For patients with relapsed or refractory multiple myeloma whose disease progressed after at least one prior regimen, the subcutaneous form of daratumumab, given with pomalidomide and dexamethasone, significantly improved progression-free survival vs pomalidomide and low-dose dexamethasone alone. Findings from the primary analysis of the phase III APOLLO study were presented by Meletios A. Dimopoulos, MD, and colleagues at the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 412).

Meletios A. Dimopoulos, MD

In a press briefing in advance of the meeting, Dr. Dimopoulos, of National and Kapodistrian University of Athens in Greece, reported that the triplet (D-Pd) significantly reduced disease progression by 37% (P = .0018) over pomalidomide/dexamethasone (Pd) alone.

Median progression-free survival was 12.4 months with D-Pd vs 6.9 months with Pd (hazard ratio [HR] = 0.63; P = .0018). Patients treated with D-Pd also achieved significantly deeper responses, including a six-times higher rate of complete response and a four-times higher rate of minimal residual disease (MRD) negativity vs patients treated with Pd alone, he said.

In addition, Dr. Dimopoulos pointed out, “The rate of infusion reactions was very low and the duration of administration short, thus increasing convenience for patients and decreasing treatment burden.”

The findings lend support for the use of subcutaneous daratumumab over the intravenous form.

Press briefing moderator Robert A. Brodsky, MD, Professor of Medicine and Oncology and Director of the Division of Hematology at Johns Hopkins School of Medicine, agreed, saying, “Subcutaneous daratumumab is a big advance and has a high likelihood of changing practice.”

Robert A. Brodsky, MD

Another Step Along the Daratumumab Path

Daratumumab is an anti-CD38 monoclonal antibody with multiple modes of action. It has activity as both a single agent and when combined with other standard regimens.

The subcutaneous formulation of daratumumab has a similar safety profile as intravenous daratumumab, though it is associated with significantly fewer infusion-related reactions and has a considerably shorter administration time of 5 minutes. Subcutaneous daratumumab is approved for use in the United States, the European Union, Canada, and Korea.

About APOLLO

The phase III open-label, multicenter APOLLO study, conducted by the European Myeloma Network, enrolled 304 patients with relapsed or refractory multiple myeloma who had received one or more prior lines of therapy including lenalidomide and a proteasome inhibitor.

Patients were typical of the relapsed/refractory myeloma population. Most were aged 65 or older; approximately one-third had high cytogenetic risk; and about half had stage II or III disease as classified by the International Staging System (ISS). The median number of prior lines of therapy was two. Nearly 80% of patients were refractory to lenalidomide, 48% were refractory to a proteasome inhibitor, and 42% were refractory to both.

All patients received 28-day treatment cycles that included pomalidomide at 4 mg daily plus dexamethasone at 40 mg on days 1, 8, 15, and 22 (20 mg for patients aged ≥ 75 years). For patients treated with the D-Pd regimen, 1,800 mg of daratumumab coformulated with recombinant human hyaluronidase PH20 (rHuPH20) was given weekly for cycles 1 to 2, every 2 weeks for cycles 3 to 6, and every 4 weeks thereafter.

The primary endpoint was progression-free survival. Median duration of treatment was 11.5 months with D-Pd vs 6.6 months with Pd.

Study Meets Primary Endpoint

Dr. Dimopoulos presented the primary analysis, which was performed after 190 progression-free survival events at a median follow-up of 16.9 months. At that time, median progression-free survival was 12.4 months with D-Pd vs 6.9 months with Pd (HR = 0.63; P = .0018), thus meeting the study’s primary endpoint.

In patients who were refractory to lenalidomide, median progression-free survival was 9.9 months vs 6.5 months. At 12 months, the progression-free survival rate was 52% in the daratumumab arm vs 35% in the control arm.

“This benefit was essentially seen across all subgroups of patients, including younger and older patients, patients with different ISS stages, regardless of prior line of therapy, regardless of lenalidomide refractoriness, and regardless of cytogenetic risk,” noted Dr. Dimopoulos.

The triplet was also superior to pomalidomide/dexamethasone in terms of other endpoints, including overall response (69% vs 46%), very good partial response or better (51% vs 20%), complete response (25% vs 4%), and minimal residual disease negativity (9% vs 2%).

Safety Profile

The most common grade 3 or 4 treatment-related adverse events for D-Pd and Pd were neutropenia (68% vs 51%), leukopenia (17% vs 5%), lymphopenia (12% vs 3%), febrile neutropenia (9% vs 3%), pneumonia (13% vs 7%), and lower respiratory tract infections (11% vs 9%). Infusion-related events were rare, seen in 6% of patients treated with D-Pd; local injection-site reactions (all grade 1) were seen in 2% of this arm.

Rates of study treatment discontinuation due to treatment-related adverse events were similar for the D-Pd vs Pd arms (2% vs 3%). Rates of treatment-related adverse events leading to death were similar (7%), as was the incidence of second primary malignancies (2%). 

D-Pd had a manageable toxicity profile consistent with the known safety profiles of daratumumab, pomalidomide, and dexamethasone.

“In this phase III study evaluating subcutaneous daratumumab plus Pd, D-Pd significantly reduced the risk of progression or death by 37% in patients with relapsed or refractory multiple myeloma who had received one or more prior line[s] of therapy vs Pd alone. No new safety concerns were observed. The infusion-related reaction rate was very low and administration duration short, thus increasing convenience for patients and decreasing treatment burden. Collectively, these data show that D-Pd is an effective and convenient treatment for patients with relapsed or refractory myeloma who received one or more prior therap[ies], including lenalidomide and a proteasome inhibitor.”

Disclosure: For full disclosures of the study authors, visit ash.confex.com.