Immunochemotherapy with intensive consolidation for primary CNS lymphoma: a pilot study and prognostic assessment by diffusion-weighted MRI.
OBJECTIVE
We evaluated a novel therapy for primary central nervous system lymphoma (PCNSL) with induction immunochemotherapy with high-dose methotrexate, temozolomide, and rituximab (MT-R) followed by intensive consolidation with infusional etoposide and high-dose cytarabine (EA). In addition, we evaluated the prognostic value of the minimum apparent diffusion coefficient (ADC(min)) derived from diffusion-weighted MRI (DW-MRI) in patients treated with this regimen.


METHODS
Thirty-one patients (median age, 61 years; median Karnofsky performance score, 60) received induction with methotrexate every 14 days for 8 planned cycles. Rituximab was administered the first 6 cycles and temozolomide administered on odd-numbered cycles. Patients with responsive or stable central nervous system (CNS) disease received EA consolidation. Pretreatment DW-MRI was used to calculate the ADC(min) of contrast-enhancing lesions.


RESULTS
The complete response rate for MT-R induction was 52%. At a median follow-up of 79 months, the 2-year progression-free and overall survival were 45% and 58%, respectively. For patients receiving EA consolidation, the 2-year progression-free and overall survival were 78% and 93%, respectively. EA consolidation was also effective in an additional 3 patients who presented with synchronous CNS and systemic lymphoma. Tumor ADC(min) less than 384 × 10(-6) mm(2)/s was significantly associated with shorter progression-free and overall survival.


CONCLUSIONS
MT-R induction was effective and well tolerated. MT-R followed by EA consolidation yielded progression-free and overall survival outcomes comparable to regimens with chemotherapy followed by whole-brain radiotherapy consolidation but without evidence of neurotoxicity. Tumor ADC(min) derived from DW-MRI provided better prognostic information for PCNSL patients treated with the MTR-EA regimen than established clinical risk scores.
Division of Hematology/Oncology, University of California San Francisco, Box 1270, 505 Parnassus Avenue, San Francisco, CA 94143, USA. jamesr@medicine.ucsf.edu
Matthew J
MJ
Wieduwilt
Francisco
F
Valles
Samar
S
Issa
Caroline M
CM
Behler
James
J
Hwang
Michael
M
McDermott
Patrick
P
Treseler
Joan
J
O'Brien
Marc A
MA
Shuman
Soonmee
S
Cha
Lloyd E
LE
Damon
James L
JL
Rubenstein
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D060830:Consolidation Chemotherapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D038524:Diffusion Magnetic Resonance Imaging; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008223:Lymphoma / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D000069283:Rituximab; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome
D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D000069283:Rituximab; D005047:Etoposide; D003606:Dacarbazine; D000077204:Temozolomide; D008727:Methotrexate