Lenalidomide in Combination with Intravenous Rituximab (REVRI) in Relapsed/Refractory Primary CNS Lymphoma or Primary Intraocular Lymphoma: a Multicenter Prospective “Proof of Concept” Phase II Study of the French Oculo-Cerebral Lymphoma (LOC) Network and the Lymphoma Study Association (LYSA)
Mené en France sur 50 patients atteints d'un lymphome primitif du système nerveux central ou d'un lymphome primitif intra-oculaire réfractaire ou récidivant, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité d'un traitement combinant lénalidomide et rituximab (durée médiane de suivi : 19,2 mois)
Background : Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal center B-cell (non-GCB) subtype. This study aimed to determine the efficacy of rituximab plus lenalidomide (R2) in DLBCL-PCNSL. Patients and Methods : Patients with refractory/relapsed (R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma (PVRL) were included in this prospective phase II study. The induction treatment consisted of eight 28-day cycles of R2 (rituximab 375/m2 IV, D1; lenalidomide 20 mg/day, D1-21 for cycle 1; and 25 mg/day, D1-21 for the subsequent cycles); in responding patients, the induction treatment was followed by a maintenance phase comprising twelve 28-day cycles of lenalidomide alone (10 mg/day, D1-21). The primary endpoint was the overall response rate (ORR) at the end of induction (P0=10%; P1=30%). Results : Fifty patients were included. Forty-five patients (PCNSL, N = 34; PVRL, N = 11) were evaluable for response. The ORR at the end of induction was 35.6% (95% CI, 21.9-51.2) in evaluable patients and 32.0% (95% CI, 21.9-51.2) in the intent-to-treat analysis, including 13 complete responses (CR)/unconfirmed CR (uCR; 29%) and 3 partial responses (PR; 7%). The best responses were 18 CR/uCR (40%) and 12 PR (27%) during the induction phase. The maintenance phase was started and completed by 18 and 5 patients, respectively. With a median follow-up of 19.2 months (range, 1.5-31), the median progression-free survival (PFS) and overall survival (OS) were 7.8 months (95% CI, 3.9-11.3) and 17.7 months (95% CI, 12.9 to not reached), respectively. No unexpected toxicity was observed. The peripheral baseline CD4/CD8 ratio impacted PFS (median PFS=9.5 months, [95% CI, 8.1-14.8] for CD4/CD8≥1.6; median PFS=2.8 months, [95% CI, 1.1-7.8] for CD4/CD8<1.6, P=0.03). Conclusions : The R2 regimen showed significant activity in R/R PCNSL and PVRL patients. These results support assessments of the efficacy of R2 combined with methotrexate-based chemotherapy as a first-line treatment for PCNSL https://academic.oup.com/annonc/advance-article-abstract/doi/10.1093/annonc/mdz032/5303990?redirectedFrom=PDF
Annals of Oncology 2019