Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma

Abstract

The efficacy and favorable safety profile of daratumumab monotherapy in multiple myeloma (MM) was previously reported. Here, we present an updated pooled analysis of 148 patients treated with daratumumab 16 mg/kg. Data were combined from part 2 of a first-in-human phase 1/2 study of patients who relapsed after or were refractory to ≥2 prior therapies and a phase 2 study of patients previously treated with ≥3 prior lines of therapy (including a proteasome inhibitor [PI] and an immunomodulatory drug [IMiD]) or were double refractory. Among the pooled population, patients received a median of 5 prior lines of therapy (range, 2 to 14 prior lines of therapy), and 86.5% were double refractory to a PI and an IMiD. Overall response rate was 31.1%, including 13 very good partial responses, 4 complete responses, and 3 stringent complete responses. The median duration of response was 7.6 months (95% confidence interval [CI], 5.6 to not evaluable [NE]). The median progression-free survival (PFS) and overall survival (OS) were 4.0 months (95% CI, 2.8-5.6 months) and 20.1 months (95% CI, 16.6 months to NE), respectively. When stratified by responders vs stable disease/minimal response vs progressive disease/NE, median PFS was 15.0 months (95% CI, 7.4 months to NE) vs 3.0 months (95% CI, 2.8-3.7 months) vs 0.9 months (95% CI, 0.9-1.0 months), respectively, and median OS was NE (95% CI, NE to NE) vs 18.5 months (95% CI, 15.1-22.4 months) vs 3.7 months (95% CI, 1.7-7.6 months), respectively. No new safety signals were identified. In this pooled data set, daratumumab 16 mg/kg monotherapy demonstrated rapid, deep, and durable responses, with a clinical benefit that extended to patients with stable disease or better.

Figure 1

Maximum change in paraprotein from baseline. In addition to reduction in paraprotein, International Myeloma Working Group criteria require (1) results from 2 consecutive tests demonstrating the necessary percent reduction in paraprotein, (2) reduction in paraprotein in both serum and urine, if measurable disease was determined by both serum and urine paraprotein, and (3) a ≥50% reduction in the size of soft tissue plasmacytomas, if these were present at baseline. Thus, ≥50% and ≥90% reduction in paraprotein do not correlate directly with PR and VGPR, respectively.

Figure 2

ORR in patient subgroups in the combined daratumumab 16 mg/kg group. Subgroup analysis of the overall best response in the 148 patients treated with daratumumab at a dose of 16 mg /kg. The dashed vertical line indicates 31.1%, which was the ORR in the total patient cohort. Exact 95% CIs are provided. International Staging System data are not available in GEN501 part 2. ALKY, alkylating agents, including autologous stem cell transplant; BORT, bortezomib; CARF, carfilzomib; CrCl, creatinine clearance; LEN, lenalidomide; POM, pomalidomide; THAL, thalidomide.

Figure 3

PFS in the combined daratumumab 16 mg/kg group. At a median follow-up of 20.7 months, the median PFS of patients in (A) the combined data set and (B) stratified by response category are shown.

Figure 4

OS in the combined daratumumab 16 mg/kg group. The median OS of patients in (A) the combined data set and (B) stratified by response category are shown.