Among patients with chronic lymphocytic leukemia (CLL) treated with indefinite ibrutinib, measurable residual disease (MRD) does not appear to predict the likelihood of prolonged progression-free survival (PFS), according to research published in Blood.

MRD has previously been established as a surrogate for PFS in CLL, particularly among patients treated with targeted therapy. Previously published data suggested that undetectable MRD after treatment is linked with both improved PFS and overall survival.

There is, however, little information published to date regarding whether MRD status predicts PFS among patients treated with ibrutinib, which may be taken for extended periods. For the present paper, researchers updated an MRD analysis from a previous phase 3 trial to determine whether MRD status predicts PFS among patients with CLL randomly assigned to receive indefinite ibrutinib. MRD negativity was defined as fewer than 1 CLL cell per 104 leukocytes.

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The phase 3 E1912 trial ( Identifier: NCT02048813) evaluated whether 6 cycles of ibrutinib and rituximab followed by indefinite ibrutinib or a combination of fludarabine, cyclophosphamide, and rituximab for cycles yields superior clinical outcomes among patients with CLL.

Among the 290 patients randomly assigned to the ibrutinib group, the mean age was 56.3 years, 66.9% of patients were male sex, and 62.4% had an Eastern Cooperative Oncology Group performance status of 0. Among patients tested for MRD status, 38 were MRD-negative while 252 were MRD-positive.

In the fludarabine group, MRD undetectability rates were 29.1%, 30.3%, 23.4%, and 8.6% at 3, 12, 24, and 36 months, respectively; in the ibrutinib group, the MRD undetectability rates at 12, 24, and 36 months were 7.9%, 4.2%, and 3.7%.

While MRD negativity predicted PFS in the fludarabine arm, no such finding was noted in the ibrutinib arm, except among patients with MRD levels of less than 10-1.

“In summary, the results of this large North American Intergroup phase 3 clinical trial provided valuable confirmatory as well as novel data on the utility of MRD analysis of [fludarabine, cyclophosphamide, and rituximab] vs [ibrutinib] treatment of de novo CLL,” the authors wrote.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Wang XV, Hanson CA, Tschumper RC, et al. Measurable residual disease does not preclude prolonged progression-free survival in CLL treated with ibrutinib. Blood. 2021;138(26):2810-2827. doi:10.1182/blood.2020010146