Adaptive Biotechnologies presented new data at the 66th ASH Annual Meeting demonstrating the impact of measurable residual disease (MRD) assessment using its next-generation sequencing-based clonoSEQ test in blood cancer clinical care and drug development. The data, featured in over 65 abstracts, highlight clonoSEQ's role in optimizing clinical care and improving outcomes for patients with various blood cancers.
MRD Testing in Mantle Cell Lymphoma
Phase 3 data from the ECOG-ACRIN EA4151 trial suggests that autologous hematopoietic cell transplantation (auto-HCT) may not provide additional benefit for mantle cell lymphoma (MCL) patients in first complete remission (CR) who have undetectable minimal residual disease (uMRD) at a sensitivity of 10^-6. Patients in CR with uMRD were randomized to receive either auto-HCT plus three years of maintenance rituximab or rituximab alone. Interim analysis, with a median follow-up of 2.7 years, showed no significant difference in overall survival (OS) between the two groups.
"Our study indicates that highly sensitive MRD testing, such as the clonoSEQ assay that we used, can potentially be used to tailor treatment decisions for patients with MCL," said Timothy Fenske, M.D., professor at the Medical College of Wisconsin. "By identifying patients in first complete remission who also have undetectable MRD status at 10^-6, we can potentially avoid the need for autologous hematopoietic cell transplantation, sparing them the associated risks and burdens."
Deep Molecular Remission in B-ALL
Data from the FELIX study indicates that achieving deep molecular remission, defined as MRD levels below 10^-6, correlates with improved outcomes in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) treated with obecabtagene autoleucel. The study found that 84% of treatment responders who had a clonoSEQ MRD test achieved MRD <10^-6. This result was associated with more durable responses, and higher event-free survival and OS rates than those observed in patients with MRD ≥10^-4 and between 10^-4 and 10^-6.
"Highly sensitive MRD testing provides a more accurate assessment of treatment response, allowing clinicians to make more informed decisions that can lead to improved long-term outcomes," said Elias Jabbour, M.D., professor of medicine at The University of Texas MD Anderson Cancer Center. "The findings from the FELIX study underscore the importance of incorporating highly sensitive MRD testing into routine clinical practice to optimize care for patients."
Blinatumomab in Pediatric B-ALL
A Phase 3 randomized trial evaluated the addition of blinatumomab to standard chemotherapy in pediatric patients with newly diagnosed standard-risk (SR) B-ALL. The study found that incorporating blinatumomab significantly improved disease-free survival compared to chemotherapy alone, establishing a new treatment standard for this patient population.
MRD Progression in Multiple Myeloma
A study identified 49 newly diagnosed multiple myeloma (MM) patients treated with a quadruplet regimen followed by autologous stem cell transplantation who experienced MRD progression as assessed by clonoSEQ. The median time from MRD progression to IMWG-defined disease progression was 10.1 months, supporting that rising MRD levels are an early indicator of impending clinical relapse in MM patients.
MRD-Adapted Therapy in CLL
A Phase 2 study evaluating the use of venetoclax and obinutuzumab in treatment-naïve CLL patients found that those achieving undetectable MRD (<10^-6) after nine cycles could discontinue therapy early. These patients had progression-free survival comparable to those who completed the standard 12 cycles, demonstrating the feasibility of MRD-guided treatment duration to minimize therapy exposure without compromising efficacy.
