[Abstract] Primary CNS Lymphoma; A Review of the University of Michigan Experience 2004-2013

Abstract

Background: Evidence supports high dose methotrexate (HD-MTX), rituximab, and cytarabine treatment for newly diagnosed primary CNS lymphoma (PCNSL), but no regimen is standard. Since 2004, the University of Michigan treatment regimen has been 8 cycles of HD-MTX (8 g/m2), rituximab 375 mg/m2, vincristine 2 mg (cycles 1-5), cytarabine 1.5-3 g/m2 (cycles 4-8) with 6 cycles of temozolomide consolidation, 150-200 mg/m2 days 1-5 of 28. Radiation is reserved for patients without a complete response (CR).

Methods: We conducted an IRB-approved review of all patients with newly diagnosed PCNSL treated at the University of Michigan from 1/1/04 – 12/31/2013. Patients with absent/inconclusive pathology, a history of high-grade systemic lymphoma, or organ transplant were excluded. Immunosuppression with no transplant history was allowed. No performance status cutoff was employed. All patients initiating treatment were included in the analysis. MRI was reviewed to determine overall response, date of complete response (CR), and date of progression. Survival endpoints were estimated from time of diagnosis, and were analyzed using PROC LIFETEST in SAS v9.4.

Results: 57 patients, median age of 66 (range 43-85), were identified. 38 (67%) had CR at completion of HD-MTX. Median overall survival (mOS) was 5.25 years (95% CI 2.14, ∞). Median progression free survival (mPFS) was 1.94 years (1.41, ∞). In the CR group, mPFS was 6.02 years (1.89, ∞), 2-year PFS 65% (46,78), and 3-year PFS 53% (34,69). Also in the CR group, mOS was not reached, 2-year OS 83% (65,92), and 3-year OS 62% (43,77). Median follow up in the CR group was 3.87 years. Presently, 22 patients with CR, and 33 patients overall, are alive without progression.

Conclusions: The University of Michigan PCNSL regimen shows response rates, response duration, and survival outcomes comparable to the more efficacious published regimens. Advantages of this regimen include use early in treatment of drugs with low passage across the blood-brain barrier, applicability to nearly all patients with CNS lymphoma, and avoidance of radiation with its attendant long-term toxicity. Strengths of this study include the large number of patients and inclusion of patients with a wide range of age and functional status.

Nicholas J. Seewald

Assistant Professor of Biostatistics

Assistant Professor of Biostatistics at the University of Pennsyvlania Perelman School of Medicine