Sustained response following BTK inhibitors based treatment in HIV-related primary central nervous system lymphoma: case report

Abstract

Background: Despite increasing effort for treating primary central nervous system lymphoma (PCNSL), the prognosis of human immunodeficiency virus (HIV) -related PCNSL was still unsatisfactory. There is currently a lack of clinical evidence for the application of Bruton tyrosine kinase (BTK) inhibitor in HIV-related PCNSL. We reported two HIV-related PCNSL patients, who achieved sustained remission by application of BTK inhibitor based treatment. This protocol had not been previously reported for the treatment of HIV-related PCNSL.

Case presentation: The two cases were characterized by the treatment choice of Bruton tyrosine kinase (BTK) inhibitor. Rituximab was not recommended for them due to their very low CD4⁺ T cell counts. They both took MTX as the first-line therapy and got a relief in initial phase. For the first case, ibrutinib was kept both in the first-line therapy and in the maintenance therapy. When the second case underwent a progressive disease, we continued to use orelabrutinib as one of the salvage treatment, in combination with programmed cell death-1 (PD-1) inhibitor plus lenalidomide. They both achieved a continuous response of up to 20 months without opportunistic infection.

Conclusions: This report highlights the safety and effectiveness of BTK inhibitors, as well as lenalidomide and PD-1 inhibitor in HIV-related PCNSL patients. Both the new therapeutic approaches and a multidisciplinary team authentically contributed to improved survival outcome among HIV-positive PCNSL patients.

Keywords: Bruton tyrosine kinase inhibitor; Human immunodeficiency virus; Primary central nervous system lymphoma.

Fig. 1

The radiological, pathologic diagnosis and treatment of case 1. Brain contrast-enhanced MRI (a-d): A space-occupying lesion about 3.9 × 2 × 1.6 cm at the corpus callosum with a ring enhancement before treatment (in Apr, 2021) (a); Having a partial response (PR) after 2 months treatment (In August, 2021) (b); Keeping a PR after 4 months treatment (In October, 2021) (c); Achieving a complete response (CR) after 8 months treatment (In March, 2022) and keeping a CR after 19 months treatment (In February, 2023) (d). Histological characteristics (e-h): Diffuse distribution of tumor cells with flaky coagulation necrosis were found. There were a large amount of lymphoid cells proliferation especially around the blood vessels and lymphocyte infiltration in blood vessel wall. The volume of some cells is medium to small, and other cells are medium to large. The nucleus is slightly irregular, and nucleolus enlargement and nuclear division were found (H&E staining, original magnification×200) (e); The diffuse expression of CD20-positive tumor cells ( immunohistochemical staining, original magnification×200) (f). The tumor cells with positive expression of Pax-5 (immunohistochemical staining, original magnification×200)(g). The positive EBV-encoded small RNA (EBER) was found (situ hybridization, original magnification×200) (h). Treatment regimen adjustment (i)

Fig. 2

The radiological, pathologic diagnosis and treatment of case 2. Brain contrast-enhanced MRI (a-d): A ring enhancement space-occupying lesion 4.7 × 4.6 × 3.4 cm in the right cerebellar hemisphere with an amygdala cerebelli herniation before treatment (In May, 2021) (a). Having a PR after 2 months treatment (In August, 2021) (b). Presenting a progressive disease after 6 months treatment (In December, 2021) (c). Achieving a CR after 13 months treatment (In August, 2022) and keeping a CR after 19 months treatment (In February, 2023) (d). Histological characteristics (e-h): Diffuse distribution of tumor cells with flaky coagulation necrosis was found. The volume of most cells is large. The nucleus is slightly irregular, and nucleolus enlargement and nuclear division were found (H&E staining, original magnification×200) (e). The diffuse expression of CD20-positive tumor cells (immunohistochemical staining, original magnification×200) (f). The tumor cells with positive expression of Pax-5 (immunohistochemical staining, original magnification×200) (g). The positive EBV-encoded small RNA (EBER) was found (situ hybridization, original magnification×200) (h). Treatment regimen adjustment (i)