In Leukemia, Minimal Disease Plus Clinical Response More Accurate Predictor of Survival

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MRD negativity with clinical response predicts progression-free survival in CLL.
MRD negativity with clinical response predicts progression-free survival in CLL.

SAN FRANCISCO—Minimal residual disease (MRD) negativity in peripheral blood after the end of treatment in combination with clinical response predicts progression-free survival (PFS) in patients with chronic lymphocytic leukemia (CLL) more accurately than clinical response alone, a combined analysis of two phase 3 studies (Abstract 23) concluded at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.

“These results support the use of MRD for response evaluation,” said Barbara Eichhorst, MD, of the Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital in Cologne, Germany. Analysis of the German CLL Study Group trials also found that the persistence of splenomegaly as a sole abnormality after treatment in MRD-negative patients had no corresponding negative influence on PFS.

Currently, the detection of MRD—recommended for clinical trials—is not formally included in the definition of CLL response assessment. To investigate its value in the context of clinical response, MRD status was explored in 555 patients with complete response (CR) and partial remission (PR) from two trials, one investigating fludarabine and cyclophosphamide with or without rituximab (FCR) and the other investigating FCR versus bendamustine and rituximab.

Among the 555 patients, 186 had MRD-negative CRs, 39 had MRD-positive CRs, 161 had MRD-negative PRs, and 169 had MRD-positive PRs. The median age of the patients was 61 years. At a median observation time of 45.4 months, median PFS was 68.9 months in the MRD-negative CR group, 44.4 months in the MRD-positive CR group, 61.7 months in the MRD-negative PR group, and 28.1 months in the MRD-positive PR group. For both PFS and overall survival the P-value was significant only for MRD-positive PRs (P=0.001) compared with MRD-negative CRs,

Multivariate Cox regression analysis of the effect of MRD and clinical response for PFS found that for positive versus negative MRD status, the hazard ratio was 3.487 (P<0.001); for PR versus CR clinical response, 1.420 (P=0.014); for the presence versus absence of deletion 17 p, 9.082 (P<0.001); and for unmutated versus mutated IgHV analysis, 2.582 (P<0.001).

Of the 161 patients with a MRD-negative PR, 25 had only lymphadenopathy; 18 had only bone marrow involvement; and 78 had only splenomegaly; 40 had more than one abnormality.

No significant difference in median PFS was observed between the patients with MRD-negative PRs with splenomegaly and those with MRD-negative CRs (72.0 versus 68.9 months, respectively; P=0.331).

More data are needed to provide the relevance of residual bone marrow involvement and lymphadenopathy in MRD-negative patients with PRs, Dr. Eichhorst concluded.


  1. Eichhorst, Barbara, MD, et al. "23 Value of Minimal Residual Disease (MRD) Negative Status at Response Evaluation in Chronic Lymphocytic Leukemia (CLL): Combined Analysis of Two Phase III Studies of the German CLL Study Group (GCLLSG)". ASH 2014. Oral Presentation. December 6, 2014.

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