Abstract 4529: Antibody-drug conjugates for the treatment of hematologic malignancies

Abstract Belantamab mafodotin is composed of a monoclonal antibody targeting BCMA and is conjugated to the cytotoxic payload monomethyl auristatin F (MMAF), a microtubule disrupting agent, and is approved for multiple myeloma. Its efficacy was evaluated in DREAMM-7, an open-label, randomized trial in adults with R/R multiple myeloma with at least one prior therapy. The mPFS was 31.3 months (95% CI: 23.5, NR) in the BVd arm and 10.4 months (95% CI: 7, 13.4) in the DVd arm (HR 0.31, 95% CI: 0.21, 0.47). The mOS was NR and 35.7 months (95% CI: 21.1, NR) in respective arms (HR 0.49, 95% CI: 0.32, 0.76). Gemtuzumab oxogamicin targets the CD33 receptor on myeloid cells and is approved for AML. Its approval in combination with CT for adults was based on ALFA-0701, a multicenter, randomized, open-label phase 3 study of 271 patients with newly-diagnosed, de novo AML. The second trial, MyloFrance-1, a phase 2, single-arm, open-label study, included 57 patients with CD33-positive AML in first relapse. Fifteen (26%; 95% CI: 16% - 40%) patients achieved CR following a single course of gemtuzumab ozogamicin. Inotuzumab ozogamicin targets the CD22 receptor on B-cell precursor leukemic cells and is approved for ALL in pediatric patients with R/R CD22-positive B-cell precursor ALL. Efficacy was evaluated in a multicenter, single-arm, open-label study and the main efficacy outcome measures were complete remission (CR), duration of CR, and the proportion of patients with MRD negative CR. CR was defined as 5% blasts in the bone marrow and the absence of peripheral blood leukemia blasts, full recovery of peripheral blood counts and resolution of any extramedullary disease. MRD was defined by leukemic cells comprising 1 × 10-4 (0.01%) of bone marrow nucleated cells. 22/53 (42%, 95% CI: 28.1, 55.9%) achieved CR and the median duration of CR was 8.2 months (95% CI: 2.6, NE). The MRD negativity rate in patients with CR was 21/22 95.5% (95% CI: 77.2, 99.9) based on flow cytometry, and 19/22 86.4% (95% CI: 65.1, 97.1 based on RQ-PCR. Brentuximab vedotin is composed of a monoclonal antibody targeting the CD20 antigen and conjugated to microtubule disrupting agent monomethyl auristatin, which serves as the payload, for chronic Hodgkin’s lymphoma. Approval was based on ECHELON-3, a randomized, double-blind, placebo-controlled trial enrolling 230 adult patients with R/R LBCL who were ineligible to receive an auto-HSCT or CAR T-cell therapy. The major efficacy outcome measure was OS. Additional efficacy outcome measures included PFS and ORR. The trial demonstrated a statistically significant improvement in OS, PFS and ORR. mOS of 13.8 months (95% CI: 10.3, 18.8) in the BV+R2 arm and 8.5 months (95% CI: 5.4, 11.7) in the Pbo+R2 arm (HR 0.63, 95% CI: 0.45, 0.89) were shown. mPFS was 4.2 months (95% CI: 2.9, 7.1) with BV+R2 and 2.6 months (95% CI: 1.4, 3.1) with Pbo+R2 (HR 0.53, 95% CI: 0.38, 0.73). The ORR was 64.3% (95% CI: 54.7, 73.1) and 41.5% (95% CI: 32.5, 51.0), respectively. Citation Format: Priya Hays. Antibody-drug conjugates for the treatment of hematologic malignancies abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4529.