Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life—experience of the French Network

Schenone, Laurence; Houillier, Caroline; Tanguy, Marie Laure; Choquet, Sylvain; Agbetiafa, Kossi; Ghesquières, Hervé; Damaj, Gandhi; Schmitt, Anna; Bouabdallah, Krimo; Ahle, Guido; Gressin, Rémy; Cornillon, Jérôme; Houot, Roch; Marolleau, Jean‐Pierre; Fornecker, Luc‐Matthieu; Chinot, Olivier; Peyrade, Fréd́eric; Bouabdallah, Réda; Moluçon‐Chabrot, Cécile; Gyan, Emmanuel; Chauchet, Adrien; Casasnovas, Olivier; Obéric, Lucie; Delwail, Vincent; Abraham, Julie; Roland, Virginie; Waultier-Rascalou, Agathe; Willems, Lise; Morschhauser, Franck; Fabbro, Michel; Ursu, Rénata; Thiéblemont, Catherine; Jardin, Fabrice; Tempescul, Adrian; Denis, Maxime; Nichelli, Lucia; Garff‐Tavernier, Magali Le; Plessier, Aurélie; Bourget, Philippe; Bonmati, Caroline; Wantz-Mézières, Sophie; Giordan, Quentin; Dorvaux, Véronique; Charron, Cyril; Jabeur, Waliyde; Hoang-Xuân, Khê; Taillandier, Luc; Soussain, Carole

doi:10.1038/s41409-022-01648-z

Cited by 19 publications

(19 citation statements)

References 37 publications

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“…Extended follow-up confirmed the lower incidence of relapse after ASCT, which was not observed in the IELSG32 study using thiotepa-BCNU-ASCT. 2 Retrospective studies 4,5 have showed a higher relapse risk after thiotepa-BCNU-ASCT than after TBC-ASCT. The incidence of TBC-ASCT-related deaths in patients with nonprogressive disease was 7%, as previously observed.…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study

Houillier

Dureau

Taillandier

et al. 2022

JCO

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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported the results of a randomized phase II study in patients with newly diagnosed primary CNS lymphoma (age 18-60 years). Patients were treated with high-dose methotrexate-based induction chemotherapy followed by whole-brain radiotherapy (WBRT) or high-dose chemotherapy (thiotepa-busulfan-cyclophosphamide) with autologous stem-cell transplantation (ASCT). The median follow-up was 33 months. In this report, we provide long-term data (median follow-up, 8 years) regarding the outcomes and toxicities. Fifty-three and 44 patients received induction chemotherapy followed by WBRT or ASCT, respectively. Their 8-year event-free survival from random assignment was 67% and 39% in the ASCT and WBRT arms, respectively ( P = .03), with a significantly lower risk of relapse after ASCT (hazard ratio = 0.13, P < .001). One third of patients who relapsed after WBRT were alive after salvage treatment. Five and four patients died of ASCT and WBRT-related toxicities, respectively. The 8-year overall survival was 69% and 65% in the ASCT and WBRT arms, respectively (not significant). Balance (52% v 10%, P ≤ 0.001) and neurocognition (64% v 13%, P < .001) significantly deteriorated after WBRT compared with ASCT during the follow-up. This study shows that 40 Gy WBRT should be avoided in first-line treatment because of its neurotoxicity and suboptimal efficacy in reducing relapses while ASCT appears to be highly efficient in preventing relapses.

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Section: Discussionmentioning

confidence: 99%

Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study

Houillier

Dureau

Taillandier

et al. 2022

JCO

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“…After induction treatment, 71.2% of patients received HD-CT with ASCT. HD-CT was an association of rituximab-busulfan-thiotepa (thiotepa-busulfan seemed to confer the highest response rate versus the BEAM regimen in past study [70 ▪▪ ]). Median PFS and median OS was 41.1 months and 41.1 months respectively, CR occurred for 44.2% of patients.…”

Section: How To Treat Newly-diagnosed Elderly Patients With Primary C...mentioning

confidence: 99%

Primary central nervous system lymphoma (PCNSL) in older patients

Bertucci

Harlay

Chinot

et al. 2023

Current Opinion in Oncology

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Introduction Primary central nervous system lymphoma (PCNSL) is a rare, chemo and radio-sensitive tumor limited to the central nervous system. The incidence of PCSNL increases notably in the elderly population which represented approximately half of the patients. The limit of ‘elderly’ population remained debated and nonuniform, including 60 years as a cutoff for brain radiotherapy, 65 years for autologous stem-cell transplantation, and 70 years for the last clinical trials. Current therapeutic options include first line treatment based on high-dose methotrexate based polychemotherapy, consolidation chemotherapy, and adapted autologous stem cell transplantation for highly selected patients. At relapse, single agent targeted therapies or salvage chemotherapy followed by intensive consolidation are promising therapeutic options. Nevertheless, improving management of elderly patients is an urgent medical need that currently remains unresolved. Objective We will focus on elderly patients with PCNSL and their specificities including clinical presentations, available therapeutic options and adaptations to be made. Conclusion To improve survival, it will be necessary to personalized and adapt the treatments, to each patient and his comorbidities, to increase their effectiveness and limit their toxicity in this frail population. Finally, inclusion of these patients in clinical trials is one of the major challenges to significantly change PCNSL elderly patient prognosis.

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“…Among IC, the BEAM regimen yielded to inferior outcome in two retrospective studies, compared to thiotepa-based IC [35 ▪ ,36]. Thiotepa-busulfan-cyclophosphamide resulted in a lower incidence of relapse but with a higher treatment-related mortality than thiotepa-BCNU regimen [35 ▪ ,36,37]. Thiotepa-busulfan showed promising results in terms of efficacy and toxicity [38].…”

Section: Consolidation Treatmentmentioning

confidence: 99%

First line treatments in primary central nervous system lymphomas in young patients

Schenone

Alcantara

Houillier

et al. 2023

Current Opinion in Oncology

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Purpose of review The aim of this review is to provide an update on current first-line treatments as well as on-going studies in immunocompetent patients with primary central nervous system lymphomas. Recent findings High-dose methotrexate (HD-MTX)-based polychemotherapy is widely used in induction treatment (IT). Among HD-MTX-based regimens, the best association is not yet defined. IT should be followed by a consolidation or a maintenance according to patient's age and performance status. Thiotepa-based intensive chemotherapy (IC) followed by autologous stem cell transplantation (ASCT) has improved survival in eligible patients compared to a nonmyeloablative consolidation. Because of the high risk of neurotoxicity, conventional whole brain radiotherapy (WBRT; 36–40 Gy) has been abandoned. Reduced-WBRT (23.4 Gy) is an alternative option in patients under 60 years-old in complete response after IT. Its safety remains to be demonstrated in elderly patients. The benefit of maintenance strategies to reduce the risk of relapse is being assessed in several studies in patients beyond 70 years-old. Summary HD-MTX-based polychemotherapy remains the corner stone of the IT, but the best regimen is not yet defined. Clinical trials assessing new IT regimens are ongoing. Intensive consolidation with IC + ASCT benefits patients up to 70 years-old. Predictive factors are under investigation to better define therapeutic response and guide treatment adjustment.

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Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life—experience of the French Network

Cited by 19 publications

References 37 publications

Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study

Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study

Primary central nervous system lymphoma (PCNSL) in older patients

First line treatments in primary central nervous system lymphomas in young patients

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