Introduction

In April 2024, the journal Blood Science published an important study led by Dr. Gang An and colleagues from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, investigating the use of subcutaneous daratumumab in Chinese patients with relapsed/refractory multiple myeloma (R/R MM). Multiple myeloma is a challenging hematological malignancy characterized by the proliferation of abnormal plasma cells in the bone marrow. Despite significant advances in treatment, many patients experience relapse or develop resistance to existing therapies, necessitating new and more effective approaches.

Daratumumab, a monoclonal antibody that targets CD38, has become a cornerstone in the treatment of multiple myeloma. Traditionally administered intravenously, daratumumab has shown significant efficacy but is associated with long infusion times and a higher risk of infusion-related reactions (IRRs). To address these challenges, a subcutaneous (SC) formulation was developed, offering a more convenient and potentially safer alternative to the intravenous (IV) route.

The study conducted by Gang An and colleagues aimed to evaluate the safety, pharmacokinetics (PK), and efficacy of subcutaneous daratumumab in Chinese patients with RRMM. The phase 1, open-label, multicenter study enrolled 21 patients who had received at least two prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD). The primary goals were to assess the drug’s pharmacokinetics and safety, with secondary objectives focused on the overall response rate (ORR) and duration of response.

Study Design and Patient Population

The study included patients with a median age of 64 years, who were heavily pre-treated, with many being refractory to both PIs and IMiDs. The patients received a flat dose of 1800 mg subcutaneous daratumumab, administered weekly for the first two cycles, every two weeks for the next four cycles, and then every four weeks thereafter until disease progression or unacceptable toxicity. The reduced administration time of 3 to 5 minutes per injection provided a significant advantage over the traditional IV method, which could take several hours.

Key Findings

The study’s results were promising, demonstrating that subcutaneous daratumumab was well-tolerated with a safety profile consistent with previous studies. The most common treatment-emergent adverse events (TEAEs) were hematologic in nature, including anemia, leukopenia, and neutropenia, but these were manageable and aligned with expectations for this patient population. Importantly, the incidence of IRRs was low, with only one patient experiencing a mild IRR. Injection-site reactions were also minimal, further supporting the safety of the SC formulation.

（Blood Science 6(3):p e00193, July 2024. | DOI: 10.1097/BS9.0000000000000193）

Pharmacokinetic analysis revealed that subcutaneous daratumumab achieved adequate serum concentrations, comparable to those observed in global studies of the IV formulation. This finding supports the use of the SC route as a viable alternative, providing similar therapeutic effects with the added benefit of convenience.

Efficacy Outcomes

The overall response rate (ORR) in the study was 57.1%, with 38.1% of patients achieving a very good partial response (VGPR) or better, and 19.0% achieving a complete response (CR) or better. These results are in line with those observed in other studies of daratumumab, indicating that the subcutaneous formulation does not compromise efficacy.

Safety and Tolerability

The safety profile of subcutaneous daratumumab was consistent with the intravenous formulation, with no new safety concerns identified. The reduced risk of IRRs and shorter administration time make the SC formulation an attractive option for both patients and healthcare providers, potentially reducing the burden on healthcare systems and improving patient quality of life.

Significance and Future Directions

This study represents a significant advancement in the treatment of relapsed/refractory multiple myeloma, particularly for Chinese patients. The subcutaneous formulation of daratumumab offers a safer, more convenient alternative to the intravenous route, with similar efficacy and a reduced risk of adverse reactions. As the healthcare landscape continues to evolve, the adoption of subcutaneous daratumumab could become a standard practice, improving the treatment experience for patients with multiple myeloma.

Conclusion

The phase 1 study led by Dr. Gang An and colleagues demonstrates that subcutaneous daratumumab is a safe and effective treatment option for Chinese patients with relapsed/refractory multiple myeloma. With its favorable pharmacokinetic profile, reduced administration time, and low incidence of adverse reactions, subcutaneous daratumumab offers a promising alternative to the traditional intravenous formulation. These findings could lead to broader adoption of the SC formulation in clinical practice, ultimately enhancing patient care and outcomes in multiple myeloma.