PATIENTS  CLL is not a one-size-fits-all illness.  Patients  respond very differently to the same anti-cancer drugs... Read more

SIGNATURE CLL Personalizing treatment by testing each patient’s own cancer cells against a wide range of candidate agents... Read more

  1. HEALTHCARE PROFESSIONALS  The gold standard in clinical validation has always been the prospective, randomized clinical trial... Read more

Personalized Cytometric Profiling Improves Survival in CLL

In the new age of personalized cancer treatment no method has undergone greater clinical trials scrutiny than the DiSC cytometric profiling assay in the setting of Chronic Lymphocytic Leukemia. 

A landmark study, published in the journal Leukemia, reports results of the second randomization of the LRF CLL4 prospective, randomized trial, involving CLL patients.1  The multi-institutional clinical trial compared patient outcomes when therapies were selected by physicians with or without results of personalized cytometric profiling using the DiSC Assay (a laboratory test).  

Improved Survival for Patients Receiving Assay-Directed Therapy versus Physician’s Choice Therapy

Relapsed CLL patients receiving “physician’s choice” chemotherapy (i.e. drugs chosen for them by their physicians, intuitively, without benefit of personalized cytometric profiling) were 2.5 times more likely to die within one year compared with patients whose treatments were based on DiSC Assay personalized cytometric profiling.  It is important to note that the design of this study made it impossible to show any survival advantage extending beyond one year as all patients were eligible to receive off-protocol treatments at first disease progression following the second randomization.  In spite of this, the one year survival advantage among cytometric profiling patients was unambiguous and statistically significant.  Remarkably, this is also the first clinical trial in history to show a survival advantage among any group of patients treated with chemotherapy alone in the setting of relapsed CLL.

For detailed discussion of this study: Click here

Improved Survival for Patients in Who Received Assay-positive Drugs

In the first randomization of LRF CLL4, 544 previously untreated CLL patients were tested in the DISC Assay prior to receiving chemotherapy.  Patients who received drugs prospectively identified by the DiSC Assay as “active” against their own CLL cells achieved a median overall survival of about 8 years.  Patients who received drugs which were identified by the DiSC Assay as having low or no activity against their own CLL cells survived a median of only 2 years.  Two conclusions are supported by these data: 1.) The DiSC Assay accurately predicts chemotherapy response in CLL. 2.) If possible, CLL patients should receive drugs identified as active in the DiSC Assay in preference to drugs found inactive.  

Solid Line = Patients treated with assay-active drugs

Dashed Line = Patients treated with intermediate activity drugs

Hashed Line = Patients treated with assay-low activity or no activity drugs

For additional explanation of this figure: Click here

The results of this study are supported by the results of numerous previous studies in which correlation between cytometric profiling results and patient outcomes have been uniformly positive.

Cytometric Profiling Circumvents Fludarabine Resistance in Previously-Treated and Previously-Untreated CLL Patients

Cytometric profiling via the DiSC Assay has also been extensively studied in the setting of previously untreated CLL.  Patients whose CLL cells were found resistant to fludarabine in the DiSC Assay (performed prior to treatment) had poor outcomes if, despite DiSC Assay results, these patients were treated with fludarabine (curve B, below).  Patients sensitive to fludarabine in the DiSC assay fared much better if actually treated with fludarabine (curve A, below).  Importantly, patients found resistant to fludarabine in the DiSC assay but who then received drugs other than fludarabine also had much better outcomes (curve C).  This strongly suggests that all CLL patients - both previously treated patients and previously untreated patients - should undergo DiSC Assay cytometric profiling prior to receiving either primary or salvage chemotherapy.2

For additional explanation of this figure: Click here

U.S. Healthcare Finance Administration Advisory Committee Finds Cytometric Profiling Clinically Useful in CLL

The Laboratory and Diagnostic Services Panel of the Medicare Advisory Committee, heard testimony from physicians, scientists, and cancer patients.  The expert panel also reviewed extensive scientific data.  The preponderance of data pertaining to CLL derived from studies published by Dr. Bosanquet and also by Dr. Weisenthal.  These studies specifically involved use of the DiSC Assay.  By unanimous vote, the eleven committee members promulgated the following position statement:

“In considering the presented evidence, the advisory panel believes that [cytometric profiling assays] demonstrate clinical utility for directing treatment of CLL...”

For further details of this formal HCFA review, Click here.

Cytometric profiling with the SignatuRx™ DiSC Assay is available for all CLL patients today.  Please call our laboratory for ordering information: (714) 596-2121.

  1. 1.Matutes E, Bosanquet AG, Wade R, et al, The use of individualized tumor response testing in treatment selection: second randomization results from the LRF CLL4 trial and the predictive value of the test at trial entry. Leukemia (2013) 27, 507–510; doi:10.1038/leu.2012.209.  Link to publication

  2. 2.Bosanquet AG, Johnson SA, Richards SM. Prognosis for fludarabine therapy of chronic lymphocytic leukaemia based on ex vivo drug response by DiSC assay. British Journal of Haematology. 1999; 106: 71-77.  Link to publication