In APOLLO, Subcutaneous Daratumumab With Pomalidomide Cuts Progression, Death Risk 37% in Relapsed MM

A version of daratumumab injected under the skin, when added to the oral medications pomalidomide and dexamethasone (D-Pd), cut the risk of disease progression or death by 37% compared with Pd alone in patients who have had at least 1 relapse with multiple myeloma, according to new study results.

Findings from the phase 3 APOLLO trial, which studied daratumumab and hyaluronidase-fihj, are being presented this weekend during the 62nd annual meeting of the American Society of Hematology and were featured in a press briefing on practice-changing results. The virtual meeting starts today and runs through Tuesday.

Daratumumab is an immunotherapy that targets the CD38 protein, which is heavily expressed in multiple myeloma cells. The therapy binds to the protein and blocks tumor cell growth, causing the cancerous cells to die. The subcutaneous formulation of daratumumab is approved in various combinations to treat transplant-eligible and refractory multiple myeloma, but not with pomalidomide (Pomalyst, Celgene), which is an anti-angiogenic and acts as an immunomodulator.

Janssen, which sells daratumumab as Darzalex, filed applications for with FDA and European regulators on November 12 based on the new results.

The study’s lead investigator, Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine in Greece, touted the subcutaneous formulation of daratumumab during a press briefing on APOLLO. The average time to inject the drug in APOLLO was 5 minutes, and Janssen reports that administration can take between 3 and 5 minutes.

Using the subcutaneous version can spare a patient 2 hours or more at a hospital or infusion center, Dimopoulos said. “This is an improvement in the quality of life of the patient,” he said, especially during the early stretch of the regimen when daratumumab is given weekly.

“Also, it saves valuable time in the chemotherapy or the outpatient treatment unit,” Dimopoulos said.

APOLLO randomized 304 patients; the average age of the study arm was 67 years and the average age of the Pd arm was 68 years. Patients had multiple myeloma and just over 4 years, and a slightly higher share of the Pd arm was considered high risk. Trial participants had received at least 1 prior line of therapy, including lenalidomide and a protease inhibitor, and had responded to the treatment but then progressed. Those with just 1 prior line of therapy were refractory to lenalidomide.

Among key findings from APOLLO:

• The study achieved its primary end point, significantly improving progression-free survival (PFS), with a hazard ratio (HR) of 0.63 (95% CI, 0.47-0.85; P = .0018).
• Patients in the D-Pd arm had a median PFS of 12.4 months, compared with 6.9 months for those in the Pd arm.
• Other results showed that patients taking D-Pd had a better rate of overall response (69% vs 46%), very good partial response or better (51% vs 20%), and compete response (25% vs 4%).
• A higher share of patients in the D-Pd arm achieved minimal residual disease negativity (9% vs 2%).

Among patients taking the subcutaneous version of daratumumab, 6% had infusion-related reactions, which were all grade 1 or 2, and 2% had local injection site reactions, all grade 1. Rates of patients who stopped treatment due to treatment-related adverse events were similar: 2% for D-Pd vs 3% for Pd.

Dimopoulos said these rates are far less than would be seen with infusion-related reactions, which can include upper respiratory tract reactions, including bronchospasm. An occasional patient develops hypotension; to avoid this, patients are typically premedicated during the first infusion, causing the session to last up to 8 hours. This creates a significant burden for patients and caregivers, he said.

In fact, he said, there are very few circumstances when intravenous administration of daratumumab would still be preferred.

Dimopoulous noted that these phase 3 results build on what was already known about daratumumab and pomalidomide as single agents in separate trials. The combination with both therapies has now been shown to be even more effective within the context of a randomized trial, he said. “This is a particularly useful regimen for an increasing number of patients with myeloma who progress on lenalidomide maintenance or continuous [therapy].”

APOLLO is one of several trials being presented at ASH that feature innovative treatments for multiple myeloma, an incurable blood cancer that affects plasma cells, causing tumors to grow in the bone marrow. Approximately 32,000 will be diagnosed with the disease in the United States this year, and 13,000 people will die from the disease. Multiple myeloma patients sometimes have no symptoms and the first sign of disease is a bone fracture; symptoms can include fatigue, pain, low red blood cell counts, or renal decline.

Reference

Dimopoulos MA, Terpos E, Boccadoro M, et al. Apollo: Phase 3 randomized study of subcutaneous daratumumab plus pomalidomide and dexamethasone (D-Pd) versus pomalidomide and dexamethasone (Pd) alone in patients with relapsed/refractory multiple myeloma (RRMM). Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020. Abstract 412. https://ash.confex.com/ash/2020/webprogram/Paper135874.html