Relapsed/Refractory Multiple Myeloma: BCMA Targeted Bispecifics

In part 2 of Docwire News’ roundtable series discussing Relapsed/Refractory Multiple Myeloma, moderator Dr. Saad Usmani and Dr. Cesar Rodriguez discuss research presented at ASH 2021 on bispecifics. In this video, Cesar Rodriguez talks about data presented on BCMA targeted bispecifics, including Teclistamab, Regeneron 5458, and more.

Saad Usmani: Cesar, bispecifics were the big rage, man?

Cesar Rodriguez: It were. There were a lot of presentations on bispecifics. The most common, obviously, BCMA targeted bispecifics. There were four different presentations. Teclistamab, which is I think the one that’s most advanced, presented data on single agent with weekly and every other week dosing Sub-Q and IV. Their overall response rates are very promising, 65% overall response rates, 77% of these patients were triple refractory. And the degree of CRS, even though we see it in two thirds of the patients, it’s just grade one and two, which is relatively manageable.

The other agents that were BCMA were Regeneron 5458, they also had overall response rates around the same line. 73% with all of the patients who were in this study, were triple-class refractory. CRS were 38%, they did different step of dosing for this clinical trial. Erlotinib was another BCMA. This was a weekly Sub-Q dosing. And overall response rates for this was 70%. 80% of the patients, that’s CRS, also just grade one and two, there were no —

And then teneobio, TNB-383b or I think now it’s called AbbVie-383b. It is unique in its class because it’s once every three weeks unlike the other agents that are weekly or every other week. And the response rates were also very impressive at that therapeutic doses of 40 to 60 milligrams. But, 60% overall response rates and very low CRS with negligible grade three and four CRS. So all of these are very good. We are obviously not seeing a flattening of the curve, so what trying to play with it and combining with other agents? So they did present teclistamab in combination with daratumumab, showing an overall response rate of 78%, which is slightly improved over single agent. And there’s an ongoing study with daratumumab and pomalidomide, which hopefully we’ll hear data in the near future.

But erlotinib was another agent that was combined with EMITs only for patients in each arm, but they combine it with lenalidomide for patients and for patients with pomalidomide. I don’t have response rates on that because it’s such a small population, but it just shows us that we’re starting to see combination therapy and see if this improves response without actually worsening or increasing toxicity. And then non-BCMA targets is the other thing, or how can we do something a little bit different. So there’s the GPRC5D, talquetamab, which was presented, which also showed very interesting results and very good overall response rates as well, as it showed for people who were—77% of the patients were triple-class refractory, and 70% overall response rate was very good. And out of these patients, out of 95 patients, 30% of the patients had prior BCMA exposure, which is pretty good, and also shows how sequencing could be an option.

In combination with their daratumumab was also presented with 80% overall response rates. Anti-FcRH5, cevostamab was also presented, and they had an overall response rate of 37. Out of 160 patients that they had, 33% were prior BCMA exposure. And of those patients, 44% had an overall response rate. So we are seeing responses with our subsidy rates varying between different target modality, but CRS levels are very manageable with all of the bispecifics. And now we’re starting to see trispecifics where we might be targeting BCMA, but we’re trying to find a third target to try to either increase the half-life of the agent. So one of the presentations included trispecific with BCMA and CD3, and also targeting albumin, so they combined albumin to keep a longer half-life, and hopefully we won’t have to be dosing as frequently. So it’s interesting what we’re seeing going forward. Hopefully, we’ll be seeing more trispecifics at our next ASH.

Saad Usmani: Yeah, I think we are probably going to have more sessions on these bispecifics and combinations. I think I was impressed with the dara combinations with teclistamab, particularly because more than half of those patients were actually dara refractory. So I think that immunomodulatory function of dara was kicking in, in combination with the bispecific there.