OS curves of analyzed subgroups (i.e., age, prognostic scores).2,3,8 Updated results of the NABTT 96–07 trial have confirmed that late relapses also occur in patients with PCNSL treated with high-dose MTX alone, with only 20% of treated patients remaining relapse-free at a median follow-up of 6.8 years.9 In the present trial, all recorded events but 4 occurred within the first 5 years of follow-up. The 4 late events were 2 deaths due to brain relapse at 67 and 110 months, an unrelated death while disease-free at 63 months, and a systemic (extraneural) relapse at 100 months that was successfully managed with high-dose polychemotherapy. Followup is longer than 10 years in 8 of the 9 survivors, which could be synonymous of cure in PCNSL. In effect, although late relapses affected 21% of patients followed by more than 5 years in a prospective trial,3,8 relapses after 10 years have been exceptional events in

PCNSL, affecting 2 (0.7%) of 278 patients who had achieved CR after first-line treatment in an unselected retrospective series.5 Owing to the rarity of this event and the unchanged survival plateau after an extended follow-up, we are confident that long-term survivors after MATILDE-WBRT can be considered cured of PCNSL. This experience confirms that reporting of long-term follow-up outcome is crucial to fully evaluate the potential for definitive cure of PCNSL by a new chemotherapy regimen. AUTHOR CONTRIBUTIONS A.J.M.F. and M.R. designed and conceptualized the trial and the analysis, collected data, performed and interpreted statistical analysis, and wrote the manuscript. F.C., A.A.B., A.T., M.M., M.B., M.S., F.I., F.Z., C.S., F.B., G.C., and L.B. registered and treated patients and collected data.

STUDY FUNDING No targeted funding reported.

DISCLOSURE

Comment: Defining cure in primary CNS lymphoma

The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.

Primary CNS lymphoma (PCNSL), a type of extranodal non-Hodgkin lymphoma, is a potentially curable brain cancer. Ongoing randomized trials assessing treatments for PCNSL will ultimately establish a standard of care. Until that time, practitioners have multiple treatment options from which to choose. In this report, the authors provide long-term follow-up data from a phase 2 clinical trial in newly diagnosed PCNSL patients, ages 18–70, treated with MATILDE chemotherapy followed by whole-brain radiation therapy (WBRT).1 The MATILDE regimen, like all induction chemotherapy currently utilized for PCNSL, includes methotrexate, the single most effective agent against PCNSL. Following chemotherapy, patients received a consolidative WBRT dose based on their initial response to chemotherapy. Eight of 41 patients treated with MATILDE were alive .10 years from diagnosis and were likely cured of their lymphoma. Relative to the overall study population, these patients were younger and had better functional status at the time of initial PCNSL diagnosis. While detailed neuropsychological and quality of life status were lacking in these participants, only 1 long-term survivor had severely compromised cognition and 5 were working. It is noteworthy that these results are comparable to the proportion of long-term PCNSL survivors achieved using either less aggressive or more aggressive treatment regimens. As long-term survival is now feasible with several treatments for PCNSL, it is critical to employ regimens that minimize the risk of delayed neurotoxicity. To this end, there are neuropsychological instruments now available that are more useful in the assessment of delayed neurotoxicity than the Mini-Mental State Examination used in this report.2 Furthermore, given the potential for late relapse in PCNSL, all prospective clinical trials should routinely report 10-year follow-up results. Such reports, like the present one, will allow more accurate assessment of cure rates, delayed neurotoxicity, and quality of life. 1. 2.

Ferreri AJM, Ciceri F, Brandes AA, et al. MATILDE chemotherapy regimen for primary CNS lymphoma: results at a median follow-up of 12 years. Neurology 2014;82:1370–1373. Correa DD, Maron L, Harder H, et al. Cognitive functions in primary CNS lymphoma: literature review and assessment guidelines. Ann Oncol 2007;18:1145–1151.

Tracy T. Batchelor, MD From the Departments of Neurology and Radiation Oncology, Division of Hematology/Oncology, Massachusetts General Hospital and Harvard Medical School, Boston. Study funding: No targeted funding reported. Disclosure: T. Batchelor serves as a consultant or in an advisory role for Merck & Co., Inc., Roche, Kirin Pharmaceuticals, Spectrum, Champions Biotechnology, Advance Medical, Novartis, and Agenus; has received honoraria from Up to Date, Inc., Robert Michael Educational Institute LLC, Educational Concepts Group, Research to Practice, Imedex, Oakstone Medical Publishing, and American Society of Hematology; and receives research support from Pfizer, Astra Zeneca, Millennium, and NIH. Go to Neurology.org for full disclosures.

Received August 14, 2013. Accepted in final form December 29, 2013.

REFERENCES 1. Ferreri AJ. How I treat primary CNS lymphoma. Blood 2011;118:510–522. 2. Morris PG, Correa DD, Yahalom J, et al. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol 2013;31:3971–3979. 3. Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma–a long-term follow-up study. Ann Oncol 2012;23:2670–2675. 4. Ferreri AJ, Reni M, Pasini F, et al. A multicenter study of treatment of primary CNS lymphoma. Neurology 2002;58: 1513–1520. 5. Nayak L, Hedvat C, Rosenblum MK, Abrey LE, DeAngelis LM. Late relapse in primary central nervous system lymphoma: Clonal persistence. Neuro Oncol 2011;13:525–529. 6. Ferreri AJ, Dell’Oro S, Foppoli M, et al. MATILDE regimen followed by radiotherapy is an active strategy against primary CNS lymphomas. Neurology 2006;66:1435–1438. 7. Ferreri AJ, Blay JY, Reni M, et al. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol 2003; 21:266–272. 8. Illerhaus G, Marks R, Ihorst G, et al. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol 2006;24:3865–3870. 9. Gerstner ER, Carson KA, Grossman SA, Batchelor TT. Long-term outcome in PCNSL patients treated with highdose methotrexate and deferred radiation. Neurology 2008; 70:401–402.

Neurology 82

April 15, 2014

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Comment: defining cure in primary CNS lymphoma.

Primary CNS lymphoma (PCNSL), a type of extranodal non-Hodgkin lymphoma, is a potentially curable brain cancer. Ongoing randomized trials assessing tr...
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