Time to progression of disease and outcomes with second-line BTK inhibitors in relapsed/refractory mantle cell lymphoma

• Published in: Blood advances 2023-08, Vol.7 (16), p.4576-4585
• Main Authors: Villa, Diego, Jiang, Aixiang, Visco, Carlo, Crosbie, Nicola, McCulloch, Rory, Buege, Michael J., Kumar, Anita, Bond, David A., Paludo, Jonas, Maurer, Matthew J., Thanarajasingam, Gita, Lewis, Katharine L., Cheah, Chan Y., Baech, Joachim, El-Galaly, Tarec C., Kugathasan, Laveniya, Scott, David W., Gerrie, Alina S., Lewis, David
• Format: Article
• Language: English
• Subjects: Lymphoid Neoplasia
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2023009804

•Time to POD after 1L rituximab-based chemotherapy is strongly associated with PFS and OS from the point of 2L BTKi initiation.•The 2L BTKi MIPI identifies patients expected to have limited disease control with 2L BTKis and who may benefit from other therapies. [Display omitted] Time to progression of disease (POD) after first-line (1L) therapy is prognostic in mantle cell lymphoma (MCL), although studies have included a broad range of 1L, second-line (2L), and subsequent lines of therapy. The purpose of this study was to evaluate the factors predicting outcomes in patients with relapsed/refractory (R/R) MCL exclusively initiating 2L Bruton’s tyrosine kinase inhibitors (BTKis) after 1L rituximab-containing therapy. Patients were accrued from 8 international centers (7 main, 1 validation cohort). Multivariable models evaluating the association between time to POD and clinical/pathologic factors were constructed and converted into nomograms and prognostic indexes predicting outcomes in this population. A total of 360 patients were included, including 160 in the main cohort and 200 in the validation cohort. Time to POD, Ki67 ≥ 30%, and MCL International Prognostic Index (MIPI) were associated with progression-free survival (PFS2) and overall survival (OS2) from the start of 2L BTKis. C-indexes were consistently ≥0.68 in both cohorts. Web/application-based calculators based on nomograms and prognostic indexes to estimate PFS2 and OS2 were constructed. The 2L BTKi MIPI identifies 3 groups with distinct 2-year PFS2, including high risk (14%), intermediate risk (50%), and low risk (64%). Time to POD, Ki67, and MIPI are associated with survival outcomes in patients with R/R MCL receiving 2L BTKis. Simple clinical models incorporating these variables may assist in planning for alternative therapies such as chimeric antigen receptor T-cell therapy, allogeneic stem cell transplantation, or novel agents with alternative mechanisms of action.