Interim Update on the ‘Watch’ Registry, a Real-World Observational Study Using Clonoseq® to Monitor MRD in Lymphoid Malignancies

Background: Clinical trials of investigational agents in B-cell malignancies have demonstrated significant improvements in efficacy over the past several years. Despite often high complete response rates, many patients still relapse. All relapses are caused by residual tumor cells, whether detectable by standard clinical assessments or not. To detect low-level disease burdens, known as minimal/measurable residual disease (MRD), highly sensitive technologies are needed. The clonoSEQ® Assay has been cleared by the FDA to detect MRD in the bone marrow of patients with acute lymphoblastic leukemia (ALL) and multiple myeloma (MM) and in blood or bone marrow for patients with chronic lymphocytic leukemia (CLL). clonoSEQ is also available as a laboratory developed test (LDT) to detect MRD in other B-cell malignancies including non-Hodgkin lymphoma (NHL) and in additional sample types such as blood and plasma.

Methods: The Watch Registry (NCT04545333; recruiting) is a prospective, multicenter observational study being conducted in the US to collect data from health care providers who use clonoSEQ as part of routine care for their ALL, MM, CLL, and NHL patients. Data collection is focused on understanding the timing of clonoSEQ MRD assessment and subsequent treatment decisions made based upon those results. The ultimate goal of the study is to describe the implementation and impact of the assay in patient management.

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. Planned enrollment is 528 patients with a target of 476 who have ≥ 1 clonoSEQ MRD test during the course of the study.

Results: From October 2020 through data cutoff of June 22, 2022, 328 patients have been enrolled across 18 sites (both academic and community). Twenty-three patients have discontinued for reasons including death (9), early site closure (5), failure to detect trackable sequences by clonoSEQ (4), insufficient “ID” sample material (2), enrollment on interventional study (1), site decision (1), patient decision (1). Patients range in age from 18-92 yrs with 136 females and 192 males. Patients have had 0-12 prior lines of therapy. Enrollment by tumor type is 52 ALL, 82 CLL, 94 MM, 82 NHL (32 FL, 27 DLBCL, 23 MCL), and 18 with less common lymphoid malignancies. Time on study ranges from 0.3 to 20.5 months with a median follow up of 6.0 months.

To date, 295 clonoSEQ MRD tests have been ordered overall (Table 1) with 188 (63.7%) patients having had ≥ 1 MRD test on study and a range of 0-11 per patient. For those patients who have been tested to date, the most frequent use has been for patients with ALL (2.85 tests/pt) followed by NHL (1.30 test/pt), MM (1.11 tests/pt), and CLL (1.10 tests/pt). Most (74.9%) MRD tests have been ordered during remission (49.2%) or as the first MRD assessment post-hematopoietic cell transplant (HCT; 25.8%). Other timepoints include end of induction (2.7%), pre-HCT (2.7%), and other reasons (16.9%; includes post-chimeric antigen receptor T cell [CAR-T] monitoring).

With 272 clonoSEQ results reported as of data cutoff (Table 2), there were 23 (8.5%) positive, 120 (44.1%) positive below limit of detection (LOD), and 129 (47.4%) negative results. Changes to a patient’s treatment plan based upon MRD results have been made 31 (11.4%) times. Changes include initiating next line of therapy in 22 (8.1%) instances, intensifying ongoing treatment in 5 instances (1.8%), and reducing treatment intensity in 4 (1.5%) instances. The frequency of future MRD monitoring was changed based upon clonoSEQ results 29 (10.7%) times with 20 (7.4%) instances of an increase in monitoring frequency and 9 (3.3%) decreases.

Details of treatment regimens and changes are being collected and will be reported at a later date.

Conclusions: MRD is being measured by clonoSEQ across lymphoid malignancies in routine care, and reportedly, mostly for the purpose of monitoring MRD levels during remission (maintenance therapy or observation). With the readout of the many ongoing trials that are assessing the use of MRD to determine treatment regimen or discontinuation across these tumor types, using MRD to inform such decisions in real-world practice will become more common.