65th ASH Annual Meeting
Theme 4: Measurable residual disease assessment as a tool
Assessment of measurable residual disease, or MRD, has many applications in hematologic malignancies. This is evidenced by the numerous presentations at ASH 2023 on the use of MRD as a management tool across multiple histologies. These MRD tools have the potential to facilitate identification of high-risk patient subgroups, predict disease progression and survival outcomes, identify patients who may have equally successful outcomes with shorter treatment periods, and serve as surrogate endpoints. A sampling of this research is highlighted below.
Lymphoma
In the Phase 2 ELM-2 study, early MRD negativity based on ctDNA was highly associated with PFS in patients with FL and DLBCL receiving the CD20 × CD3 bispecific antibody odronextamab.1 ctDNA was also used to identify high-risk subgroups and enabled early prediction of progression in these patients. These findings suggest that early MRD status based on noninvasive ctDNA assessment could be used for response-directed treatment paradigms in the future.
CLL
The results of the Phase 3 FLAIR trial were shared in a highly anticipated oral presentation. In patients with untreated CLL, the combination of time-limited MRD-guided ibrutinib plus venetoclax significantly improved PFS and OS compared with FCR (P<0.005).2 MRD-guided treatment is expected to allow patients to enjoy treatment-free remission periods that limit toxicities while also reducing the likelihood of developing resistance to treatment.
FL3-ITD+ AML
In the Phase 3 QuANTUM-First study of the highly selective type II FLT3 inhibitor, quizartinib, FLT3‑ITD‑specific MRD measurements demonstrated potential prognostic utility in patients with FLT3‑ITD‑mutated AML.3 FLT3-ITD MRD negativity was associated with longer OS; quizartinib resulted in deeper responses and higher MRD negativity rates vs placebo. Thus, a deep and sustained reduction of FLT3-ITD+ leukemia burden may be responsible for some of the long‑term OS benefits seen with quizartinib in FLT3-ITD+ AML.
MM
In a plenary scientific session, the primary results of the Phase 3 randomized IsKia EMN24 trial were shared.4 Patients with transplant-eligible NDMM received either the anti‑CD38 mAb, isatuximab, combined with KRd (Isa-KRd) or KRd as pre-ASCT induction and post‑ASCT consolidation. Isa-KRd significantly increased MRD negativity rates vs KRd (P<0.05) (despite similar response rates), even in patients with high-risk cytogenetic abnormalities.4 Thus, MRD negativity may be a good surrogate endpoint in MM pending assessment of the correlation between depth of MRD negativity and PFS/OS outcomes.
AML, acute myeloid leukemia; ASCT, autologous stem cell transplantation; ASH, American Society of Hematology; CLL, chronic lymphocytic leukemia; ctDNA, circulating tumor DNA; DLBCL, diffuse large B-cell lymphoma; FCR, fludarabine-cyclophosphamide-rituximab; FL, follicular lymphoma; KrD, carfilzomib-lenalidomide-dexamethasone; MM, multiple myeloma; MRD, measurable residual disease; OS, overall survival; PFS, progression-free survival.
1. Arnason JE et al. ASH Annual Meeting 2023. Abstract 427. 2. Hillmen P et al. ASH Annual Meeting 2023. Abstract 631. 3. Perl A et al. ASH Annual Meeting 2023. Abstract 832. 4. Gay F et al. ASH Annual Meeting 2023. Abstract 4.