Sequenta's sequencing assay to measure residual disease is now being tested in two clinical trials for mantle cell lymphoma.
The sequencing-based assay, LymphoSight, uses proprietary multiplex PCR to amplify immune cell receptor rearrangements in T-cells and B-cells from blood and tissue.
Last year, the company presented data demonstrating that its assay could detect residual disease in cancer patients at levels undetectable by conventional methods such as flow cytometry, real-time PCR, and positron emission scans (CSN 12/14/2011).
Now, the assay will be run alongside two clinical trials to see if it can be used to predict which patients will relapse and also to monitor drug response over time.
The company will run the LymphoSight assay internally on the Illumina MiSeq platform, CEO Tom Willis told Clinical Sequencing News. The company is currently in the process of becoming CLIA certified, Willis added.
In both clinical trials, samples will be collected at multiple time points. The trials will run over several years, but Willis said that some results may be available before the trial ends.
In neither of the clinical trials is the primary purpose to demonstrate the effectiveness of the LymphoSight assay, and no clinical decisions will be made based on the test. Rather, the assay will be compared to flow cytometry and PET scanning techniques to see if it can help develop better prediction models that can then be tested in a separate clinical trial, explained Willis.
One trial is a 180-patient phase II clinical trial being run by SWOG (formerly Southwest Oncology Group) whose primary goal is to study the effectiveness of induction chemotherapy treatment before a stem cell transplant. SWOG includes more than 4,000 physician researchers at more than 500 institutions and is one of five cooperative groups that together comprise the National Cancer Institute's National Clinical Trials Network.
The trial is being coordinated by Steven Bernstein at the University of Rochester Medical Center.
In this trial, patient samples will be collected at 10 different time points during treatment and for up to three years after treatment. The LymphoSight assay will be run in conjunction with imaging, to compare the two techniques' ability to detect minimal residual disease, or MRD.
The assay will also be used in a 322-patient phase II trial to study the effect of two different drugs in induction and consolidation therapy that is being run by the Eastern Cooperative Oncology Group.
This trial will compare the LymphoSight assay to flow cytometry for detecting MRD and will assess the ability of using MRD as a prognostic marker. Patients with mantle cell lymphoma over 60 years of age will undergo MRD testing at eight different time points with both techniques during treatment and for up to three years afterwards.
The researchers will aim to develop sensitivity thresholds, and try to correlate the level of MRD with a relapse prediction. Previous studies have demonstrated that LymphoSight can detect B cells at levels as low as one cell per million, but it is unknown how that relates to prognosis, since current techniques are not as sensitive.
Techniques such as PET scans and flow cytometry can detect MRD down to about one cell in 10,000 and it has been demonstrated that MRD at this level is predictive of relapse.
However, patients with lower levels of disease also relapse, said Willis, but because these other techniques cannot detect disease at those levels, no one knows the level of MRD that is predictive of relapse. So the goal is to use the LymphoSight assay to set that bar.
Aside from establishing evidence for the ability of LymphoSight to provide prognostic value in cancer patients, Willis said that the trials will also help establish Sequenta as a clinical lab, as it aims to commercially launch its assay in 2013.
The company will be able to "evaluate the ability for us to handle clinical samples, gather the material necessary in a clinically standardized way," and deliver results in a clinically relevant timeframe, Willis said.
He did not disclose what Sequenta's turnaround time would be for the trials, but said that one of the main reasons the company chose to use the MiSeq, despite having developed the assay on the HiSeq, was because of its faster turnaround time.
The assay will ultimately be able to run on any sequencing platform, Willis said, adding that Sequenta continues to evaluate different sequencing technologies.