Treatment Regimens for Immunocompetent Elderly Patients with Primary Central Nervous System Lymphoma: A Scoping Review

SIMPLE SUMMARY: Most patients diagnosed with primary central nervous system lymphoma (PCNSL) are 60 years or older and tend to have a poor prognosis. Evidence to guide and optimize treatment choices for these vulnerable patients is limited. We performed a scoping review to identify and describe all relevant clinical studies investigating chemotherapies and combinations of chemotherapies (including high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT)) in elderly PCNSL patients. In total, we identified six randomized controlled trials, 26 prospective and 24 retrospective studies (with/without control group). While most studies investigated protocols based on ‘conventional’ chemotherapy treatment, data evaluating HCT-ASCT in the elderly were scarce, and the generalizability of the only RCT published is questionable. Considering the poor prognosis of these patients and their need for more effective treatment options, a thoroughly planned randomized controlled trial comparing HCT-ASCT with ‘conventional’ chemoimmunotherapy is urgently needed to evaluate the efficacy of HCT-ASCT. ABSTRACT: Background: Most patients diagnosed with primary central nervous system lymphoma (PCNSL) are older than 60 years. Despite promising treatment options for younger patients, prognosis for the elderly remains poor and efficacy of available treatment options is limited. Materials and Methods: We conducted a scoping review to identify and summarize the current study pool available evaluating different types and combinations of (immuno) chemotherapy with a special focus on HCT-ASCT in elderly PCNSL. Relevant studies were identified through systematic searches in the bibliographic databases Medline, Web of Science, Cochrane Library and ScienceDirect (last search conducted in September 2020). For ongoing studies, we searched ClinicalTrials.gov, the German study register and the WHO registry. Results: In total, we identified six randomized controlled trials (RCT) with 1.346 patients, 26 prospective (with 1.366 patients) and 24 retrospective studies (with 2.629 patients). Of these, only six studies (one completed and one ongoing RCT (with 447 patients), one completed and one ongoing prospective single arm study (with 65 patients), and two retrospective single arm studies (with 122 patients)) evaluated HCT-ASCT. Patient relevant outcomes such as progression-free and overall survival and (neuro-)toxicity were adequately considered across almost all studies. The current study pool is, however, not conclusive in terms of the most effective treatment options for elderly. Main limitations were (very) small sample sizes and heterogeneous patient populations in terms of age ranges (particularly in RCTs) limiting the applicability of the results to the target population (elderly). Conclusions: Although it has been shown that HCT-ASCT is probably a feasible and effective treatment option, this approach has never been investigated within a RCT including a wide range of elderly patients. A RCT comparing conventional (immuno) chemotherapy with HCT-ASCT is crucial to evaluate benefit and harms in an un-biased manner to eventually provide older PCNSL patients with the most effective treatment.