Whether measurable residual disease (MRD) status is associated with progression-free survival (PFS) depends on the treatment regimen, according to research published in Blood.1

For patients with chronic lymphocytic leukemia (CLL) receiving indefinite ibrutinib plus 6 cycles of rituximab (IR), there was no significant difference in PFS between patients who achieved MRD negativity and those who did not. 

On the other hand, MRD negativity was associated with significantly prolonged PFS among CLL patients who received 6 cycles of fludarabine, cyclophosphamide, and rituximab (FCR).

Continue Reading

These results came from an analysis of data from the phase 3 E1912 trial (ClinicalTrials.gov Identifier: NCT02048813), which was designed to compare IR and FCR in a cohort of younger, previously untreated patients with CLL. Prior results from the trial showed superior PFS and overall survival with the IR regimen.2

For the current analysis, researchers measured MRD levels over time and correlated them with clinical outcomes. The analysis included 290 patients from the IR arm and 122 patients from the FCR arm.

In the FCR arm, the proportion of patients with undetectable MRD (< 1 CLL cell per 104 leukocytes) was 29.1% at 3 months, 30.3% at 12 months, 23.4% and 24 months, and 8.6% at 36 months. 

In the IR arm, the proportion of patients with undetectable MRD was significantly lower at the 3 time points measured — 7.9% at 12 months, 4.2% at 24 months, and 3.7% at 36 months (P <.001). 

In the FCR arm, undetectable MRD was associated with significantly better PFS at all time points:

  • 3 months (hazard ratio [HR], 4.29; 95% CI, 1.89-9.71; P <.001)
  • 12 months (HR, 3.91; 95% CI, 1.39-11.03; P =.005)
  • 24 months (HR, 14.12; 95% CI, 1.78-111.73; P <.001)
  • 36 months (HR not estimable; no events among those with undetectable MRD; P =.063).

In the IR arm, undetectable MRD was not associated with significantly better PFS at any time point (P =.14 at 12 months, P =.90 at 24 months, and P =.53 at 36 months).

However, at 12 months, PFS was significantly longer for patients with MRD levels of less than 10-1, compared with patients who had MRD levels above this threshold (HR, 2.03; 95% CI, 1.01-4.07; P =.041).

“Our data from the IR arm provides novel insights into the relationship of MRD with clinical outcome for ibrutinib-containing therapies that are continuously administered,” the researchers wrote. “As expected, MRD levels were highly predictive of outcome for the FCR-treated CLL patients, confirming prior reports.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


1. Wang V, Hanson CA, Tschumper R, et al. Measurable residual disease does not preclude prolonged progression-free survival in CLL treated with ibrutinib. Blood. Published online August 18, 2021. https://doi.org/10.1182/blood.2020010146

2. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381(5):432-443. doi:10.1056/NEJMoa181707