The ANCHOR study is a phase 1/2 trial of melphalan flufenamide (melflufen) plus dexamethasone (DEX) and daratumumab (DARA) or bortezomib (BTZ) in patients with relapsed/refractory multiple myeloma (RRMM). The results of an analysis of the updated efficacy and safety data from the study are presented here.
Patients enrolled in this study had RRMM and were refractory to, or intolerant of, an immunomodulatory drug and/or a proteasome inhibitor. Patients had 1 to 4 prior lines of therapy. Patients in the DARA arm were excluded from the study if they had received prior anti-CD38 monoclonal antibody therapy. Patients in the BTZ arm were excluded if they were refractory to a proteasome inhibitor. Intravenous (IV) melflufen (30, 40, or 20 mg) was administered on day 1 of each 28-day cycle. In the DARA arm, IV DARA was administered 16 mg/kg once weekly (8 doses), every 2 weeks (8 doses), and then every 4 weeks + DEX 40 mg (20 mg if aged ≥75 years) weekly. In the BTZ arm, BTZ was administered 1.3 mg/m2 subcutaneously + DEX 20 mg (12 mg if aged ≥75 years) on days 1, 4, 8, and 11, + DEX 40 mg (20 mg if aged ≥75 years) on days 15 and 22. Patients were treated until they were determined to have progressive disease (PD) or exhibited unacceptable toxicity. The primary objective in phase 1 was to determine the optimal melflufen dose in any of the combinations and to assess overall response rate (ORR) in phase 2.
When the data was cut off in April of this year, a total of 33 patients had been treated with melflufen (30 mg, n = 6; 40 mg, n = 27) + DEX and DARA, and 10 patients had been treated with melflufen (30 mg, n = 3; 40 mg, n = 7) + DEX and BTZ. The median age of patients in the DARA arm was 63 years (range, 35-78 years), and the median number of previous lines of therapy was 2 (range, 1-4). High-risk cytogenetics was performed and was identified in 42% of patients. Among the study population, 79% of patients previously received frontline autologous stem-cell transplantation. Median treatment duration in this study was 8.4 months (range, 1.0-23.7 months). Thirty-six percent of patients discontinued treatment because of PD. The ORR was 70% (1 stringent complete response, 1 complete response, 10 very good partial responses [VGPRs], and 12 partial responses (PRs). Median progression-free survival was 12.9 months, and the median duration of response was 12.6 months. The most common grade 3/4 treatment-related adverse events (TRAEs) occurring in ≥5 patients were neutropenia (67%), thrombocytopenia (73%), and anemia (24%). A total of 12 (36%) patients experienced a serious TRAE. The most common serious TRAEs were influenza (9%), pneumonia (12%), parainfluenza virus infection (6%), and febrile neutropenia (6%). Four patients experienced fatal adverse events (myeloma progression and sepsis [2, 1 of which was considered possibly related to study treatment]. One patient experienced a general physical health deterioration, and 1 patient had chronic cardiac failure.
The median age of patients in the BTZ arm was 71 years (range, 61-82 years), and the median number of previous lines of therapy was 2.5 (range, 1-4). High-risk cytogenetics was performed and was identified in 40% of patients. Median treatment duration in this study was 5.6 months (range, 1.4-22.8 months). Two (67%) patients in the 30-mg cohort and 5 (71%) patients in the 40-mg cohort remained on treatment. A total of 3 patients were discontinued from the study: 2 resulting from PD and 1 because of lack of efficacy. The ORR was 60% (3 VGPRs and 3 PRs). The most common grade 3/4 TRAEs occurring in ≥2 patients were thrombocytopenia (80%), neutropenia (60%), and anemia (40%). A total of 6 (60%) patients experienced a serious TRAE. The most common serious TRAE was pneumonia (20%), and there were no deaths reported in this arm. The BTZ arm is still recruiting.
Among patients with RRMM, triple therapy with melflufen + DEX with BTZ or DEX with DARA demonstrated encouraging activity and was well-tolerated.
Abstract 417. ASH 2020. December 6, 2020. Melflufen plus dexamethasone (dex) and daratumumab (dara) or bortezomib (BTZ) in relapsed/refractory multiple myeloma (RRMM) refractory to an IMiD and/or a proteasome inhibitor (PI) - updated efficacy and safety.