Phase Ib study with expansion of ibrutinib, lenalidomide, and rituximab in patients with relapsed/refractory central nervous system lymphoma Journal Article
| Authors: | Schaff, L. R.; Piotrowski, A. F.; Pentsova, E.; Gavrilovic, I. T.; Lin, A. D.; Kaley, T. J.; Wongchai, V.; Emadi-Paramkouhi, L.; Madzsar, J.; Quinn, L.; Gonzalez, A.; Breakey, L.; Tang, S. S.; Mendez, J. S.; Malani, R.; Nolan, C.; Hatzoglou, V.; Young, R. J.; DeAngelis, L. M.; Reiner, A. S.; Panageas, K. S.; Francis, J. H.; Mellinghoff, I. K.; Grommes, C. |
| Article Title: | Phase Ib study with expansion of ibrutinib, lenalidomide, and rituximab in patients with relapsed/refractory central nervous system lymphoma |
| Abstract: | Background Treatment options for recurrent/refractory central nervous system (CNS) lymphoma are limited but Bruton's tyrosine kinase inhibitor ibrutinib has shown promise. To increase efficacy and reduce resistance, ibrutinib was combined with lenalidomide in a preclinical study and rituximab ((RI)-I-2) in a phase Ib trial with expansion. Methods Ibrutinib 560 mg (dose level 1) or 840 mg (levels 2-4) was administered daily; lenalidomide was dosed on days 1-21 at 10 mg (level 1 + 2), 15 mg (level 3), or 20 mg (level 4) daily; rituximab 500 mg/m2 was administered every 28 days. Rituximab was given for 6 cycles, lenalidomide for 12 cycles, and ibrutinib ongoing. Results 25 patients were enrolled (3 each into dose levels 1-3; 6 into level 4; and 10 into the expansion cohort at level 4). The median age was 67 years (range 41-85) and the median Eastern Cooperative Oncology Group 1 (range 0-2). Patients had a median of 2 prior regimens (range 1-5). Common adverse events were thrombocytopenia, rash, and lymphopenia. No aspergillosis or grade 5 toxicities were observed. After 12.8 months of median follow-up, 20/25 (80%) showed a response with a median time to best response of 60 days (range, 25-615). Median progression-free survival (PFS) was 4.3 months (95% CI: 2.4-not reached) with a PFS12m of 37% (95% CI: 22%-63%). Median overall survival has not been reached. Patients with rash during treatment had improved PFS (HR: 0.17, 95% CI: 0.05-0.55, P-value = .003). Conclusions (RI)-I-2 was tolerated well with high response rates and a short time to best respond. Median PFS was limited but 1/3 of patients had durable responses >12 months. This trial was registered at www.clinicaltrials.gov (NCT03703167). |
| Keywords: | lenalidomide; primary cns lymphoma; tyrosine kinase; therapy; combination; central nervous system lymphoma; cns lymphoma; ibrutinib; indolent b-cell |
| Journal Title: | Neuro-Oncology |
| ISSN: | 1522-8517 |
| Publisher: | Oxford University Press |
| Publication status: | Online ahead of print |
| Date Published: | 2025-01-01 |
| Online Publication Date: | 2025-01-01 |
| Language: | English |
| ACCESSION: | WOS:001500235200001 |
| DOI: | 10.1093/neuonc/noaf104 |
| PROVIDER: | wos |
| Notes: | Article; Early Access -- Source: Wos |
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