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Measurable residual disease does not preclude prolonged progression-free survival in CLL treated with ibrutinib.

Publication ,  Journal Article
Wang, XV; Hanson, CA; Tschumper, RC; Lesnick, CE; Braggio, E; Paietta, EM; O'Brien, S; Barrientos, JC; Leis, JF; Zhang, CC; Coutre, SE ...
Published in: Blood
December 30, 2021

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.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

December 30, 2021

Volume

138

Issue

26

Start / End Page

2810 / 2827

Location

United States

Related Subject Headings

  • Vidarabine
  • Treatment Outcome
  • Rituximab
  • Protein Kinase Inhibitors
  • Progression-Free Survival
  • Prognosis
  • Piperidines
  • Neoplasm, Residual
  • Middle Aged
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
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Wang, X. V., Hanson, C. A., Tschumper, R. C., Lesnick, C. E., Braggio, E., Paietta, E. M., … Kay, N. E. (2021). Measurable residual disease does not preclude prolonged progression-free survival in CLL treated with ibrutinib. Blood, 138(26), 2810–2827. https://doi.org/10.1182/blood.2020010146
Wang, Xin Victoria, Curtis A. Hanson, Renee C. Tschumper, Connie E. Lesnick, Esteban Braggio, Elisabeth M. Paietta, Susan O’Brien, et al. “Measurable residual disease does not preclude prolonged progression-free survival in CLL treated with ibrutinib.Blood 138, no. 26 (December 30, 2021): 2810–27. https://doi.org/10.1182/blood.2020010146.
Wang XV, Hanson CA, Tschumper RC, Lesnick CE, Braggio E, Paietta EM, et al. Measurable residual disease does not preclude prolonged progression-free survival in CLL treated with ibrutinib. Blood. 2021 Dec 30;138(26):2810–27.
Wang, Xin Victoria, et al. “Measurable residual disease does not preclude prolonged progression-free survival in CLL treated with ibrutinib.Blood, vol. 138, no. 26, Dec. 2021, pp. 2810–27. Pubmed, doi:10.1182/blood.2020010146.
Wang XV, Hanson CA, Tschumper RC, Lesnick CE, Braggio E, Paietta EM, O’Brien S, Barrientos JC, Leis JF, Zhang CC, Coutre SE, Barr PM, Cashen AF, Mato AR, Singh AK, Mullane MP, Erba H, Stone R, Litzow MR, Tallman MS, Shanafelt TD, Kay NE. Measurable residual disease does not preclude prolonged progression-free survival in CLL treated with ibrutinib. Blood. 2021 Dec 30;138(26):2810–2827.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

December 30, 2021

Volume

138

Issue

26

Start / End Page

2810 / 2827

Location

United States

Related Subject Headings

  • Vidarabine
  • Treatment Outcome
  • Rituximab
  • Protein Kinase Inhibitors
  • Progression-Free Survival
  • Prognosis
  • Piperidines
  • Neoplasm, Residual
  • Middle Aged
  • Male