Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma
Abstract Background Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare disorder with an increasing incidence over the past decades. High-level evidence has been reported for the MATRix regimen (high-dose methotrexate (HD-MTX), high-dose AraC (HD-AraC), thio...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-09723-w |
| _version_ | 1811273540493639680 |
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| author | Julia Wendler Christopher P. Fox Elke Valk Cora Steinheber Heidi Fricker Lisa K. Isbell Simone Neumaier Jessica Okosun Florian Scherer Gabriele Ihorst Kate Cwynarski Elisabeth Schorb Gerald Illerhaus |
| author_facet | Julia Wendler Christopher P. Fox Elke Valk Cora Steinheber Heidi Fricker Lisa K. Isbell Simone Neumaier Jessica Okosun Florian Scherer Gabriele Ihorst Kate Cwynarski Elisabeth Schorb Gerald Illerhaus |
| author_sort | Julia Wendler |
| collection | DOAJ |
| description | Abstract Background Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare disorder with an increasing incidence over the past decades. High-level evidence has been reported for the MATRix regimen (high-dose methotrexate (HD-MTX), high-dose AraC (HD-AraC), thiotepa and rituximab) followed by high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) supporting this approach to be considered a standard therapy in newly diagnosed PCNSL patients ≤ 70 years. However, early treatment-related toxicities (predominantly infectious complications), occurring in up to 28% per MATRix cycle, diminish its therapeutic success. Furthermore, sensitivity to first-line treatment is an independent prognostic factor for improved overall survival (OS) in PCNSL. Thus, patients achieving early partial remission (PR) after 2 cycles of MATRix might be over-treated with 4 cycles, in the context of consolidation HCT-ASCT. Methods This is an open-label, multicentre, randomized phase III trial with two parallel arms. 326 immunocompetent patients with newly diagnosed PCNSL will be recruited from 37 German, 1 Austrian and 12 UK sites. Additional IELSG (International Extranodal Lymphoma Study Group) sites are planned. The objective is to demonstrate superiority of a de-escalated and optimised remission induction treatment strategy, followed by HCT-ASCT. Randomization (1:1) will be performed after completion of all screening procedures. Patients in Arm A (control treatment) will receive 4 cycles of MATRix. Patients in Arm B (experimental treatment) will receive a pre-phase (R/HD-MTX), followed by 2 cycles of MATRix. Patients in both arms achieving PR or better will proceed to HCT-ASCT (BCNU, thiotepa). The primary endpoint of the study is event-free-survival (EFS), defined as time from randomization to premature end of treatment due to any reason, lymphoma progression or death whichever occurs first. Secondary endpoints include OS, progression free survival (PFS), toxicity, neurocognitive impairment and quality of life. Minimal follow-up is 24 months. Discussion Current treatment options for PCNSL in patients ≤ 70 years have improved remarkably over recent years. However, the potential efficacy benefits are offset by an increased incidence of short-term toxicities which can impact on treatment delivery and hence on survival outcomes. In patients ≤ 70 years with newly diagnosed PCNSL addressing the need to reduce treatment-related toxicity by de-escalating and optimising the induction phase of treatment, is a potentially attractive treatment strategy. Trial registration German clinical trials registry DRKS00022768 registered June 10th, 2021. |
| first_indexed | 2024-04-12T23:01:15Z |
| format | Article |
| id | doaj.art-7a730aa701ea4f188fc9c25f437b5b41 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T23:01:15Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-7a730aa701ea4f188fc9c25f437b5b412022-12-22T03:13:03ZengBMCBMC Cancer1471-24072022-09-012211910.1186/s12885-022-09723-wOptimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphomaJulia Wendler0Christopher P. Fox1Elke Valk2Cora Steinheber3Heidi Fricker4Lisa K. Isbell5Simone Neumaier6Jessica Okosun7Florian Scherer8Gabriele Ihorst9Kate Cwynarski10Elisabeth Schorb11Gerald Illerhaus12Clinic of Hematology, Oncology and Palliative CareRussell Centre for Clinical Haematology, Nottingham University Hospitals NHS TrustStuttgart Cancer Center - Tumorzentrum Eva Mayer-StihlStuttgart Cancer Center - Tumorzentrum Eva Mayer-StihlDepartment Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of FreiburgDepartment Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of FreiburgStuttgart Cancer Center - Tumorzentrum Eva Mayer-StihlCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of LondonDepartment Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of FreiburgClinical Trials Unit, Faculty of Medicine and Medical Center, University of FreiburgDepartment of Haematology, University College of London Hospitals, NHS Foundation TrustDepartment Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of FreiburgClinic of Hematology, Oncology and Palliative CareAbstract Background Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare disorder with an increasing incidence over the past decades. High-level evidence has been reported for the MATRix regimen (high-dose methotrexate (HD-MTX), high-dose AraC (HD-AraC), thiotepa and rituximab) followed by high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) supporting this approach to be considered a standard therapy in newly diagnosed PCNSL patients ≤ 70 years. However, early treatment-related toxicities (predominantly infectious complications), occurring in up to 28% per MATRix cycle, diminish its therapeutic success. Furthermore, sensitivity to first-line treatment is an independent prognostic factor for improved overall survival (OS) in PCNSL. Thus, patients achieving early partial remission (PR) after 2 cycles of MATRix might be over-treated with 4 cycles, in the context of consolidation HCT-ASCT. Methods This is an open-label, multicentre, randomized phase III trial with two parallel arms. 326 immunocompetent patients with newly diagnosed PCNSL will be recruited from 37 German, 1 Austrian and 12 UK sites. Additional IELSG (International Extranodal Lymphoma Study Group) sites are planned. The objective is to demonstrate superiority of a de-escalated and optimised remission induction treatment strategy, followed by HCT-ASCT. Randomization (1:1) will be performed after completion of all screening procedures. Patients in Arm A (control treatment) will receive 4 cycles of MATRix. Patients in Arm B (experimental treatment) will receive a pre-phase (R/HD-MTX), followed by 2 cycles of MATRix. Patients in both arms achieving PR or better will proceed to HCT-ASCT (BCNU, thiotepa). The primary endpoint of the study is event-free-survival (EFS), defined as time from randomization to premature end of treatment due to any reason, lymphoma progression or death whichever occurs first. Secondary endpoints include OS, progression free survival (PFS), toxicity, neurocognitive impairment and quality of life. Minimal follow-up is 24 months. Discussion Current treatment options for PCNSL in patients ≤ 70 years have improved remarkably over recent years. However, the potential efficacy benefits are offset by an increased incidence of short-term toxicities which can impact on treatment delivery and hence on survival outcomes. In patients ≤ 70 years with newly diagnosed PCNSL addressing the need to reduce treatment-related toxicity by de-escalating and optimising the induction phase of treatment, is a potentially attractive treatment strategy. Trial registration German clinical trials registry DRKS00022768 registered June 10th, 2021.https://doi.org/10.1186/s12885-022-09723-wPrimary central nervous system lymphoma (PCNSL)High-dose chemotherapy (HCT)Autologous stem cell transplantation (ASCT)ToxicityDe-escalation |
| spellingShingle | Julia Wendler Christopher P. Fox Elke Valk Cora Steinheber Heidi Fricker Lisa K. Isbell Simone Neumaier Jessica Okosun Florian Scherer Gabriele Ihorst Kate Cwynarski Elisabeth Schorb Gerald Illerhaus Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma BMC Cancer Primary central nervous system lymphoma (PCNSL) High-dose chemotherapy (HCT) Autologous stem cell transplantation (ASCT) Toxicity De-escalation |
| title | Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma |
| title_full | Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma |
| title_fullStr | Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma |
| title_full_unstemmed | Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma |
| title_short | Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma |
| title_sort | optimizing matrix as remission induction in pcnsl de escalated induction treatment in newly diagnosed primary cns lymphoma |
| topic | Primary central nervous system lymphoma (PCNSL) High-dose chemotherapy (HCT) Autologous stem cell transplantation (ASCT) Toxicity De-escalation |
| url | https://doi.org/10.1186/s12885-022-09723-w |
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