Aids Related Primary Central Nervous System Lymphoma Is Still a Challenge in the Cart Era: A Single Centre Experience

Introduction. Aids Related Primary Central Nervous System Lymphoma (AR-PCNSL) is an aggressive entity, with a markedly inferior prognosis to PCNSL in immunocompetent. The introduction of combination antiretroviral therapy (cART) has substantially reduced the incidence of AR-PCNSL, but sporadic cases of AR-PCNSL continue to represent a therapeutic challenge and there is little information to guide clinical management for these patients (pts). To evaluate the chance of cure of AR-PCNSL in the cART era, we retrospectively analyzed outcomes of all AR-PCNSL diagnosed and treated at our center, a public hospital with history of dedicated care for Aids Related-lymphoma (AR-ly).

Patients and Methods. Since 1985, all pts with AR-ly diagnosed at our center are prospectively recorded in a database. Data concerning AR-PCNSL were extracted and electronic medical records and physical charts were also revised. Inclusion criteria required diagnosis of SNC non Hodgkin lymphoma (NHL) in the absence of preceding or concomitant systemic lymphoma. Demographic, HIV-and lymphoma-related characteristics were analysed, as well as treatment and outcome.

Results. Among 231 HIV positive pts with aggressive NHL diagnosed between 1985-2016, 26 pts with AR-PCNSL were identified and included in this analysis. Diagnosis was histologically or cytologically confirmed in 25. Fourteen pts were diagnosed between 1987-1996 (pre-cART era) and 12 between 1997-2016 (post-cART era). The proportion of pts with AR-PCNSL decreased from 14.4% to 9% after the advent of cART. During the pre-cART era, the median time from HIV and AR-PCNSL diagnosis was 27.5 mo (6-126) and median CD4 count 24.5/mcl (1-136). Eleven pts had prior opportunistic infections. Due to early deaths and poor PS, only 3 pts could receive specific treatment for NHL (2 whole brain radiotherapy, WBRT, and 1 unspecified chemotherapy); the pt treated with chemotherapy died after few months due to liver and heart failure. The 2 pts who received WBRT died early (ischemic heart failure and unknown cause) without evidence of response. The median overall survival (OS) of AR-PCNSL in the pre-cART era was only 2 mo (1-5). During the post-caART era HIV and AR-PCNSL diagnoses were consensual in 4/12 pts (33%). Among the others, 4/8 pts were on cART at AR-PCNSL onset and 6/8 pts had already experienced one or more opportunistic complications. The median time from HIV and AR-PCNSL diagnosis was 46 mo (0-272) and median CD4 count was 39/mcl (12-1044). Of 12 pts diagnosed in the post-cART era, 3 died before receipt of any intervention and 5 received only cART because of advanced disease, poor PS and comorbidity. Four pts received CNS NHL directed therapy, in combination with cART. One pt received WBRT and 3 received HD-MTX-based chemotherapy (dose 3-3.5 gr/sm, for 1-2 cycles). Overall, a CR was documented in 2 pts (1 after WBRT and 1 after cART alone) and a partial remission (PR) in 2 (1 after HD-MTX-based therapy and 1 after cART alone). All other pts progressed and died early from NHL (1 pt failed both HD-MTX therapy and WBRT). As a result, the OS remained extremely poor even in the cART era in the whole group of pts (median OS 2.5 mo, 1-118), and was 5 mo (2-10) in the 4 pts who received CNS NHL directed therapy. The only 2 pts alive at the time of this analysis are those obtaining a CR (at mo +118 and +10). Notably, the long survivor pt received only cART for CNS NHL; however, 16 mo later he developed a systemic plasmablastic lymphoma which was successfully treated. Of the 3 pts receiving HD-MTX-based therapy, 2 (1 with plasmablastic histology) progressed during treatment and 1 with CD4 1044/mcl, receiving HD-MTX/ARA-C + Thiotepa + Rituximab, achieved PR after 2 cycles, but lymphoma progressed after treatment suspension due to neurologic and infectious toxicity.

Conclusions: Treating patients with AR-PCNSL remains a challenge even in the cART-era, especially for delayed diagnosis, poor clinical conditions and severe immunodeficiency. A prompt diagnosis and effective cART are highly desirable. We can not recommend a specific therapeutic strategy from our experience. However, due to the favourable results observed in the HIV negative setting, the role of HD-MTX integrated with cART deserves prospective evaluation in order to identify clinical benefit and potential toxicity. Similarly, innovative approaches, including lenalidomide and ibrutinib, might also be considered for their favourable safety profile.