Update for the ‘Watch’ Registry, a Real-World Observational Study Using Clonoseq® to Monitor MRD in Lymphoid Malignancies
Authors: Cowan Andrew J. , Patel Krish , Svoboda Jakub , Shah Bijal D. , Cheson Bruce D. , Azzi Georges , Rabara Viral , Muffly Lori S. , Simmons Heidi , Thuillier Stephen , Leonard Jessica T. 
Published: December 2023

Background: For patients with the most common B-cell malignancies, assessment of minimal/measurable residual disease (MRD) is routinely incorporated into clinical trials to evaluate patient response and NCCN guidelines include recommendations for incorporation of MRD assessment into clinical practice for ALL, CLL, and MM. Despite that, there is a desire for additional data that reflect the impact of MRD assessment in patient management in the real-world setting. The Watch Registry (NCT04545333) is a prospective, multicenter observational study being conducted in the US to collect data from health care providers who use the clonoSEQ MRD assay as part of routine care for their lymphoid malignancy patients. Data collection is focused on understanding broad practice patterns for clonoSEQ® MRD assessment, including assay timing and subsequent treatment decisions. The ultimate goal of the study is to describe the implementation and impact of the assay in patient management. Here we describe the latest updates from this ongoing study.

Methods: Eligible patients are ≥ 18 years old, diagnosed with NHL, MM, ALL, or CLL, not enrolled in an interventional clinical study that dictates the frequency of their MRD testing, and whose treating physician is currently or planning to use clonoSEQ to monitor their MRD as part of their routine management. Patients may be in any phase of treatment at enrollment. Enrollment is now closed and follow-up will continue through December 31, 2024.

Results: From October 2020 through data cutoff of June 21, 2023, 465 patients were enrolled across 18 academic and community sites (463 patients with reportable data). Enrollment by disease is 70 ALL, 109 CLL, 140 MM, 34 DLBCL, 27 MCL, 54 FL and 29 other lymphoid malignancies. Of these patients, 91 (20%) have discontinued the study; the most common reasons are death (35; 8%) and failure to detect trackable sequences by clonoSEQ (23; 5%). Other reasons include site closure and patient/physician decision to withdraw. Patients range in age from 18 to 92, 57% are male, and the mean lines of therapy (LOT) prior to enrollment is ~2. The median follow up period is 14 months.

To date, 994 clonoSEQ MRD tests have been ordered and 74.5% of patients have received at least 1 MRD test (Table 1). The most frequent testing was reported for ALL patients (4.8 tests/pt) followed by CLL (2.9 tests/pt), MCL (3.3 tests/pt), other lymphoid malignancies (2.9tests/pt), DLBCL (2.6 tests/pt), FL (2.1 tests/pt) and MM (2.2 tests/pt). Across all disease cohorts, most MRD tests were ordered during remission (71.4%). In the ALL cohort, a larger proportion of tests were ordered at other treatment timepoints relative to other disease cohorts: end of induction (6%), pre-HSCT (6%), post-HSCT, including some post-HSCT monitoring (42%) and post-CAR-T (6%). Across all cohorts, 220 patients (48%) had multiple MRD tests ordered with the largest proportion observed in the ALL cohort (67%), followed by MCL (63%), DLBCL (50%), CLL (48%), other lymphoid malignancies (45%), MM (39%) and FL (35%). For patients tested during monitoring, the number of tests/pt was generally larger among patients with ≥1 prior LOT compared to patients with 0 prior LOT.

With 979 test results reported (Table 2), there were 583 tests with residual sequences detected (59.5%) and 396 with no residual sequences detected (39.5%). Based on the presence of residual sequences, a change to a patient's treatment plan was reported 66 times (11.3%) and there were 52 separate reports (11.1%) of a change to the frequency of future MRD monitoring. Specific treatment changes included 56 instances of therapy intensification (9.6%) and 10 instances of therapy de-intensification (1.7%). In the case where no change was made based on the presence of residual sequences, reported reasons for not making a change (if reported) included decreasing MRD (24%) and low/stable disease (10.9%).

Conclusions: Clinicians are using clonoSEQ to assess MRD across multiple lymphoid malignancies in routine care. In ALL, MRD testing was reported for multiple treatment timepoints whereas in other disease states (CLL, MM, NHL) reported use of the assay was predominantly for monitoring remission. The advent of therapeutic regimens for B-cell malignancies with higher relative response rates denotes the need for sensitive tools that can be used in clinical practice to better assess treatment response and monitor MRD to facilitate future treatment decisions.