High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary diffuse large B-cell CNS lymphoma (MARTA): a single-arm, phase 2 trial
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High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary diffuse large B-cell CNS lymphoma (MARTA): a single-arm, phase 2 trial. / Schorb, Elisabeth; Isbell, Lisa Kristina; Kerkhoff, Andrea; Mathas, Stephan; Braulke, Friederike; Egerer, Gerlinde; Röth, Alexander; Schliffke, Simon; Borchmann, Peter; Brunnberg, Uta; Kroschinsky, Frank; Möhle, Robert; Rank, Andreas; Wellnitz, Dominique; Kasenda, Benjamin; Pospiech, Lisa; Wendler, Julia; Scherer, Florian; Deckert, Martina; Henkes, Elina; von Gottberg, Philipp; Gmehlin, Dennis; Backenstraß, Matthias; Jensch, Antje; Burger-Martin, Elvira; Grishina, Olga; Fricker, Heidi; Malenica, Natalie; Orbán, András; Duyster, Justus; Ihorst, Gabriele; Finke, Juergen; Illerhaus, Gerald.
in: LANCET HAEMATOL, Jahrgang 11, Nr. 3, 03.2024, S. e196-e205.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary diffuse large B-cell CNS lymphoma (MARTA): a single-arm, phase 2 trial
AU - Schorb, Elisabeth
AU - Isbell, Lisa Kristina
AU - Kerkhoff, Andrea
AU - Mathas, Stephan
AU - Braulke, Friederike
AU - Egerer, Gerlinde
AU - Röth, Alexander
AU - Schliffke, Simon
AU - Borchmann, Peter
AU - Brunnberg, Uta
AU - Kroschinsky, Frank
AU - Möhle, Robert
AU - Rank, Andreas
AU - Wellnitz, Dominique
AU - Kasenda, Benjamin
AU - Pospiech, Lisa
AU - Wendler, Julia
AU - Scherer, Florian
AU - Deckert, Martina
AU - Henkes, Elina
AU - von Gottberg, Philipp
AU - Gmehlin, Dennis
AU - Backenstraß, Matthias
AU - Jensch, Antje
AU - Burger-Martin, Elvira
AU - Grishina, Olga
AU - Fricker, Heidi
AU - Malenica, Natalie
AU - Orbán, András
AU - Duyster, Justus
AU - Ihorst, Gabriele
AU - Finke, Juergen
AU - Illerhaus, Gerald
N1 - Copyright © 2024 Elsevier Ltd. All rights reserved.
PY - 2024/3
Y1 - 2024/3
N2 - BACKGROUND: Available treatments for older patients with primary diffuse large B-cell CNS lymphoma (PCNSL) offer progression-free survival of up to 16 months. We aimed to investigate an intensified treatment of high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT) in older patients with PCNSL.METHODS: MARTA was a prospective, single-arm, phase 2 study done at 15 research hospitals in Germany. Patients aged 65 years or older with newly diagnosed, untreated PCNSL were enrolled if they had an Eastern Cooperative Oncology Group performance status of 0-2 and were fit for high-dose chemotherapy and autologous HSCT. Induction treatment consisted of two 21-day cycles of high-dose intravenous methotrexate 3·5 g/m2 (day 1), intravenous cytarabine 2 g/m2 twice daily (days 2 and 3), and intravenous rituximab 375 mg/m2 (days 0 and 4) followed by high-dose chemotherapy with intravenous rituximab 375 mg/m2 (day -8), intravenous busulfan 3·2 mg/kg (days -7 and -6), and intravenous thiotepa 5 mg/kg (days -5 and -4) plus autologous HSCT. The primary endpoint was progression-free survival at 12 months in all patients who met eligibility criteria and started treatment. The study was registered with the German clinical trial registry, DRKS00011932, and recruitment is complete.FINDINGS: Between Nov 28, 2017, and Sept 16, 2020, 54 patients started induction treatment and 51 were included in the full analysis set. Median age was 71 years (IQR 68-75); 27 (53%) patients were female and 24 (47%) were male. At a median follow-up of 23·0 months (IQR 16·8-37·4), 23 (45%) of 51 patients progressed, relapsed, or died. 12-month progression-free survival was 58·8% (80% CI 48·9-68·2; 95% CI 44·1-70·9). During induction treatment, the most common grade 3-5 toxicities were thrombocytopenia and leukopenia (each in 52 [96%] of 54 patients). During high-dose chemotherapy and autologous HSCT, the most common grade 3-5 toxicity was leukopenia (37 [100%] of 37 patients). Treatment-related deaths were reported in three (6%) of 54 patients, all due to infectious complications.INTERPRETATION: Although the primary efficacy threshold was not met, short induction followed by high-dose chemotherapy and autologous HSCT is active in selected older patients with PCNSL and could serve as a benchmark for comparative trials.FUNDING: Else Kröner-Fresenius Foundation, Riemser Pharma, and Medical Center-University of Freiburg.
AB - BACKGROUND: Available treatments for older patients with primary diffuse large B-cell CNS lymphoma (PCNSL) offer progression-free survival of up to 16 months. We aimed to investigate an intensified treatment of high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT) in older patients with PCNSL.METHODS: MARTA was a prospective, single-arm, phase 2 study done at 15 research hospitals in Germany. Patients aged 65 years or older with newly diagnosed, untreated PCNSL were enrolled if they had an Eastern Cooperative Oncology Group performance status of 0-2 and were fit for high-dose chemotherapy and autologous HSCT. Induction treatment consisted of two 21-day cycles of high-dose intravenous methotrexate 3·5 g/m2 (day 1), intravenous cytarabine 2 g/m2 twice daily (days 2 and 3), and intravenous rituximab 375 mg/m2 (days 0 and 4) followed by high-dose chemotherapy with intravenous rituximab 375 mg/m2 (day -8), intravenous busulfan 3·2 mg/kg (days -7 and -6), and intravenous thiotepa 5 mg/kg (days -5 and -4) plus autologous HSCT. The primary endpoint was progression-free survival at 12 months in all patients who met eligibility criteria and started treatment. The study was registered with the German clinical trial registry, DRKS00011932, and recruitment is complete.FINDINGS: Between Nov 28, 2017, and Sept 16, 2020, 54 patients started induction treatment and 51 were included in the full analysis set. Median age was 71 years (IQR 68-75); 27 (53%) patients were female and 24 (47%) were male. At a median follow-up of 23·0 months (IQR 16·8-37·4), 23 (45%) of 51 patients progressed, relapsed, or died. 12-month progression-free survival was 58·8% (80% CI 48·9-68·2; 95% CI 44·1-70·9). During induction treatment, the most common grade 3-5 toxicities were thrombocytopenia and leukopenia (each in 52 [96%] of 54 patients). During high-dose chemotherapy and autologous HSCT, the most common grade 3-5 toxicity was leukopenia (37 [100%] of 37 patients). Treatment-related deaths were reported in three (6%) of 54 patients, all due to infectious complications.INTERPRETATION: Although the primary efficacy threshold was not met, short induction followed by high-dose chemotherapy and autologous HSCT is active in selected older patients with PCNSL and could serve as a benchmark for comparative trials.FUNDING: Else Kröner-Fresenius Foundation, Riemser Pharma, and Medical Center-University of Freiburg.
KW - Humans
KW - Female
KW - Male
KW - Aged
KW - Prospective Studies
KW - Rituximab
KW - Lymphoma, Large B-Cell, Diffuse/drug therapy
KW - Hematopoietic Stem Cell Transplantation
KW - Leukopenia
U2 - 10.1016/S2352-3026(23)00371-X
DO - 10.1016/S2352-3026(23)00371-X
M3 - SCORING: Journal article
C2 - 38301670
VL - 11
SP - e196-e205
JO - LANCET HAEMATOL
JF - LANCET HAEMATOL
SN - 2352-3026
IS - 3
ER -
