CHemoImmunotherapy With Early Central Nervous System (CNS) Prophylaxis

Summary

The purpose is to test whether early central nervous system (CNS) prophylaxis given at the beginning of therapy for young high risk diffuse large B-cell lymphoma (DLBCL) patients is feasible and could reduce the risk of CNS relapses. Early CNS prophylaxis with two courses high dose methotrexate (HD-MTX) in combination with rituximab-cyclophosphamide-doxorubicin-vincristine-prednison (R-CHOP) is followed by four courses of R-CHOP14 and etoposide (E) and one course of HD-Ara-C. In addition the patients will receive three courses of liposomal cytarabine intrathecally. The results will be compared to a recent Nordic CRY-04 study. Shifting of CNS prophylaxis to the beginning of the therapy offers a potential to overcome the subclinical disease and thus reduce the risk of early clinical CNS recurrence. As flow cytometry (FCM) can improve the sensitivity for detecting occult leptomeningeal disease over cytology , FCM from cerebrospinal fluid will be incorporated into the staging procedures.

Timeline

Start

2011-03

Primary completion

2018-11

Completion

2019-12-31

Outcome

Met primary endpoint

paper Treatment reduced the risk of progression compared with our previous trial PMID 32380536 ↗

paper (hazard ratio, 0.49; 95% CI, 0.31-0.77; P = .002) PMID 32380536 ↗

Publications

• Mayerhoefer ME, Kienzle A, Woo S, Vargas HA. Update on Liquid Biopsy. Radiology. 2025 Jun;315(3):e241030. doi: 10.1148/radiol.241030.
• Arffman M, Meriranta L, Autio M, Holte H, Jorgensen J, Brown P, Jyrkkio S, Jerkeman M, Drott K, Fluge O, Bjorkholm M, Karjalainen-Lindsberg ML, Beiske K, Pedersen MO, Leivonen SK, Leppa S. Inflammatory and subtype-dependent serum protein signatures predict survival beyond the ctDNA in aggressive B cell lymphomas. Med. 2024 Jun 14;5(6):583-602.e5. doi: 10.1016/j.medj.2024.03.007. Epub 2024 Apr 4.
• Vajavaara H, Leivonen SK, Jorgensen J, Holte H, Leppa S. Low lymphocyte-to-monocyte ratio predicts poor outcome in high-risk aggressive large B-cell lymphoma. EJHaem. 2022 Jun 23;3(3):681-687. doi: 10.1002/jha2.409. eCollection 2022 Aug.
• Leppa S, Jorgensen J, Tierens A, Meriranta L, Ostlie I, de Nully Brown P, Fagerli UM, Larsen TS, Mannisto S, Munksgaard L, Maisenholder M, Vasala K, Meyer P, Jerkeman M, Bjorkholm M, Fluge O, Jyrkkio S, Liestol K, Ralfkiaer E, Spetalen S, Beiske K, Karjalainen-Lindsberg ML, Holte H. Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis. Blood Adv. 2020 May 12;4(9):1906-1915. doi: 10.1182/bloodadvances.2020001518.
• Autio M, Leivonen SK, Bruck O, Mustjoki S, Meszaros Jorgensen J, Karjalainen-Lindsberg ML, Beiske K, Holte H, Pellinen T, Leppa S. Immune cell constitution in the tumor microenvironment predicts the outcome in diffuse large B-cell lymphoma. Haematologica. 2021 Mar 1;106(3):718-729. doi: 10.3324/haematol.2019.243626.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Cytarabine	Small molecule	50 mg	Intrathecal

Indications

No indication recorded.