Treatment Of Non-Hodgkin's Lymphoma With Secondary Central Nervous System Involvement: Encouraging Response Rates Using CNS-Penetrating Idaram Chemotherapy

• Published in: Blood 2013-11, Vol.122 (21), p.4367-4367
• Main Authors: Maciocia, Paul M, Badat, Mohsin, Cheesman, Simon, Lambert, Jonathan, Pule, Martin, Linch, David C., Ardeshna, Kirit M
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.4367.4367

Non-Hodgkin's lymphomas with secondary involvement of the central nervous system (CNS) typically carry a poor prognosis. There is limited data in the literature regarding the optimal therapy for these patients. IDARAM is a cytotoxic regimen which penetrates the CNS. It has demonstrated efficacy in early studies in secondary CNS lymphoma [Moreton et al, Cancer Chemother Pharmacol (2004) 53: 324–8]. We present here the largest series of patients with secondary CNS involvement treated with IDARAM+/- rituximab at University College Hospital London between June 2005 and January 2013. Thirty-eight patients were treated with 1-4 cycles of IDARAM, consisting of methotrexate 12.5mg by intrathecal injection day 1; idarubicin daily 10mg/m2 IV days 1 and 2; dexamethasone 100mg daily IV infusions of 12h duration days 1-3; cytosine arabinoside daily 1000mg/m2 IV over 1 hour days 1 and 2; and methotrexate 2000mg/m2 IV over 2 hours day 3. CSF was analysed for lymphomatous involvement by flow cytometry on D1. Patients with a clear CSF from the outset only received one intrathecal injection on day 1 of cycle 1. Most patients with B-cell lymphoma additionally received 1-2 doses of rituximab 375 mg/m2 IV on day 1 (+/- day 8) of each cycle. Baseline characteristics are presented in table 1. 16/38 (42%) patients had secondary CNS involvement at the time of initial diagnosis of NHL or within 2 months (‘New Diagnosis'). 22/38 (58%) had refractory (CNS involvement diagnosed in latter part of therapy or within 3 months of completion of primary therapy) or relapsed (CNS involvement diagnosed at relapse - either combined with a systemic relapse or isolated to CNS) disease. 84 cycles of IDARAM were delivered to 38 patients. Patients received a median of 2 cycles. 20/37 responded (overall response rate (ORR) = 54%) with 12/37 (32%) achieving a complete response and 8/37 (22%) a partial response (PR). Median progression-free survival (PFS) was 6.8 months and overall survival (OS) was 27.5 months. In patients with a ‘New' diagnosis ORR was 10/15 (67%) CR 7/15 (47%), PR 3/15 (20%), median PFS was 48 months, median OS has not been reached (see figure 1). Neither age nor performance score predicted outcome in these patients. Table 1Baseline characteristics of patientsParametern (%) or Median [Range]Male Gender22 (58)Age (Years)55 [25-71]Performance Status2 [0-4]High Grade Disease30 (79)B-Cell Lymphoma34 (89)Type of Diagnosis- New15 (40)- Relapsed16 (43)- Primary Refractory6 (16)CSF Involved