From the Guidelines
Daratumumab refractory disease is defined as multiple myeloma that has progressed during or within 60 days after completing daratumumab-containing therapy, as identified in the NCCN clinical practice guidelines in oncology, version 2.2024 1. This definition is crucial in clinical practice as it determines the next line of treatment for patients who no longer respond to daratumumab.
- The NCCN guidelines provide evidence-based recommendations for the treatment of multiple myeloma, including the use of daratumumab in combination with other agents such as pomalidomide and dexamethasone 1.
- Studies have shown that the combination of daratumumab/pomalidomide/dexamethasone is effective in patients with relapsed/refractory multiple myeloma, with an overall response rate (ORR) of 60% and a median progression-free survival (PFS) of 8.8 months 1.
- However, patients who progress during or after daratumumab treatment are considered refractory and require alternative treatment options, such as immunomodulatory drugs, proteasome inhibitors, or newer therapies like BCMA-targeted treatments 1.
- The emergence of daratumumab resistance represents a challenging clinical scenario, and treatment options should be guided by the most recent and highest-quality evidence, prioritizing morbidity, mortality, and quality of life as outcomes.
- In clinical practice, the definition of daratumumab refractory disease is essential to determine the best course of treatment and to improve patient outcomes, as highlighted in the NCCN guidelines 1.
From the Research
Daratumumab Refractory Definition
- Daratumumab refractory multiple myeloma refers to a condition where patients with multiple myeloma develop resistance to daratumumab, a monoclonal antibody targeting CD38 2.
- The definition of daratumumab refractoriness is not explicitly stated in the provided studies, but it can be inferred as a condition where patients no longer respond to daratumumab treatment, either due to primary or secondary resistance 3.
- Studies have shown that patients who are refractory to daratumumab can still achieve responses with retreatment, especially when combined with other anti-myeloma drugs 3, 4.
Clinical Efficacy of Daratumumab Retreatment
- A study published in the European Journal of Haematology found that daratumumab-based retreatment (D2) in patients with daratumumab-refractory multiple myeloma resulted in a response rate of 49% and a median progression-free survival of 7.97 months 3.
- Another study published in Leukemia & Lymphoma found that pomalidomide, dexamethasone, and daratumumab given immediately after early-line lenalidomide-based treatment demonstrated safety and efficacy, with an overall response rate of 77.7% and a median progression-free survival of 30.8 months 4.
Daratumumab Plus Pomalidomide and Dexamethasone
- The APOLLO trial, published in The Lancet Oncology, found that daratumumab plus pomalidomide and dexamethasone significantly improved progression-free survival compared to pomalidomide and dexamethasone alone in patients with previously treated multiple myeloma 5.
- An updated analysis of the APOLLO trial, published in The Lancet Haematology, found that the median overall survival was 34.4 months in the daratumumab plus pomalidomide and dexamethasone group versus 23.7 months in the pomalidomide and dexamethasone group, although the difference was not significant 6.