TY - JOUR
T1 - How we treat primary central nervous system lymphoma
AU - Calimeri, T.
AU - Steffanoni, S.
AU - Gagliardi, F.
AU - Chiara, A.
AU - Ferreri, A. J.M.
N1 - Funding Information:
TC: funding from Roche; other: Sandoz. AJMF: speaker fee from Adienne; research grants from Bristol-Myers Squibb, Beigene, Pharmacyclics, Hutchison Medipharma, Amgen, Genmab, ADC Therapeutics, Gilead, Novartis, and Pfizer; advisory boards from Gilead, Novartis, Juno, and PletixaPharm; inventor of patents on NGR-hTNF/RCHOP in relapsed or refractory PCNSL and SNGR-hTNF in brain tumors. All other authors have declared no conflicts of interest.
Funding Information:
We are indebted to our patients and their families for their generous commitment. We particularly thank hematologists, oncologists, neuroradiologists, pathologists, neurosurgeons, ophthalmologists, radiation oncologists, and psychologists at IRCCS San Raffaele Scientific Institute for the sustained clinical and scientific collaboration. We thank all the nurses for the clinical assistance and appreciate the excellent technical support of our study coordinator office. None declared. TC: funding from Roche; other: Sandoz. AJMF: speaker fee from Adienne; research grants from Bristol-Myers Squibb, Beigene, Pharmacyclics, Hutchison Medipharma, Amgen, Genmab, ADC Therapeutics, Gilead, Novartis, and Pfizer; advisory boards from Gilead, Novartis, Juno, and PletixaPharm; inventor of patents on NGR-hTNF/RCHOP in relapsed or refractory PCNSL and SNGR-hTNF in brain tumors. All other authors have declared no conflicts of interest.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/8
Y1 - 2021/8
N2 - Primary diffuse large B-cell (DLBCL) lymphoma of the central nervous system (CNS) (PCNSL) is a new lymphoma entity, recognized by the 2017 WHO classification of hematopoietic and lymphoid tumors. Unlike systemic DLBCL, the use of anthracycline-based chemotherapy combinations is associated with disappointing outcomes, due to low CNS bioavailability of related drugs. Therefore, international researchers investigated alternative strategies, mostly including drugs able to cross the blood–brain-barrier at low or high doses, with a progressive improvement in survival. Some effective chemotherapy combinations of high-dose methotrexate (HD-MTX) with alkylating agents and rituximab with or without cytarabine have been tested in international randomized trials and represent the induction treatment in everyday practice, with some variations among different geographical areas. In patients aged 70 years or younger, MATRix (HD-MTX/cytarabine/thiotepa/rituximab) chemotherapy followed by consolidative high-dose chemotherapy plus autologous stem cell transplantation or whole-brain irradiation has been associated with a significant improvement in overall survival. Other treatment options, such as non-myeloablative high-dose chemotherapy, oral drug maintenance, and some targeted drugs like ibrutinib or lenalidomide, are being tested in high-level international trials. These steps toward further effective treatments are motivated by an incessant search for less neurotoxic options. Thanks to international cooperation, we can affirm that PCNSL is a potentially curable tumor, especially in young patients. However, several questions remain unanswered: the optimal treatment for elderly patients as well as the management of intraocular and meningeal disease require further scientific efforts. Beside treatments, advances on molecular and radiological diagnostic tools will increase our knowledge of this disease, allowing the possibility to anticipate diagnosis and to better categorize patients' responses. This article analyzes the available literature in this setting and provides evidence-based recommendations for the management of PCNSL patients.
AB - Primary diffuse large B-cell (DLBCL) lymphoma of the central nervous system (CNS) (PCNSL) is a new lymphoma entity, recognized by the 2017 WHO classification of hematopoietic and lymphoid tumors. Unlike systemic DLBCL, the use of anthracycline-based chemotherapy combinations is associated with disappointing outcomes, due to low CNS bioavailability of related drugs. Therefore, international researchers investigated alternative strategies, mostly including drugs able to cross the blood–brain-barrier at low or high doses, with a progressive improvement in survival. Some effective chemotherapy combinations of high-dose methotrexate (HD-MTX) with alkylating agents and rituximab with or without cytarabine have been tested in international randomized trials and represent the induction treatment in everyday practice, with some variations among different geographical areas. In patients aged 70 years or younger, MATRix (HD-MTX/cytarabine/thiotepa/rituximab) chemotherapy followed by consolidative high-dose chemotherapy plus autologous stem cell transplantation or whole-brain irradiation has been associated with a significant improvement in overall survival. Other treatment options, such as non-myeloablative high-dose chemotherapy, oral drug maintenance, and some targeted drugs like ibrutinib or lenalidomide, are being tested in high-level international trials. These steps toward further effective treatments are motivated by an incessant search for less neurotoxic options. Thanks to international cooperation, we can affirm that PCNSL is a potentially curable tumor, especially in young patients. However, several questions remain unanswered: the optimal treatment for elderly patients as well as the management of intraocular and meningeal disease require further scientific efforts. Beside treatments, advances on molecular and radiological diagnostic tools will increase our knowledge of this disease, allowing the possibility to anticipate diagnosis and to better categorize patients' responses. This article analyzes the available literature in this setting and provides evidence-based recommendations for the management of PCNSL patients.
KW - high-dose methotrexate
KW - ibrutinib
KW - lenalidomide
KW - primary CNS lymphoma
KW - primary vitreoretinal lymphoma
UR - http://www.scopus.com/inward/record.url?scp=85117623534&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85117623534&partnerID=8YFLogxK
U2 - 10.1016/j.esmoop.2021.100213
DO - 10.1016/j.esmoop.2021.100213
M3 - Review article
C2 - 34271311
AN - SCOPUS:85117623534
SN - 2059-7029
VL - 6
JO - ESMO Open
JF - ESMO Open
IS - 4
M1 - 100213
ER -