<p>Systemic Approach to Recurrent Primary CNS Lymphoma: Perspective on Current and Emerging Treatment Strategies</p>

Abstract

There is no uniform standard of care for the treatment of refractory or recurrent primary central nervous lymphoma (r/r PCNSL). Many different systemic treatment regimens have been studied, but available data are based on small prospective or retrospective reports. There have been no randomized controlled trials in r/r PCNSL to date. Here, we provide an overview of published systemic regimens for the treatment of r/r PCNSL, as well as therapies that are under investigation. In addition, based on available data, we propose strategies of how to approach choice of therapy for different groups of patients in this disease setting. Patients can be mainly divided into three groups: 1) patients suitable for a re-challenge with high-dose methotrexate (HD-MTX)-based regimens and that may or may not be candidates for consolidation with high-dose chemotherapy with autologous stem cell transplant, 2) patients refractory to HD-MTX or that had early relapse, but suitable for an aggressive treatment strategy with re-induction with non-MTX-based therapy, possibly followed by high-dose chemotherapy with autologous transplant, and 3) patients not suitable for re-treatment with HD-MTX and that are not candidates for aggressive therapy. As PCNSL is a rare disease and as there is urgent need for better outcomes in r/r PCNSL, clinical trial participation is encouraged, especially in elderly or frail patients who are not candidates for high-dose chemotherapy and transplant.

Systemic Relapse in a Young Adult Patient with Primary CNS Diffuse Large B-Cell Lymphoma

“…In PCNSL, 8 patients responded, including 6 patients achieving CR [ 46 ]. However, the durability of response to this regimen is unknown since responding patients were allowed treatment with ASCT consolidation [ 57 ]. Immunomodulatory drugs (IMiDs), which inhibit NF-K β activity, include lenalidomide and pomalidomide [ 57 ].…”

Relapsed and refractory primary CNS lymphoma: treatment approaches in routine practice

“…Although it is pragmatic to include both groups of patients together in clinical trials due to the rarity of the tumor, combining the two entities poses a risk of premature determination of futility in early phase studies due to the significant inherent difference in biology and clinical outcomes. Although there is a lack of consensus, some authors have used the term ref-PCNSL to refer to disease that progresses during first line HD-MTX-based therapy or within the first 6 months of an initial response, whilst rel-PCNSL describes disease relapse following a sustained period of CR after first line therapy ( 24 ). It is estimated that 10-15% of newly diagnosed PCNSL are refractory to HD-MTX based therapies and inherently have more aggressive disease ( 25 , 26 ).…”

“…The responses were all PRs with no patients remaining free of progression over 6 months (median PFS 3 months) suggesting very limited efficacy of HD-AraC as monotherapy in rrPCNSL ( 51 ). Similarly, other retrospective studies have assessed cytotoxic agents such as topotecan, bendamustine, gemcitabine and oxaliplatin that, in general, confer sub-optimal and short-lived responses ( 24 , 30 ).…”

The Role of Rituximab in the Treatment of Primary Central Nervous System Lymphoma

“…This treatment has improved prognosis, but patient outcomes remain poor as compared to other forms of extranodal diffuse large B-cell lymphoma [ 15 , 16 ]. There is no consensus on the approach for relapsed PCNSL disease [ 17 , 18 ].…”