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

Caroline Houillier (1) , S Dureau (2) , Luc Taillandier (3) , Roch Houot (4, 5) , O. Chinot (6) , Cécile Molucon-Chabrot (7) , Anna Schmitt (8) , Rémy Gressin (9) , Sylvain Choquet (10) , Gandhi Damaj (11, 12) , Frédéric Peyrade (13) , Julie Abraham (14) , V Delwail (15) , Emmanuel Gyan (16) , Laurence Sanhes (17) , Jerome Cornillon (18) , Reda Garidi , Alain Delmer (19) , Ahmad Al Jijakli , Pierre Morel (20, 21) , Agathe Waultier (22) , Jérôme Paillassa (23) , A Chauchet (24) , Thomas Gastinne (25) , Mouna Laadhari (2) , Anne-Sophie Plissonnier (2) , Loïc Feuvret (10) , Nathalie Cassoux (2) , Valerie Touitou (10) , Jean-Damien Ricard (26) , Khe Hoang-Xuan (1) , Carole Soussain (27, 2)

1 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
2 Institut Curie [Paris]
3 CHU Nancy - Centre Hospitalier Universitaire de Nancy
4 MOBIDIC - Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer
5 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
6 TIMONE - Hôpital de la Timone [CHU - APHM]
7 CHU Louise Michel [Clermont-Ferrand]
8 Institut Bergonié [Bordeaux]
9 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
10 CHU Pitié-Salpêtrière [AP-HP]
11 CHU Caen
12 CHU Amiens-Picardie
13 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
14 CHU Limoges
15 CIC 1402 - CIC Poitiers – Centre d'investigation clinique de Poitiers
16 CIC - Centre d’Investigation Clinique [Tours] CIC 1415
17 Centre Hospitalier Saint Jean de Perpignan
18 Institut de Cancérologie Lucien Neuwirth
19 Hôpital universitaire Robert Debré [Reims]
20 Centre Hospitalier de Lens
21 METRICS - Evaluation des technologies de santé et des pratiques médicales - ULR 2694
22 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
23 CHU Angers - Centre Hospitalier Universitaire d'Angers
24 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
25 CHU Nantes - Centre Hospitalier Universitaire de Nantes
26 Hôpital d'instruction des Armées Percy
27 U932 - Immunité et cancer

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.

Domaines: Sciences du Vivant [q-bio]

Caroline Houillier, S Dureau, Luc Taillandier, Roch Houot, O. Chinot, et al.. 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. Journal of Clinical Oncology, 2022, 40 (32), pp.3692-3698. ⟨10.1200/JCO.22.00491⟩. ⟨hal-03758013⟩