Consolidation Therapy in Primary Central Nervous System Lymphoma

Primary central nervous system lymphoma is a complex disease with no agreed-upon standard-of-care therapy. Induction therapy involves multiagent chemotherapy based on high-dose methotrexate, with several regimens available. We have a preference for a regimen using rituximab, methotrexate (3.5 g/m2), procarbazine, and vincristine (R-MPV) for initial induction therapy, given the favorable balance between toxicities and very high response rates (80-90%), which allow for decreasing disease burden and increasing the effectiveness of consolidation treatments. However, in the absence of consolidation therapies, R-MPV is not an effective regimen to achieve long-term remission.Based on high rates of long-term remission, our first choice for consolidation therapy is high-dose chemotherapy with autologous stem-cell transplant using thiotepa, busulfan, and cyclophosphamide as a myeloablative regimen, with a curative intent. This typically applies to patients with a favorable performance status at the end of induction, typically with ECOG performance status of 2 or better, adequate organ function, and age younger than 70. Patients with a high transplant-related mortality risk may still be considered for milder myeloablative regimens such as carmustine/thiotepa.For patients who are not transplant candidates, we typically offer consolidation with reduced dose whole-brain radiation therapy (WBRT) (23.4 Gy), which seems to be associated with lower risks of neurotoxicity as compared with higher doses of radiation. For patients who are not transplant candidates and that do not accept the risk of cognitive decline from the radiotherapy, we typically offer consolidation high-dose cytarabine, provided the patient understands the high risk of relapse. For these patients, a clinical trial is strongly recommended.