65th ASH Annual Meeting
Theme 1: Practice-changing clinical trials
At this year’s ASH meeting, several potentially practice-changing study results were reported for newly diagnosed MM, R/R MCL, and R/R KMT2Ar acute leukemias in the late-breaking abstract session. Notably, ASH only accepts six late-breaking abstracts per year, which speaks to the quality of these data. The late-breaking abstracts in hematologic malignancies are highlighted below.
Newly Diagnosed MM
In the primary analysis of the Phase 3 PERSEUS trial, PFS, CR rates, and MRD negativity rates were significantly improved (P<0.0001) in patients with NDMM who received the anti-CD38 mAb daratumumab combined with VRd vs VRd alone, including in advanced‑stage and high-risk patient subgroups. The 58% improvement in PFS with the addition of daratumumab was described as “unprecedented” and the findings “practice‑changing,” supporting daratumumab + VRd followed by maintenance daratumumab + lenalidomide as a potential new SOC for transplant-eligible patients with NDMM.1 These findings were simultaneously published in NEJM.2
R/R MCL
In an interim analysis of the Phase 3 SYMPATICO trial, the addition of venetoclax to ibrutinib resulted in significant improvement (P≤0.01) in PFS (primary endpoint), CR rates, and TTNT in patients with R/R MCL.3 PFS was also generally consistent across patient subgroups. After AbbVie’s voluntary withdrawal of the accelerated FDA approval of ibrutinib monotherapy in R/R MCL earlier this year, the SYMPATICO data may pave a path to a new SOC treatment in R/R MCL.
R/R KMT2Ar Acute Leukemias
Patients with KMT2Ar acute leukemia have a particularly poor prognosis while receiving SOC therapy. A key driver of leukemogenesis in KMT2Ar acute leukemia is the interaction between menin and KMT2A fusion proteins; however, no approved therapies target this interaction. Interim results from the pivotal Phase 2 AUGMENT-101 study of revumenib, a novel small-molecule inhibitor of menin–KMT2A interactions, demonstrated high rates of ORR, MRD negativity, and subsequent HSCT in patients with R/R KMT2Ar acute leukemia.4 The study met its primary endpoint (CR + CRh rate); therefore, the study was stopped early in the KMT2Ar cohorts. Though revumenib is not yet FDA-approved, it is a likely treatment option for this patient population in the future.
ASH, American Society of Hematology; CR, complete response; CRh, complete response with partial hematologic recovery; FDA, US Food and Drug Administration; HSCT, hematopoietic stem cell transplantation; mAb, monoclonal antibody; MCL, mantle cell lymphoma; MM, multiple myeloma; MRD, measurable residual disease; NDMM, newly diagnosed multiple myeloma; NEJM, The New England Journal of Medicine; ORR, overall response rate; PFS, progression-free survival; R/R, relapsed/refractory; SOC, standard of care; TTNT, time to next treatment; VRd, bortezomib, lenalidomide, and dexamethasone.
1. Sonneveld P et al. ASH Annual Meeting 2023. Abstract LBA-1; 2. Sonneveld et al. N Engl J Med 2023; doi: 10.1056/NEJMoa2312054 [Epub ahead of print]; 3. Wang M et al. ASH Annual Meeting 2023. Abstract LBA-2; 4. Aldoss I et al. ASH Annual Meeting 2023. Abstract LBA-5.
