Encouraging and well-tolerated treatment efficacy was shown in patients with relapsed/refractory multiple myeloma (RRMM) in this analysis of updated efficacy and safety data from the ANCHOR study of melphalan flufenamide (melflufen) plus dexamethasone and daratumumab or bortezomib.
Provided in this article is an update of efficacy and safety from the phase 1/2 ANCHOR study of melflufen plus dexamethasone and daratumumab or bortezomib in patients with RRMM.
Included in this study were patients who had RRMM and were refractory to, or intolerant of, an immunomodulatory drug (IMiD) and/or a proteasome inhibitor (PI), with 1 to 4 prior lines of therapy. If patients in the daratumumab arm had received prior anti-CD38 monoclonal antibody therapy, they were excluded from the study. If patients in the bortezomib arm were PI refractory, they were excluded from the study. On day 1 of each 28-day cycle, melflufen (30, 40, or 20 mg intravenously [IV]) was administered. For patients in the daratumumab arm, daratumumab was administered 16 mg/kg IV once weekly (8 doses), every 2 weeks (8 doses), then every 4 weeks plus dexamethasone 40 mg (20 mg if aged ≥75 years) weekly. For patients in the bortezomib arm, bortezomib was administered 1.3 mg/m2 subcutaneously plus dexamethasone 20 mg (12 mg if aged ≥75 years) on days 1, 4, 8, and 11 plus dexamethasone 40 mg (20 mg if aged ≥75 years) on days 15 and 22. Patients were treated until progressive disease (PD) or unacceptable toxicity. In phase 1, the primary objective was to determine the optimal melflufen dose in combination and to assess overall response rate (ORR) in phase 2.
On April 6, 2020, at data cutoff, a total of 33 patients were treated with melflufen (30 mg, N = 6; 40 mg, N = 27) plus dexamethasone and daratumumab and 10 patients were treated with melflufen (30 mg, N = 3; 40 mg, N = 7) plus dexamethasone and bortezomib. In the daratumumab arm, median patient age was 64 years (range, 35-78 years), and median number of previous lines was 2 (range, 1-4). In 42% of patients, high-risk cytogenetics were identified. A total of 61% of patients were refractory to their last treatment, and 79% previously received frontline autologous stem-cell transplantation (ASCT). Median treatment duration was 8.4 months (range, 1.0-23.7 months), and 45% of the patients received ≥8 cycles. A total of 9 patients remained on treatment: 4 (67%) in the 30-mg cohort and 5 (19%) in the 40-mg cohort. Treatment discontinuation was primarily caused by PD (36%). The ORR was 70% (1 stringent complete response, 1 complete response, 10 very good partial responses [VGPRs], and 11 partial responses [PRs]). Median progression-free survival (PFS) was 11.5 months (95% confidence interval [CI], 6.7-not reached [NR]); median follow-up was 11.9 months. Median duration of response was 12.5 months (95% CI, 8.3-NR). Neutropenia (58%), thrombocytopenia (55%), and anemia (24%) were the most common grade 3/4 treatment-related adverse events (TRAEs), occurring in ≥5 patients. Grade 3/4 nonhematologic TRAEs were uncommon. A total of 12 (36%) patients experienced a serious treatment-emergent adverse event (TEAE). Influenza (9%), pneumonia (6%), parainfluenza virus infection (6%), and febrile neutropenia (6%) were the most common TEAEs. Fatal adverse events (myeloma progression and sepsis [1 patient; considered related to study treatment] and general physical health deterioration) were experienced by 2 patients.
The median age of patients in the bortezomib arm was 71 years (61-82 years); the median number of previous lines of therapy was 2.5 (1-4). In 40% of patients, high-risk cytogenetics were identified. Seventy percent of patients were refractory to their last treatment, 30% received prior frontline ASCT, and 90% received a prior PI. Median treatment duration was 5.6 months (1.4-22.8 months). A total of 7 patients remained on treatment: 2 (67%) patients in the 30-mg cohort and 5 (71%) patients in the 40-mg cohort. A total of 3 patients were discontinued from the study: 2 because of PD and 1 because of lack of efficacy. The ORR was 60% (3 VGPRs and 3 PRs). Data on PFS are premature. In this arm, no dose-limiting toxicities were observed. The most common grade 3/4 TRAEs occurring in ≥2 patients were thrombocytopenia (80%), neutropenia (60%), and anemia (40%); grade 3/4 nonhematologic TRAEs were uncommon. Serious TEAEs were experienced in 6 (60%) patients. Pneumonia (20%) was the most common TEAE, and no deaths were reported in this arm.
Triple therapy with melflufen plus dexamethasone with bortezomib or dexamethasone with daratumumab showed encouraging activity and was well-tolerated among patients with RRMM and poor prognostic factors.
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.