Measurable residual disease does not preclude prolonged progression-free survival in CLL treated with ibrutinib Journal Article
| Authors: | Wang, X. V.; Hanson, C. A.; Tschumper, R. C.; Lesnick, C. E.; Braggio, E.; Paietta, E. M.; O'Brien, S.; Barrientos, J. C.; Leis, J. F.; Zhang, C. C.; Coutre, S. E.; Barr, P. M.; Cashen, A. F.; Mato, A. R.; Singh, A. K.; Mullane, M. P.; Erba, H.; Stone, R.; Litzow, M. R.; Tallman, M. S.; Shanafelt, T. D.; Kay, N. E. |
| Article Title: | Measurable residual disease does not preclude prolonged progression-free survival in CLL treated with ibrutinib |
| Abstract: | E1912 was a randomized phase 3 trial comparing indefinite ibrutinib plus 6 cycles of rituximab (IR) to 6 cycles of fludarabine, cyclophosphamide, and rituximab (FCR) in untreated younger patients with CLL. We describe measurable residual disease (MRD) levels in E1912 over time and correlate them with clinical outcome. Undetectable MRD rates (<1 CLL cell per 104 leukocytes) were 29.1%, 30.3%, 23.4%, and 8.6% at 3, 12, 24, and 36 months for FCR, and significantly lower at 7.9%, 4.2%, and 3.7% at 12, 24, and 36 months for IR, respectively. Undetectable MRD at 3, 12, 24, and 36 months was associated with longer progression-free survival (PFS) in the FCR arm, with hazard ratios (MRD detectable/MRD undetectable) of 4.29 (95% confidence interval [CI], 1.89-9.71), 3.91 (95% CI, 1.39-11.03), 14.12 (95% CI, 1.78-111.73), and not estimable (no events among those with undetectable MRD), respectively. In the IR arm, patients with detectable MRD did not have significantly worse PFS compared with those in whom MRD was undetectable; however, PFS was longer in those with MRD levels <10−1 than in those with MRD levels above this threshold. Our observations provide additional support for the use of MRD as a surrogate end point for PFS in patients receiving FCR. In patients on indefinite ibrutinib-based therapy, PFS did not differ significantly by undetectable MRD status, whereas those with MRD <10−1 tended to have longer PFS, although continuation of ibrutinib would very likely be necessary to maintain treatment efficacy. © 2021 American Society of Hematology |
| Keywords: | adult; cancer survival; controlled study; aged; human cell; major clinical study; fludarabine; cancer combination chemotherapy; rituximab; progression free survival; multiple cycle treatment; randomized controlled trial; creatinine; cyclophosphamide; hemoglobin; creatinine blood level; fluorescence in situ hybridization; minimal residual disease; splenomegaly; hazard ratio; phase 3 clinical trial; beta 2 microglobulin; chronic lymphatic leukemia; cd5 antigen; leukocyte; lymphadenopathy; cd19 antigen; protein kinase zap 70; clinical outcome; coombs test; ibrutinib; human; male; female; article |
| Journal Title: | Blood |
| Volume: | 138 |
| Issue: | 26 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2021-12-30 |
| Start Page: | 2810 |
| End Page: | 2827 |
| Language: | English |
| DOI: | 10.1182/blood.2020010146 |
| PUBMED: | 34407545 |
| PROVIDER: | scopus |
| PMCID: | PMC8718628 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2022 -- Source: Scopus |
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