High-dose chemotherapy with autologous haematopoietic stem cell support for relapsed or refractory primary CNS lymphoma: a prospective multicentre trial by the German Cooperative PCNSL study group

Abstract

To investigate safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT) in relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL), we conducted a single-arm multicentre study for immunocompetent patients (<66 years) with PCNSL failing high-dose methotrexate)-based chemotherapy. Induction consisted of two courses of rituximab (375 mg/m), high-dose cytarabine (2 × 3 g/m) and thiotepa (40 mg/m) with collection of stem cells in between. Conditioning for HCT-ASCT consisted of rituximab 375 mg/m, carmustine 400 mg/m and thiotepa (4 × 5 mg/kg). Patients commenced HCT-ASCT irrespective of response after induction. Patients not achieving complete remission (CR) after HCT-ASCT received whole-brain radiotherapy. Primary end point was CR after HCT-ASCT. We enrolled 39 patients; median age and Karnofsky performance score are 57 years and 90%, respectively. About 28 patients had relapsed and 8 refractory disease. About 22 patients responded to induction and 32 patients commenced HCT-ASCT. About 22 patients (56.4%) achieved CR after HCT-ASCT. Respective 2-year progression-free survival (PFS) and overall survival (OS) rates were 46.0% (median PFS 12.4 months) and 56.4%; median OS not reached. We recorded four treatment-related deaths. Thiotepa-based HCT-ASCT is an effective treatment option in eligible patients with r/r PCNSL. Comparative studies are needed to further scrutinise the role of HCT-ASCT in the salvage setting.

Novel agents for primary central nervous system lymphoma: evidence and perspectives

“…This is still a heterogeneous patient population, and more investigations on relapse patterns and associated biomarkers should be conducted to further refine subgroups (eg, refractory and early relapse [eg, 6 months after last treatment]) to be selected for dedicated studies. Patients eligible for HCT-ASCT still have a reasonable chance (up to 50%) for long-term remissions, 15 and approaches including novel agents still have to show that they are able to improve that benchmark. Another approach worth mentioning is chimeric antigen receptor T-cell therapy, which has recently shown impressive results in r/r CD19-positive lymphoma.…”

“…10 There is no standard for second-line treatment, but several studies suggest that HD-MTX-free salvage regimens are effective, including HCT-ASCT. [11][12][13][14][15] However, many patients are not eligible for HCT-ASCT at relapse, and prognosis remains poor. PCNSL shares characteristics with systemic diffuse large B-cell lymphoma (DLBCL) but is a unique World Health Organization entity.…”

Thiotepa‐based conditioning versus total body irradiation as myeloablative conditioning prior to allogeneic stem cell transplantation for acute lymphoblastic leukemia: A matched‐pair analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…In the past decade, radiation‐free conditioning regimens have been consistently shown to confer a potent anti‐leukemia effect with concomitant avoidance of the major toxicities associated with TBI . In recent years, thiotepa, an alkylating agent initially introduced nearly six decades ago, has been gaining acceptance as effective therapy for primary and secondary central nervous system (CNS) lymphomas, in concert with additional agents . Indeed, thiotepa‐based radiation‐free conditioning has been used successfully in various hematologic malignancies .…”

Prolonged third complete remission after busulfan, thiotepa, and autologous stem cell transplant in a primary central nervous system lymphoma patient

“…The announced central nervous system (CNS) diffusion of busulfan is >80%, while that of cyclophosphamide is 20%‐30% . Thiotepa is a cytotoxic alkylating agent close to nitrogen mustards, passing the blood‐brain barrier with a ratio of 100% in the CSF, whose efficacy in myeloablative conditioning followed by ASCT in relapsing PNCSL has been well demonstrated since 1990 . The excellent CNS entrance of the thiothepa‐busulfan combination contrasts with that of agents in the BEAM‐ARAC high‐dose regimen, where CNS diffusion of BCNU is 15%‐70%, etoposide is <5%, and melphalan is 10% .…”