FIRST Trial Tops the Roster in Myeloma
FIRST Trial Tops the Roster in Myeloma
Dr. Richardson: On that note, in the relapsed/refractory setting, as we think of newer drugs, there was a lot on antibodies. What thoughts did you have from what you saw of the antibody data?
Dr. Orlowski: Let's first talk about daratumumab. If you don't mind, I'll ask you, because you have led some of the most important daratumumab studies.
Dr. Richardson: In fairness, my coinvestigators, Torben Plesner and Henk Lokhorst, have been the key leaders in the European area, and my partner, Jacob Laubach, is the lead investigator here on the US side. As a single agent, daratumumab has proven active. What Torben presented at our meeting was the first combination study with lenalidomide, and there we were seeing very robust and remarkably impressive responses very early in the trial, so it's a promising agent.
There was a nice presentation from the team looking at SAR650984, which is also a CD38-targeting antibody. It was actually Tom Martin's study presented by Joe Mikhael, and I was very impressed by that. What did you think when you saw that?
Dr. Orlowski: The data looked impressive, and the nice thing is that the 2 antibodies, even though they are both against CD38, recognize different parts of CD38.
Dr. Richardson: Exactly.
Dr. Orlowski: Although we need to prove this, it suggests the possibility that we could use one and then the other if patients are found to have disease that no longer responds to the first CD38 antibody.
Dr. Richardson: That is an extremely good point, Bob, and the piece that I found interesting is that the SAR molecule -- SAR650984 -- has a different epitope, and it doesn't rely on cross-linking in the way that daratumumab does for apoptotic signaling. I am beginning to be intrigued that some of the monoclonal antibody signal seems to be from apoptotic signaling, plus there are obviously complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and those immunologic platforms. The fact that there is this apoptotic mechanism is probably incredibly important in myeloma because we are realizing that our patients are immune-compromised, and in that context, the ability to use agents that can overdrive that immune deficiency, for want of a better term, are very important. Was there anything else in the immunology world that captured your attention beyond the antibodies?
A Look at Antibodies in Relapsed/Refractory Disease
Dr. Richardson: On that note, in the relapsed/refractory setting, as we think of newer drugs, there was a lot on antibodies. What thoughts did you have from what you saw of the antibody data?
Dr. Orlowski: Let's first talk about daratumumab. If you don't mind, I'll ask you, because you have led some of the most important daratumumab studies.
Dr. Richardson: In fairness, my coinvestigators, Torben Plesner and Henk Lokhorst, have been the key leaders in the European area, and my partner, Jacob Laubach, is the lead investigator here on the US side. As a single agent, daratumumab has proven active. What Torben presented at our meeting was the first combination study with lenalidomide, and there we were seeing very robust and remarkably impressive responses very early in the trial, so it's a promising agent.
There was a nice presentation from the team looking at SAR650984, which is also a CD38-targeting antibody. It was actually Tom Martin's study presented by Joe Mikhael, and I was very impressed by that. What did you think when you saw that?
Dr. Orlowski: The data looked impressive, and the nice thing is that the 2 antibodies, even though they are both against CD38, recognize different parts of CD38.
Dr. Richardson: Exactly.
Dr. Orlowski: Although we need to prove this, it suggests the possibility that we could use one and then the other if patients are found to have disease that no longer responds to the first CD38 antibody.
Dr. Richardson: That is an extremely good point, Bob, and the piece that I found interesting is that the SAR molecule -- SAR650984 -- has a different epitope, and it doesn't rely on cross-linking in the way that daratumumab does for apoptotic signaling. I am beginning to be intrigued that some of the monoclonal antibody signal seems to be from apoptotic signaling, plus there are obviously complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and those immunologic platforms. The fact that there is this apoptotic mechanism is probably incredibly important in myeloma because we are realizing that our patients are immune-compromised, and in that context, the ability to use agents that can overdrive that immune deficiency, for want of a better term, are very important. Was there anything else in the immunology world that captured your attention beyond the antibodies?
