Real-World MRD Responses Observed With NGS in Acute Lymphoblastic Leukemia and Other Lymphoid Cancers

May 27, 2020

"The ability for NGS to assess response across a continuum of relevant MRD threshold levels is an important consideration for applying MRD testing in clinical practice."

DNA sequencing in a high proportion of patients with acute lymphoblastic leukemia (ALL) and multiple myeloma (MM) can be identified with a Clonality (ID) test which is carried out by a next-generation sequencing (NGS)-minimal residual disease (MRD) assay, as shown in a real-world retrospective analysis presented at the 2020 National Comprehensive Cancer Network (NCCN) Virtual Annual Meeting.

The study was conducted to address the need for better ways to measure response in patients since there have been advances in the care landscape of lymphoid cancers. The NCCN guidelines for lymphoid cancers recommend MRD assessment for patients with ALL, MM, and chronic lymphocytic leukemia. Although, most clinical trials involving these malignancies report MRD findings, information about MRD testing patterns and response levels from patients in the real-world setting are not abundant.

The NGS-MRD assay, cloneSEQ, developed by Adaptive Biotechnologies identifies, classifies, and tracks disease-associated DNA sequence rearrangement or clonotypes. Theses rearrangements include immunoglobulin (Ig) IgH (V-J), IgH (D-J), IgK, and IgL receptor gene sequences as well as translocated BCL1/IGH (J) and BCL2/IGH (J), and dominant T-cell receptor (TCR) β and TCRγ sequences.

Patients were selected from a de-identified internal dataset of results from the cloneSEQ obtained from January 2018 to October 2019. A baseline (ID) clonality assessment revealed patients who had detectable DNA sequences, and these were the patients who were included in the MRD assessment. The clonality assessment performed at baseline also evaluated patient demographics and the depth of MRD response.

The overall study population consisted of 2,138 patients with ALL (n = 803) or MM (n = 1,541). Based on the clonality test results, a total of 206 patient samples were polyclonal, 2,138 were calibrated, and the overall calibration rate was 91.2%. In the ALL arm versus the MM arm, there were 72 versus 134 polyclonal samples and 731 versus 1,407 calibrated samples. The median age was 65 years in the MM population and 25 years in the ALL group. Most patients were male 1,223 compared to the female population of 850 patients.

According to the response analysis, a higher percentage of MRD response was observed in patients with ALL (78.4%) compared with those who had MM (47.5%). In addition, deeper MRD responses were detected in 68.7% of patients in the ALL subgroup and 30.6% of patients in the MM subgroup. Specifically, MRD levels in patients with deeper responses were below 10-6. At all other MRD levels, the MM group showed deeper responses. MRD response in the MM and ALL groups was below 10-5 in 18% and 17%, below 10-4 in 17% and 4%, and under 10-3 in 17% and 9% of participants, respectively.

These real-world data demonstrate proof that MRD assessment as seen in the clinical trial setting is also adopted in the real-world setting and compliant with the NCCN guidelines for lymphoid cancers. Considering that MRD levels correlate with long-term outcomes in clinical trials and meta-analyses, highlighting this association in a large real-world patient population can provide further information needed to understand lymphoid malignancies better.

“The ability for NGS to assess response across a continuum of relevant MRD threshold levels is recommended in guidelines and is an important consideration for applying MRD testing in clinical practice,” wrote the study author led by Audrey Demaree, PharmD.

Reference:

Demaree A, Hewitt A, Eckert B, et al. Real-World Minimal Residual Disease (MRD) Assessment and Trends Using clonoSEQ in Acute Lymphoblastic Leukemia and Multiple Myeloma. Presented at: 2020 NCCN Virtual Annual Meeting; March 20–22, 2020: Orlando, FL, United States. Abstract 92.