EHA 2016
Daratumumab shows remarkable benefit in relapsed or refractory MM
Prof Meletios Dimopoulos - University Athens School of Medicine, Athens, Greece
Good morning. This an open label randomised phase III study of daratumumab with lenalidomide and dexamethasone, DRD, versus lenalidomide and dexamethasone, RD, in relapsed or refractory multiple myeloma, the POLLUX trial. All myeloma cells express an antigen called CD38 so this antigen was an appropriate target and we have daratumumab which is a fully human IgG monoclonal antibody that binds to CD38. With this binding daratumumab exerts several mechanisms of action: there is a direct anti-myeloma effect by inducing apoptosis, phagocytosis, activating complement, and this direct effect, we believe, is explaining the rapid action of daratumumab. On the other hand there is an effect on the immune system so daratumumab is able to activate immune cells such as CD4, CD8 positive cells and these cells attack myeloma in another way. This immune effect of daratumumab may explain the depth of response and the durability of response.
Daratumumab as a single agent has been approved by the FDA and EMEA based on a large cohort of patients who were refractory to multiple treatments and with single agent daratumumab there was a 30% response rate. The majority of these patients were heavily pre-treated, they were resistant to immunomodulatory agents, to proteasome inhibitors, and actually they had a pretty long survival.
Also daratumumab was combined with lenalidomide and dexamethasone which is a standard treatment for relapsed myeloma and in a phase II study the data were quite promising. So this prompted the POLLUX trial which included patients with relapsed or refractory myeloma. These patients had at least one prior line of therapy and they were randomised on a one to one basis to receive either the standard of care, len dex, or len dex with daratumumab. More than 600 patients were included in this trial and the primary endpoint was progression free survival with secondary endpoints being overall survival, response rate and also assessment of minimal residual disease.
This is the main finding of the study and this Kaplan-Meier curve, as you can see, indicates that there is a very significant improvement of the progression free survival in favour of daratumumab. In the control arm the median is 18.4 months, it has not been reached in the investigational arm. The hazard ratio is 0.37 which means that there is a 63% reduction in the risk of progression or death for DRD versus RD. Furthermore, there is the highest ever response rate seen in patients with relapsed or refractory myeloma, 93% of the patients achieved at least a partial response and, even more importantly, 43% of the patients achieved a complete response. This combination was well tolerated; the adverse events seen were mainly contributed to lenalidomide dexamethasone and the allergic reactions were mild and usually occurred during the first course of daratumumab.
Thus this trial shows that the combination of daratumumab with lenalidomide and dexamethasone is improving in a very dramatic way the progression free survival of the patients treated and also there is a trend for improved survival despite the short follow-up of the study. The addition of daratumumab to lenalidomide and dexamethasone induces deep and durable responses and data with minimal residual disease indicates that we can achieve a minimal residual disease negativity status in a significant number of patients. Thus the combination of daratumumab with lenalidomide and dexamethasone potentially is representing a new standard of care for relapsed or refractory myeloma patients with one prior treatment. Thank you very much.
