Combination Treatment Maintains Quality of Life in Relapsed/Refractory MM

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Health-related quality of life was maintained when treating relapsed/refractory multiple myeloma (RRMM) with daratumumab in combination with bortezomib and dexamethasone.

Results from patient reports indicate that health-related quality of life was maintained when treating relapsed/refractory multiple myeloma (RRMM) with daratumumab (Darzalex) in combination with bortezomib (Velcade) and dexamethasone, according to a new study.

Previously reported results from the phase 3 CASTOR trial (NCT02136134) had demonstrated that adding daratumumab to the combination of bortezomib and dexamethasone extended progression-free survival when compared to solely using the chemotherapy and steroid. The additional information of patient-reported outcomes (PROs) from the CASTOR trial, published this month in the British Journal of Haematology, amplifies the clinical findings on the 3-drug combination’s benefits.

Daratumumab is an anti-CD38 monoclonal antibody with a direct on-tumor and immunomodulatory mechanism of action.

Patients in the group taking daratumumab, bortezomib, and dexamethasone (D-Vd group) reported similar changes from baseline in comparison with those taking only bortezomib and dexamethasone (Vd group). Patients received 8 cycles of treatment for the comparative study.

Patients in both groups indicated they experienced long-term improvements in quality of health and pain levels. A total of 498 patients with RRMM participated.

The researchers wrote that the study was conducted because treatment of multiple myeloma (MM) is recommended is for an undetermined amount of time (until the disease progresses) as well as because of the introduction of novel agents that have extended progression-free survival. The study was also intended to provide clinicians with further insight in treating older patients who may have comorbidities such as diabetes or cardiovascular disease.

Study results showed no clinically meaningful changes from baseline in PROs through the 8 cycles. Some patients in the Vd group saw clinically significant improvement in fatigue, pain, or sleep disturbance, but the average changes for each group were not clinically meaningful.


The authors suggested the lack of significant differences between the 2 groups may have been due to the benefit of bortezomib treatment, leaving little room for improvement from the daratumumab.

Reports continued to be collected from the D-Vd group through a maximum of 49 weeks. Improvement in quality of life and pain continued past the eighth cycle. The authors speculated those findings may have been due to a change in patients’ expectations after prolonged experience with RRMM. Less frequent visits to the clinic might have improved mood as well. Other possible reasons for the improvement included organ and skeletal recovery, which can lag other clinical responses; reduced toxicity from halting dexamethasone; and that side effects from daratumumab, unlike those of bortezomib, aren’t cumulative and stay steady over time.

PROs were measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system questionnaire (EQ-5D-5L). The EORTC QLQ-C30 is a cancer-specific questionnaire with 30 items on 5 functional scales (physical, role, emotional, cognitive, and social). The EQ-5D-5L is a generic measure of health status assessing mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. An additional scale rated “health today.”


Hungria V, Beksac M, Weisel KC, et al. Health‐related quality of life maintained over time in patients with relapsed or refractory multiple myeloma treated with daratumumab in combination with bortezomib and dexamethasone: Results from the phase III CASTOR trial. Br J Haematol. Published online February 8, 2021. doi: 10.1111/bjh.17321