyperfractionated whole-brain radiotherapy (WBRT) for newly diagnosed PCNSL patients younger than 65 years of age. Patients and Methods Chemotherapy included three steps: three cycles of methotrexate (8 g/m2); cytarabine (AraC; two doses of 3 g/m2) and thiotepa (40 mg/m2) followed by stem-cell harvest; HDT with carmustine (400 mg/m2) and thiotepa (two doses of 5 mg/kg body weight) followed by ASCT. WBRT (45 Gy, two doses of 1 Gy/d) was administered for consolidation. Results Thirty patients with PCNSL younger than 65 years of age (median, 54 years; range, 27 years to 64 years) were enrolled (nine pilot-phase; 21 phase II). Twenty-eight patients responded to methotrexate: six patients with complete remission (CR), 15 patients with partial remission (PR), and seven patients with stable disease (SD) with clinical improvement. Of 26 patients proceeding to AraC and thiotepa, 10 patients achieved CR, 14 patients achieved PR, one patient experienced SD with clinical improvement, and one patient suffered disease progression. Twenty-three patients received HDT plus ASCT, resulting in 15 patients with CRs and eight patients with PRs. After WBRT, 21 of 21 patients had CRs. One patient died from liver failure after methotrexate. HDT was well tolerated apart from WHO grade 3/4 cytopenia. With a median follow-up of 63 months (range, 4 months to 84 months), 5-year overall survival probability is 69% for all patients and 87% for the 23 patients receiving HDT plus ASCT. The 5-year probability of relapse-related death is 21% for all patients (n = 30) and 8.7% for patients treated with HDT plus ASCT (n = 23). Conclusion Sequential systemic methotrexate and AraC and thiotepa followed by HDT plus ASCT and hyperfractionated WBRT is very effective with little toxicity as initial therapy for PCNSL.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8031-8031 ◽  
Author(s):  
Agnieszka Korfel ◽  
Gerald Illerhaus ◽  
Mathias Haenel ◽  
Robert Moehle ◽  
Roland Schroers ◽  
...  

8031 Background: The outcome of patients with CNS relapse of aggressive lymphoma (secondary CNS lymphoma, SCNSL) is poor with no standard therapy established thus far. Here we present the final analysis of a prospective multicenter phase II study using an intensive induction regimen followed by high-dose chemotherapy and autologous stem-cell transplantation. Methods: Adult immunocompetent patients ≤65 years with SCNSL were eligible. Induction chemotherapy consisted of two cycles MTX/IFO (methotrexate 4g/m2 iv. d1, ifosfamide 2g/m2 iv. d3-5 and i.th. liposomal cytarabine 50mg d6) and one cycle AraC/TT (cytarabine 3g/m2 d1-2, thiotepa 40mg/m2 iv. d2 and i.th. liposomal cytarabine 50mg d3). Then, patients without progression received high-dose chemotherapy with carmustine 400mg/m2 iv. d -5, thiotepa 2x5mg/kg iv. d -4 to -3 and etoposide 150mg/m2 iv. d -5 to -3 followed by ASCT d0. Results: Thirty eligible patients (median age 58 years) were enrolled. Three patients had T-cell and 27 aggressive B-cell lymphoma. Pre-treatment was CHOP-like in 29 patients, including rituximab in 26. CNS relapse occurred after a median of 8.5 (3-80) months and was intracerebral in 23 and meningeal in13 patients (combined in 7); 6 had concomitant systemic lymphoma. After induction therapy CNS response was found in 22 (73%) patients (8xCR, 14xPR), 3 patients had SD, 4 patients PD and 1 patient no response evaluation. HD-ASCT was performed in 24 patients; resulting in 15 CR (63%), 2 PR (8%) and 7 PD (29%). Myelotoxicity was the most frequent WHO grade 3-4 adverse event with infections in 8/30 pts on MTX/IFO (27%), 5/23 (22%) on AraC/TT and 11/20(55%) on HD-ASCT. One patient died due to septic diverticulitis and one developed persisting fecal incontinence. The median follow up was 21 months. The median PFS was 12.1 months (95% CI 6.4-17.7) in all patients and 30.4 (95%CI 2.5-58.3) months after HD-ASCT, the median overall survival was 27.4 months and not reached, respectively. Conclusions: This first prospective study on SCNSL demonstrates that lasting remissions can be achieved with CNS-directed HD-ASCT in a large proportion of patients and probably cure in some.


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