Patients with primary central nervous system lymphoma (PCNSL), a rare, aggressive form of lymphoma, typically have short survival rates. Certain pharmaceutical agents that can cross the blood-brain barrier (BBB) have been shown to significantly improve survival rates, but neurological toxicity and other adverse effects still remain. Results of a phase II trial found that a combination of rituximab and chemotherapy without radiation may be a safer alternative for patients with PCNSL.
Researchers from Johns Hopkins University in Baltimore, the Eastern Cooperative Oncology Groups and the American College of Imaging Network (ECOG-ACRIN) analyzed the toxicity and efficacy of rituximab and chemotherapy for patients with PCNSL to see if it was a safer treatment modality. They researchers wrote that although rituximab cannot cross the BBB, like high-dose methotrexate (HD-MTX), it has been found in cerebrospinal fluid and demonstrated remissions sustainability in these patients. The study was published in Oncotarget.
Blood-brain barrier. (Source: Creative Commons)
The researchers analyzed 25 patients who were newly diagnosed with PCNSL, had documented non-Hodgkin lymphoma (NHL) in the central nervous system, and had not received any previous radiotherapy or chemotherapy for their disease. Their ages ranged from 30 to 76 years old and nine of the patients had an ECOG score of 2 or 3.
Patients underwent a series of treatments consisting of:
HD-MTX with leucovorin rescue and vincristine (1.4 mg/m2 in weeks 1, 3, 5, 7, 9)
Rituximab (375 mg/m2 three times per week in weeks 1-4)
Procarbazine (100 mg/m2 daily for seven days in weeks 1, 5, 9)
Cytarabine (3g/m2 daily for two days in weeks 11, 14)
Dexamethasone (16 mg daily in week 1, 4mg/week in weeks 2, 3, 2mg/week in weeks 4-6)
Intrathecal MTX with leucovorin rescue for patients with CSF involvement (12 mg every two weeks in weeks 2, 4, 6, 8, 10).
The researchers found that 63% of patients reached two-year progression-free survival and 80% of patients had an overall response rate.
They were treated from four to 19 weeks and only 64% of patients completed their treatment due to adverse effects or disease progression, according to the study. The most common grade 3-4 AEs were hematologic (64% neutropenia, 52% lymphopenia, 32% hypokalemia, 20% anemia). Four of the patients stopped treatment due to adverse effects related to bowel perforation, acute renal failure, and two other reasons that were not listed.
“The results of this phase II trial demonstrated the potential use of rituximab and conventional chemotherapy as a treatment modality for PCNSL,” the authors wrote. They recommended the combined use of rituximab and chemotherapy as a safer regimen due to a decreased risk of neurotoxicological AEs.