Subcutaneous daratumumab plus pomalidomide and dexamethasone in R/R MM

In the first phase 3 study evaluating subcutaneous (SC) daratumumab combination therapy in multiple myeloma (MM), the combination of daratumumab and pomalidomide plus low-dose dexamethasone (Pd) significantly reduced the risk of progression or death versus Pd alone in patients with relapsed/refractory (R/R) MM who had received ≥1 prior line of therapy [1].

Daratumumab is a CD38-targeted monoclonal antibody (mAb) approved as monotherapy and in combination with standard-of-care regimens for patients with newly diagnosed or R/R MM.

In a phase 1b study, intravenous (IV) daratumumab plus Pd induced durable responses and was well tolerated in patients with heavily pretreated R/R MM, including those with prior lenalidomide treatment [2]. Based on these results, daratumumab-Pd is approved in the United States for the treatment of R/R MM patients with ≥2 prior lines of therapy, including lenalidomide and a proteasome inhibitor.

The SC formulation of daratumumab has demonstrated similar efficacy and safety profiles as IV daratumumab. The efficacy and pharmacokinetics of SC daratumumab are non-inferior to IV daratumumab. In addition, SC daratumumab has lower rates of infusion-related reactions and a considerably shorter administration duration of 5 minutes [3]. The phase 3 APOLLO study (NCT03180736) evaluated daratumumab SC plus Pd versus Pd alone in 304 R/R MM patients who had received ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor. Prof. Meletios Dimopoulos (University of Athens, Greece) presented results of the primary analysis of APOLLO.

The primary endpoint of median progression-free survival (PFS) for the daratumumab-Pd versus Pd arm was 12.4 versus 6.9 months, respectively (HR 0.63; 95% CI 0.47-0.85; P=0.0018; see Figure) [1]. Moreover, daratumumab-Pd achieved longer PFS among patients who were refractory to lenalidomide (9.9 vs 6.5 months). Daratumumab-Pd achieved significantly deeper responses versus Pd alone, including a >6 times higher complete response (CR) rate (25% vs 4%) and a >4 times higher minimal residual disease (MRD)-negativity rate (9% vs 2%). Daratumumab-Pd had a manageable safety profile, consistent with the known safety profile of SC daratumumab and Pd alone. No new safety concerns were observed.

Figure: PFS at a median follow-up of 16.9 months [1]



PFS, progression-free survival; D, daratumumab; Pd, dexamethasone

This data demonstrates that daratumumab-Pd is effective and convenient for patients with R/R MM who received ≥1 prior therapy, including lenalidomide and a proteasome inhibitor [1].

1. Dimopoulos MA, et al. Apollo: Phase 3 Randomized Study of Subcutaneous Daratumumab Plus Pomalidomide and Dexamethasone (D-Pd) Versus Pomalidomide and Dexamethasone (Pd) Alone in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM). 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 412.
2. Chari A, et al. Blood. 2017;130:974-81.
3. Mateos M-V, et al. Lancet Haematol. 2020;7:e370-e380.

Posted on 18 February 20214 September 2023