학술논문
Blood–Brain Barrier Disruption (BBBD)-Based Immunochemotherapy for Primary Central Nervous System Lymphoma (PCNSL), Early Results of a Phase II Study
Document Type
Report
Author
Kuitunen, Hanne K.; Rönkä, Aino L. K.; Sonkajärvi, Eila M.; Isokangas, Juha-Matti; Pyörälä, Marja; Palosaari, Kari A. A.; Jokimäki, Anna S.; Partanen, Anu E.; Littow, Harri J.; Vakkala, Merja A.; Jantunen, Esa J.; Huttunen, Mirja E.; Marin, Katja J.; Aromaa-Häyhä, Annikki M. K.; Auvinen, Päivi K.; Selander, Tuomas; Puhakka, Inka K.; Kuittinen, Outi M.
Source
Cancers. February 2023, Vol. 15 Issue 4
Subject
Language
English
ISSN
2072-6694
Abstract
Author(s): Hanne K. Kuitunen (corresponding author) [1,*]; Aino L. K. Rönkä [2]; Eila M. Sonkajärvi [3]; Juha-Matti Isokangas [4]; Marja Pyörälä [5]; Kari A. A. Palosaari [4]; Anna S. Jokimäki [...]
We present the results of a prospective trial of systemic chemoimmunotherapy for primary CNS lymphoma including the intra-arterial administration of methotrexate and carboplatin with blood–brain barrier disruption. The safety, response rates, and survival outcomes were favorable. Previous reports of the intra-arterial administration of therapy with blood–brain barrier disruption for this disease have also demonstrated safety and favorable outcomes, but there has been a slow uptake of this approach, partially out of concern that the technique may be difficult to implement across centers. Our data provide further prospective evidence that this approach can be implemented elsewhere with safety and confirm the effectiveness previously reported in a single institution study. These data motivate further study of this approach not only for PCNSL but also for other diseases that exist behind the blood–brain barrier. Primary central nervous system lymphoma is a rare but aggressive brain malignancy. It is associated with poor prognosis even with the current standard of care. The aim of this study was to evaluate the effect and tolerability of blood–brain barrier disruption treatment combined with high-dose treatment with autologous stem cell transplantation as consolidation on primary central nervous system lymphoma patients. We performed a prospective phase II study for 25 patients with previously untreated primary central nervous system lymphoma. The blood–brain barrier disruption treatment was initiated 3–4 weeks after the MATRix regimen using the previously optimized therapy protocol. Briefly, each chemotherapy cycle included two subsequent intra-arterial blood–brain barrier disruption treatments on days 1 and 2 via either one of the internal carotid arteries or vertebral arteries. Patients received the therapy in 3-week intervals. The treatment was continued for two more courses after achieving a maximal radiological response to the maximum of six courses. The complete treatment response was observed in 88.0% of the patients. At the median follow-up time of 30 months, median progression-free and overall survivals were not reached. The 2-year overall and progression-free survival rates were 67.1% and 70.3%, respectively. Blood–brain barrier disruption treatment is a promising option for primary central nervous system lymphoma with an acceptable toxicity profile.
We present the results of a prospective trial of systemic chemoimmunotherapy for primary CNS lymphoma including the intra-arterial administration of methotrexate and carboplatin with blood–brain barrier disruption. The safety, response rates, and survival outcomes were favorable. Previous reports of the intra-arterial administration of therapy with blood–brain barrier disruption for this disease have also demonstrated safety and favorable outcomes, but there has been a slow uptake of this approach, partially out of concern that the technique may be difficult to implement across centers. Our data provide further prospective evidence that this approach can be implemented elsewhere with safety and confirm the effectiveness previously reported in a single institution study. These data motivate further study of this approach not only for PCNSL but also for other diseases that exist behind the blood–brain barrier. Primary central nervous system lymphoma is a rare but aggressive brain malignancy. It is associated with poor prognosis even with the current standard of care. The aim of this study was to evaluate the effect and tolerability of blood–brain barrier disruption treatment combined with high-dose treatment with autologous stem cell transplantation as consolidation on primary central nervous system lymphoma patients. We performed a prospective phase II study for 25 patients with previously untreated primary central nervous system lymphoma. The blood–brain barrier disruption treatment was initiated 3–4 weeks after the MATRix regimen using the previously optimized therapy protocol. Briefly, each chemotherapy cycle included two subsequent intra-arterial blood–brain barrier disruption treatments on days 1 and 2 via either one of the internal carotid arteries or vertebral arteries. Patients received the therapy in 3-week intervals. The treatment was continued for two more courses after achieving a maximal radiological response to the maximum of six courses. The complete treatment response was observed in 88.0% of the patients. At the median follow-up time of 30 months, median progression-free and overall survivals were not reached. The 2-year overall and progression-free survival rates were 67.1% and 70.3%, respectively. Blood–brain barrier disruption treatment is a promising option for primary central nervous system lymphoma with an acceptable toxicity profile.