Immunochemotherapy with Intensive Consolidation for Primary CNS Lymphoma: A Pilot Study and Prognostic Assessment by Diffusion-Weighted MRI

Abstract

Purpose We evaluated a novel therapy for primary central nervous system (CNS) lymphoma (PCNSL) using induction immunochemotherapy with high-dose methotrexate, temozolomide and rituximab (MT-R) followed by intensive consolidation with infusional etoposide and high-dose cytarabine (EA). In addition, we evaluated the prognostic value of the minimum apparent diffusion coefficient (ADCmin) derived from diffusion-weighted magnetic resonance imaging (DW-MRI) in patients treated with this regimen. Experimental Design Thirty-one patients (median age, 61; median KPS, 60) received induction with methotrexate every 14 days for 8 planned cycles. Rituximab was administered the first 6 cycles and temozolomide administered on odd-numbered cycles. Patients with responsive or stable CNS disease received EA consolidation. Pretreatment DW-MRI was used to calculate the ADCmin of contrast-enhancing lesions. Results The complete response rate for MT-R induction was 52%. At a median follow-up of 79 months, the 2-year progression-free and overall survival were 45% and 58%, respectively. For patients receiving EA consolidation, the 2-year progression-free and overall survival were 78% and 93%, respectively. EA consolidation was also effective in an additional 3 patients who presented with synchronous CNS and systemic lymphoma. Tumor ADCmin <384 × 10−6 mm2/s was significantly associated with shorter progression-free and overall survival. Conclusions MT-R induction was effective and well-tolerated. MT-R followed by EA consolidation yielded progression-free and overall survival outcomes comparable to regimens using chemotherapy followed by whole-brain radiotherapy consolidation but without evidence of neurotoxicity. Tumor ADCmin derived from DW-MRI provided better prognostic information for PCNSL patients treated with the MTR-EA regimen than established clinical risk scores.

The diagnostic role and dynamic changes in cerebrospinal fluid neopterin during treatment of patients with primary central nervous system lymphoma

“…Once the diagnosis of PCNSL is confirmed, high‐dose methotrexate should be promptly administered as the first‐choice treatment. In addition, methotrexate in combination with other chemotherapeutic agents,41 autologous stem cell transplantation,42, 43 or rituximab44, 45 have been found to improve prognosis of patients with PCNSL.…”

Successful Treatment of Elderly Diffuse Large B-Cell Lymphoma with Central Nervous System Recurrence by Rituximab, Ranimusutine, Ifosfamide, Procarbazine, Dexamethasone, and Etoposide Therapy

“…Bimbaum et al recently reported the benefits of rituximab in addition to MTX and IFO over MTX and IFO in 36 cases of primary CNS lymphoma in a retrospective analysis [6]. In prospective study, some investigators described promising response rate and survival in primary CNS lymphoma by multi-agent chemotherapy including rituximab as induction therapy [4, 5,7]. Therefore, intravenous administration of rituximab for CNS recurrence in systemic DLBCL may be considered as a treatment option.…”

“…On the other hand, we did not use rituximab in the study [3]. Recently, regarding primary CNS lymphoma (PCNSL), intravenous rituximab in addition to combined chemotherapy has been accepted as the standard treatment strategy [4][5][6][7]. Furthermore, CNS recurrence of systemic DLBCL is usually premonitory symptom of systemic recurrence, therefore, administration of rituximab in the salvage therapy may be considered as prevention for systemic reoccurrence.…”

Treatment of Primary CNS Lymphoma

“…The 2-year OS was 58% when all patients were analyzed and 93% in the cohort of patients who had qualified for and received consolidation therapy with etoposide and cytarabine without evidence of neurotoxicity [45]. This regimen was further evaluated within a multicenter study resulting in survival curves which display evidence of a plateau.…”