FDA clears first in vitro diagnostic MRD assay for CLL

The U.S. Food and Drug Administration (FDA) has approved the first and only assay – clonoSEQ®, to screen and assess minimal residual disease (MRD) in patients with chronic lymphocytic leukemia (CLL). This diagnostic test was approved following positive results from two important clinical trials, the Phase III CLL14 study (NCT02242942) and a Phase II trial (NCT00759798), based on its ability to “detect 1 single cancer cell among a million healthy cells.”1-3

CLL is a form of leukemia in which the bone marrow creates lymphocytes in excess. CLL is one of the most prevalent forms of leukemia in adults and is considered incurable, with patients often needing additional treatment due to relapse.

Cancerous cells may be present at such low levels that current methods are unable to identify them, calling for more refined and sensitive techniques. MRD evaluation is performed regularly throughout a patient’s cancer journey, to assess their prognosis, monitor response to treatment, observe disease during remission and predict potential relapse.4

This new FDA-cleared assay is an in vitro diagnostic tool for the detection and monitoring of MRD in CLL based on immunosequencing, a platform technology that allows the enumeration, specification and quantification of each and every B-and/or T-cell in any biologic sample of interest.4

Research from the CLL14 trial indicated that when using clonoSEQ®, those with undetectable MRD three months after treatment had almost a seven-fold reduced risk of disease progression, when compared with patients that were unable to reach undetectable MRD (n = 377).2  For the purpose of the study, undetectable MRD was defined as a level of 1 cancer cell among 100,000 healthy cells.1,5

Additionally, results from 30 months post-treatment showed that the probability of disease progression for evaluable patients with undetectable MRD was only 5%, as compared to 36% for patients with detectable disease.2

Furthermore, in the Phase II trial, patients exhibiting MRD negativity once treatment concluded had superior progression-free survival (PFS) compared with those who had detectable MRD, regardless of the kind of sample that was tested (bone marrow: median not reached [NR] vs 67 months, P = .02; peripheral blood: median NR vs 74 months, P = .02) and the threshold at which MRD was assessed.3

“I should say that the data with the use of that assay in CLL patients is still limited but certainly provides a flexibility in approach to measure very deep level of MRD. ”

Nitin Jain, MD of The University of Texas MD Anderson Cancer Center, Houston, TX.

The clonoSEQ® provides an accessible assay through the use of a blood sample to test for MRD in patients with CLL.5  However, the company is aware that the frequency of hospital visits has declined due to COVID-19, and as a solution has provided alternative options for blood sample collection, including home samples taken by qualified professionals and minimal-content blood collection at Patient Service Centers throughout the United States.1

“We believe the first-time clearance of clonoSEQ® in blood will be advantageous for both providers and patients. Given the risks that COVID-19 poses for [patients with] cancer, we are proud to be collaborating with 2 best-in-class service providers to offer patients flexible and safe options for blood sample collection outside of a hospital or clinic.”

Lance Baldo, chief medical officer of Adaptive Biotechnologies.5

The FDA clearance represents an important milestone for the CLL community, paving the way for improved diagnosis and reduced diagnostic error. ClonoSEQ® allows both clinicians and patients a more convenient and less intrusive way to pinpoint the current disease burden and help them plan for the future.

This novel tool makes deeper and more durable responses achievable for many patients with hematological malignancies, providing a very promising alternative to the traditional CLL diagnostic options.

Written by Frankie Lewns

Edited by Tom Southgate

  1. OncLive. FDA Clears First MRD Assay for Chronic Lymphocytic Leukemia. Available from: https://www.onclive.com/view/fda-clears-first-mrd-assay-for-chronic-lymphocytic-leukemia (Last accessed 24/08/20).
  2. Al-Sawaf O, Zhang C, Tandon M, et al. Fixed-duration venetoclax-obinutuzumab for previously untreated patients with chronic lymphocytic leukemia: follow-up of efficacy and safety results from the multicenter, open-label, randomized phase III CLL14 trial. J Clin Oncol. 2020;38(suppl 15):8027. 
  3. Thompson PA, Srivastava J, Peterson C, et al. Minimal residual disease undetectable by next-generation sequencing predicts improved outcome in CLL and chemoimmunotherapy. Blood. 2019;134(suppl 22):1951-1959. doi:10.1182/blood.2019001077.
  4. Ilan Kirsch. Immune monitoring technology primer: immunosequencing. J Immunother Cancer. 2015;3(suppl 29).
  5. Adaptive Biotechnologies Receives Expanded FDA Clearance for the clonoSEQ® Assay to Assess Minimal Residual Disease (MRD) in Patients with Chronic Lymphocytic Leukemia. News release. Adaptive Biotechnologies Corporation. August 6, 2020. Available from: https://investors.adaptivebiotech.com/node/7696/pdf (Last accessed 24/08/20).