At the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California, Alexey Danilov, MD, City of Hope National Medical Center, La Canada Flintridge, California, analyzes the prognostic value of undetectable minimal residual disease (uMRD) for progression-free survival among patients with follicular lymphoma (FL) who had received initial chemotherapy treatment. Danilov and coauthors noted that this trial for the first time demonstrated that uMRD status, as evaluated by Clonoseq, “predicts improved 5- and 10-year [progression-free survival] in patients with FL initially treated with chemoimmunotherapy.”

Transcript:

My name is Alexey Danilov. I'm a professor in the Department of Hematology and the leader of the Lymphoma Center at City of Hope, National Medical Center in Los Angeles, California. I will talk to you today about the study results that we presented at ASH 2023 on minimal residual disease assessment and follicular lymphoma. 

Minimal residual disease assessment has made significant progress in the past few years in many lymphoma subtypes. For example, in chronic lymphocytic leukemia, we use both flow cytometry-based and molecular analysis-based assays. In mantle cell lymphoma, molecular [assays] have been introduced, which help us assess response. However, in follicular lymphoma, no assay so far has been established and reliably used in [the] assessment of molecular minimal residual disease, or MRD. MRD is important [in the] prognostication and the hope is that it'll be important in determining subsequent therapy or duration of therapy in these patients in the future. 

We analyzed MRD in patients treated in [the] Southwestern Oncology Group (SWOG) S0016 study where patients received the combination of chemotherapy [cyclophosphamide, doxorubicin, vincristine, and prednisone] (CHOP) with either rituximab or radioimmunotherapy. We analyzed minimal residual disease by clonoSEQ-based assay which essentially looks at the unique rearrangement of patients’ light and heavy chain B-cell receptor genes. We analyzed it at baseline on lymph node biopsy tissue in patients with newly diagnosed follicular lymphoma [who] were treated with these regimens. 

Then, 1 year later in the bone marrow biopsy, we analyzed it again, and that was essentially our assessment of minimal residual disease at that point to determine the depth of response, also prognosticate, further. The primary endpoint was progression-free survival at 5 years. We found a couple of things. 

The first important finding is that there was still a failure of the assay in about 29-30% of cases, and this is because [of] follicular lymphoma---due to it---but the genesis, significant somatic hypermutation. There is some instability in the genetic rearrangements that patient cells are experiencing over time. In about 30% of cases, we were not necessarily able to reliably determine the MRD status after a year of therapy. However, in the remaining 70% of patients, the majority of them were MRD-negative in the bone marrow. There was a fraction [that] could remain MRD-positive by the clonoSEQ assay, and what's important [is] that MRD status predicted progression-free survival at both a 5-year time point and [a] 10-year time point. 

Now, we have a really long follow-up on this study, which stretches out to 15 years, and MRD status predicts progression-free survival at both 5-year and 10-year time points. It did not predict overall survival likely due to the fact that it is an indolent lymphoma and patients now do have good options to treat this disease. But, this key finding indicates that MRD can be used in the future for prognostication and potentially determining the duration and direction of therapeutic approaches in follicular lymphoma.

Source: 

Danilov A, Li H, Shadman M, et al. Minimal residual disease (MRD) status predicts outcomes in patients with follicular lymphoma (FL) treated with chemo-immunotherapy on SWOG S0016. Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 4359