ASH: Adding Intrathecal Rituximab to R-DHAP + ASCT Feasible for Relapsed CNS Lymphoma

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ATLANTA—Combining the standard R-DHAP regimen plus autologous stem cell transplantation (ASCT) for relapsed diffuse large B-cell lymphoma (DLBCL) with intrathecal rituximab and high-dose IV methotrexate (MTX) is feasible for the treatment of secondary central nervous system (CNS) lymphoma, investigators reported during the 54th American Society of Hematology Annual Meeting and Exposition.

Overall, the prognosis of patients with relapsed DLBCL and CNS involvement is poor, with a median survival of 2 to 4 months and 1-year survival of <10%, noted Jeanette K. Doorduijn, MD, PhD, Department of Hematology, Erasmus MC, Rotterdam, Netherlands.

Between May 2007 and April 2011, 36 patients in the phase 2 HOVON study were treated with three cycles of R-DHAP-MTX (dexamethasone 40mg day 1-4; cisplatin 100mg/m2 day 1; cytarabine 2 x 2g/m2 Day 2; rituximab 375mg/m2 day 1; and MTX 3g/m2 day 15). Intrathecal rituximab 10mg was scheduled on day 0, followed by 25mg on days 4, 8, 11, and 21 during the first cycle and given in four and three administrations during cycle 2 and 3, respectively. Patients who failed to clear the CSF at the start of cycle 2 could switch to intrathecal MTX/cytarabine/dexamethasone.

Patients with at least a partial response (PR) and no evidence of lymphoma in bone marrow and CSF after cycle 2 had stem cells harvested after the third R-DHAP cycle; MTX was administered during cycle 3 along with consolidation with busulfan/cyclophosphamide and ASCT. After 2 cycles of systemic and intrathecal therapy, CNS response (based on CSF and MRI) was complete response (CR) in 10 patients and PR in 13 patients.

Overall response rate was 53% and CR rate was 19%, with 15 patients (42%) completing treatment according to protocol. Median response duration is 6 months. Median overall survival was 7 months. At 1 year, PFS is 25% (95% CI 9-34%), and OS, 25% (95% CI 12-40%).

After 13 patients were treated, 3 experienced a temporary severe painful radiculopathy after the first intrathecal injection with rituximab 25mg. “Therefore, the study was amended and the dose of all intrathecal rituximab administrations was reduced to 10mg,” Dr. Doorduijnreported.

Of the 36 patients, 20 died due to non-Hodgkin lymphoma; other causes of death were excessive toxicity (n=2), intercurrent death (n=2), other (n=2) , and unknown (n=2).

However, despite these results, “the outcome of secondary CNS lymphoma following high-dose chemotherapy remains poor,” she concluded.

Intrathecal rituximab is not approved for the use outlined in this study.

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