Time to progression of disease and outcomes with second-line BTK inhibitors in relapsed/refractory mantle cell lymphoma Journal Article
| Authors: | Villa, D.; Jiang, A.; Visco, C.; Crosbie, N.; McCulloch, R.; Buege, M. J.; Kumar, A.; Bond, D. A.; Paludo, J.; Maurer, M. J.; Thanarajasingam, G.; Lewis, K. L.; Cheah, C. Y.; Baech, J.; El-Galaly, T. C.; Kugathasan, L.; Scott, D. W.; Gerrie, A. S.; Lewis, D. |
| Article Title: | Time to progression of disease and outcomes with second-line BTK inhibitors in relapsed/refractory mantle cell lymphoma |
| Abstract: | 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. © 2023 by The American Society of Hematology. |
| Keywords: | adult; cancer survival; aged; major clinical study; overall survival; prednisone; cisplatin; doxorubicin; cancer combination chemotherapy; cancer growth; dose response; treatment planning; cytarabine; rituximab; drug megadose; outcome assessment; ki 67 antigen; progression free survival; mantle cell lymphoma; cohort analysis; cyclophosphamide; dexamethasone; vincristine; drug effect; validation study; retrospective study; high risk patient; clinical evaluation; observational study; intermediate risk patient; low risk patient; cancer prognosis; ibrutinib; human; male; female; article; acalabrutinib; zanubrutinib; edralbrutinib |
| Journal Title: | Blood Advances |
| Volume: | 7 |
| Issue: | 16 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2023-08-22 |
| Start Page: | 4576 |
| End Page: | 4585 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2023009804 |
| PUBMED: | 37307169 |
| PROVIDER: | scopus |
| PMCID: | PMC10425680 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work