Treatment Efficacy and Outcomes in HIV-Related Plasmablastic Lymphoma: The Results of Multicenter Retrospective Study in Russia

Background

Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy highly associated with HIV. Despite improved understanding of this disease, its prognosis remains poor with short overall survival. There is no standard of care for this entity. Recent advances in the treatment of HIV-associated and aggressive lymphomas have not yet significantly improved the outcomes of patients with PbL.

Methods

We investigate epidemiological characteristics and the results of the treatment of the HIV-related PbL in large cohort of HIV-related lymphoma patients for a 7-year period (2014-2020). During the observation period, 22 cases of HIV-related PbL were registered in three centers and selected for the analysis from the national multicenter retrospective study database. The median follow-up was 17,8 (4-57,4) months.

Results

The PbL accounted for 8,9% of lymphomas in HIV-infected patients (22/247). The median age was 42 years (32-61), males - 9 (41%). Most of the patients (n=19, 86%) had III-IV stages and B-symptoms were present in 8 patients (36%). CNS involvement was diagnosed in 8 patients (36%). The median of ECOG score was I (I-III). Half of patients had viral hepatitis as a co-infection including HCV (n=9), HCV and HBV (n=1), HCV, HBV and HDV (n=1). HIV and lymphoma were diagnosed simultaneously in 7 patients (32%). Median time from HIV infection to the lymphoma onset was 4 years (1,5 month - 17,5 years). The only one patient did not receive cART for an unknown reason. The median number of CD4+ cells at the moment of chemotherapy (CT) started was 151 cell/mcl (13 - 374). Frontline CT were following: CHOP±E - 9 (41%), EPOCH - 11 (50%), hyper-CVAD - 1 (4,5%), dexamethasone - 1 (4,5%). Bortezomib was added to frontline treatment in 3 (13,6%) patients, HDC with auto-HSCT had been done as a first line therapy in 2 (9%) patients. A total of 16 patients responded to the first line therapy with the overall response rate (ORR) of 72,7% including CR and PR in 4 (18,2%) and 12 (54,5%) patients respectively. Remaining patients had progression disease (n=5, 22,8%) and stable disease (n=1, 4,5%). The median course to achieve the ORR was 4 (2-6) cycles. Overall (OS) and progression-free survival (PFS) at 2 years after first line treatment was 59,1% and 40,9%, respectively. The median time to progression (TTP) was 7,95 (0,33-23,93) months. The addition of bortezomib and auto-HSCT in first line chemo improved OS (100% vs 47,1%, p=0,027), but non PFS (p=0,1) and TTP (p=0,4). Nine patients received second-line CT: DHAP - 4 (44,4%), ICE - 4 (44,4%), EPOCH - 1 (11,2%). Response was evaluated in 8 patients. CR, PR and progression disease was registered in 1 (12,5%), 2 (25%) and 5 (62,5%) patients respectively. PBSC harvesting was only successful in 1 of 3 cases (33%) and this patient received HDC with auto-HSCT. OS and PFS at 2 years after second line treatment was 44,4% and 22,2%, respectively. Two years after second line CT, 4 patients were still alive, including those after ICE, EPOCH (n=2), HDC with auto-HSCT (n=1) and nivolumab (27 cycles) as a third line therapy (n=1).

Conclusions

In a large cohort of patients PbL accounted for 8.9% of all HIV-related lymphomas. Bortezomib-containing chemotherapy and first line auto-HSCT show encouraging results, but data are obtained in a small group of patients. Prospective studies are needed for optimization of HIV-related plasmablastic lymphoma therapy.