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

Diego Villa, Aixiang Jiang, Carlo Visco, Nicola Crosbie, Rory Mcculloch, Michael J. Buege, Anita Kumar, David a. Bond, Jonas Paludo, Matthew j. Maurer, Gita Thanarajasingam, Katharine l. Lewis, Chan y. Cheah, Joachim Baech, Tarec C. El-Galaly, Laveniya Kugathasan, David W. Scott, Alina S. Gerrie, David Lewis

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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 (2L) and subsequent lines of therapy. The purpose of this study was to evaluate factors predicting outcomes in patients with relapsed/refractory (R/R) MCL exclusively initiating second line (2L) Bruton's tyrosine kinase inhibitors (BTKi) 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: 160 in the main cohort and 200 in the validation cohort. Time to POD, Ki67 30%, and MIPI were associated with progression-free survival (PFS2) and overall survival (OS2) from the start of 2L BTKi. 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 MCL International Prognostic Index (MIPI) identifies 3 groups with distinct 2-year PFS2: 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 BTKi. 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.

Subjects:Lymphoid Neoplasia
Original languageEnglish
Pages (from-to)4576-4585
Number of pages10
JournalBlood advances
Issue number16
Publication statusPublished - 16 Aug 2023


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