H Ghesquieres1, M Chevrier2, M Laadhari3, O Chinot4, S Choquet5, C Moluçon-Chabrot6, P Beauchesne7, R Gressin8, F Morschhauser9, A Schmitt10, E Gyan11, K Hoang-Xuan12, E Nicolas-Virelizier13, N Cassoux14, V Touitou15, M Le Garff-Tavernier16, A Savignoni2, I Turbiez2, V Soumelis17, C Houillier12, C Soussain18. 1. Department of Hematology, Centre Hospitalier Lyon Sud, Université Claude Bernard Lyon 1, Pierre-Bénite; Department of Hematology, Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon. 2. Departments of Biostatistics, Aix Marseille University, AP-HM, Marseille. 3. Radiology, Institut Curie, Saint-Cloud, Aix Marseille University, AP-HM, Marseille. 4. Department of Neuro-Oncology, Hôpital de la Timone, Aix Marseille University, AP-HM, Marseille. 5. Department of Hematology, Groupe Hospitalier Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris. 6. Department of Hematology, CHU Clermont Ferrand, Clermond Ferrand. 7. Department of Neuro-Oncology, CHU Nancy, Nancy. 8. Department of Hematology, CHU La Tronche, Grenoble. 9. Department of Hematology, Centre Hospitalier Universitaire, Université de Lille, Lille. 10. Department of Hematology, Institut Bergonié, Bordeaux. 11. Department of Hematology and Cellular Therapy, CIC INSERM U1517, Centre Hospitalier Universitaire, Université de Tours, Tours. 12. Department of Neurology 2 Mazarin, Groupe Hospitalier Pitié-Salpêtrière, APHP, Sorbonne University, IHU, ICM, Paris. 13. Department of Hematology, Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon. 14. Department of Ophthalmology, Institut Curie - Site Paris, Paris. 15. Department of Ophthalmology, Hôpital Pitié Salpetrière, Université Pierre et Marie Curie, Paris. 16. Groupe Hospitalier Pitié-Salpétrière, Biological Hematology, Paris, France; Paris University Sorbonne UPMC, INSERM UMRS 1138, Paris. 17. Clinical Immunology Laboratory, Department of Biopathology, INSERM U932, Immunity and Cancer, Institut Curie, Paris. 18. Department of Hematology, Institut Curie, Saint-Cloud, France. Electronic address: carole.sousain@curie.fr.
Abstract
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 i.v. 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 12 28-day cycles of lenalidomide alone (10 mg/day, D1-21). The primary end point 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 assessable for response. The ORR at the end of induction was 35.6% (95% CI 21.9-51.2) in assessable 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 of PCNSL. CLINICAL TRIALS NUMBER: NCT01956695.
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 i.v. 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 12 28-day cycles of lenalidomide alone (10 mg/day, D1-21). The primary end point 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 assessable for response. The ORR at the end of induction was 35.6% (95% CI 21.9-51.2) in assessable 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 of PCNSL. CLINICAL TRIALS NUMBER: NCT01956695.
Authors: Matthew R Wilson; Toby A Eyre; Nicolas Martinez-Calle; Matthew Ahearne; Katrina E Parsons; Gavin Preston; Jahanzaib Khwaja; Jeremy Schofield; Johnathon Elliot; Almurtadha Mula Kh; Nimish Shah; Cheuk-Kie Cheung; Matthew A Timmins; Thomas Creasey; Kim Linton; Jeffery Smith; Christopher P Fox; Fiona Miall; Kate Cwynarski; Pamela McKay Journal: Blood Adv Date: 2020-08-11