Acute Painful Radiculopathy After Intrathecal Rituximab

Abstract 4920

Within a prospective phase II study (HOVON 80) of patients with recurrent diffuse large B-cel lymphoma in the CNS, three of 13 patients treated with intrathecal rituximab developed an acute, transient, extremely painful lumbosacral radiculopathy. All were treated with systemic R-DHAP every 4 weeks with i.v. HD-MTX on day 15 for three cycles. In addition intrathecal Rituximab was administered twice weekly via lumbar puncture starting on day -1. According to protocol the first administration consisted of 10 mg of rituximab after premedication with acetaminophen, thereafter the dose was increased to 25 mg. No patient experienced side effects of the first intrathecal administration of rituximab. However, after the first administration of 25 mg rituximab three of 13 treated patients reported extremely painful tingling sensations in the buttocks, legs and feet immediately after administration and lasting 30–60 minutes. Concomitantly a temporarily increased bloodpressure was documented. Premedication with an antihistaminic in the third patient was ineffective. No neurologic deficits occurred and the pain resolved completely. The patients refused further treatment with intrathecal rituximab, and therapy was changed to intrathecal methotrexate, without any side effects. After these events the rituximab was diluted in saline to 5 mg/ml, the dose reduced to 10 mg per administration, and 4 mg dexamethasone was administered concomitantly in all subsequent patients. Twelve additional patients were thus treated and no further incidents of painful radiculopathy were observed. This serious, though completely transient, adverse effect of intrathecal rituximab precludes intrathecal administration of higher doses of rituximab via lumbar route. It has never been described after intraventricular administration.