Daratumumab belongs to a new class of drugs called anti-CD38 monoclonal antibodies. Daratumumab targets the myeloma cells by binding to an antigen, CD38, expressed on the surface of the plasma cells. Daratumumab single agent has shown to be effective in relapsed and refractory myeloma patients and according to these results the main objective of this phase Ib trial has been to combine this monoclonal antibody, daratumumab, with different backbone regimes commonly used for the management of multiple myeloma patients. The backbone treatments chosen for this trial were bortezomib plus dexamethasone, bortezomib plus melphalan plus prednisone, two regimes commonly used in the up-front setting of non-transplant candidates, VTD – bortezomib, thalidomide plus dexamethasone, a regime commonly used as induction prior to autologous stem cell transplant, and finally pomalidomide plus dexamethasone, but in the setting of relapsed and refractory myeloma patients.
Here you can see the baseline characteristics of the patients and, as I mentioned, the median age is more than 70 years for VD and VMP, 57 for VTD plus dara and 62 years for pom-dex plus daratumumab. The median exposition to daratumumab, the median number of infusions, ranged between eight and twelve and concerning the disposition I think it’s important to note that there were four discontinuations of the treatment. But you can see here as these four or five subjects electively taken off the study to proceed to autologous stem cell transplant and just three patients discontinued in the pom-dex-dara, two of them due to progression, another due to investigator criteria.
Here you can see the safety profile of daratumumab plus the different backbone treatments and to note that there were some serious adverse events but most of them related to the backbone therapy and just one daratumumab related serious adverse event consisting of a laboratory testing interference. The other haematological and non-haematological toxicities were consistent with the toxicity reported prior with the backbones VD, VMP, VTD or pomalidomide plus dexamethasone. Just a few infusion related reactions concerning daratumumab related safety profile but most of them were of grade 1 and 2 and they occurred during the first infusions.
Here you can see the efficacy. If we focus on the VD, VMP and VTD regimes used in the up-front settings in patients newly diagnosed, 100% of the patients responded to this combination including partial response and some patients in very good partial response. If we focus on the pomalidomide plus dexamethasone plus daratumumab, remember a combination used in patients in relapsed and refractory disease, again 50% of the patients responded to this combination and I would like to note that even one patient achieved a stringent complete remission.
Here you can see in a graph the maximal percentage change in the paraprotein from baseline and you can see here as most patients reduced their monoclonal component during the treatment with daratumumab plus the different backbone treatments.
The median time to first response was rapid and this is consistent with what we have previously observed with the different backbone treatments.
In summary, we consider that the addition of 16mg/kg of daratumumab to the various backbones was well tolerated in all evaluable patients and did not result in significant additional toxicity. Finally, daratumumab was associated with high rates of response in combination with the different backbones, Velcade dexamethasone, Velcade melphalan plus prednisone, Velcade thalidomide and dexamethasone and pomalidomide plus dexamethasone.