Etentamig in patients with relapsed refractory amyloidosis | Rajshekhar Chakraborty, MD

Hello everyone, I am Dr. Raj Chakraborty from Columbia University Irving Medical Center. I treat multiple myeloma and lychee anamyloidosis and I'm excited to be here at the American Society of Hematology annual meeting in Orlando. And we have a lot of exciting abstracts in myeloma and anamyloidosis here this year. I am specifically excited about an abstract that I presented yesterday. It was an abstract on etantamic, which is a BCMA targeting bispecific antibody in patients with AL amyloidosis. So just for the background, bispecific antibodies, they are similar to matchmakers. So they bring the T cells or the immune cells in close proximity to the plasma cell in both multiple myeloma and amyloidosis and then it lets the T cells kill the plasma cell and that's how it works in multiple myeloma. As we know that in multiple myeloma, we have already seen really promising activity of several bispecific antibodies, which led to the FDA approval of three products thus far. And in AL amyloidosis, which is, we often say it's a cousin of myeloma and most of the treatments in amyloidosis are borrowed from myeloma. So it's obvious that these bispecific antibodies are being tested in clinical trials in amyloidosis as well. So specifically the abstract that I will talk about today is etantamic, which is a bispecific antibody being developed by AbbVie in patients with AL amyloidosis. It has a couple of unique features that I want to highlight. So first is it's given once every four weeks from the get-go. So it's very patient friendly and convenient. There is no weekly or biweekly dosing with etantamic, unlike some of the other bispecific antibodies. So that's one specific feature. And the second thing is that it has a lower affinity of binding to the T cells and hence it leads to a lower risk of having cytokine release syndrome or inflammation. So that's also very important because these patients with AL amyloidosis often have heart issues or kidney issues and they may not be able to tolerate a severe cytokine release syndrome. So what we saw in the phase one clinical trial of 34 patients is that it was overall very safe at the follow up of roughly around seven months. We did not see any treatment related deaths, which we always worry about in patients with AL amyloidosis. The risk of grade three or four infections was also very low. It was only 3%. So just compare that with the initially when these were tested in myeloma, we have seen grade three to five infection rate of 30% and now it's just 3% in AL amyloid. And the rate of CRS or cytokine release syndrome was 9% and all were very mild or grade one. So overall it was very safe and it kind of reassured all of us that bispecific antibodies will be safe to use in patients with AL amyloidosis even in those with cardiac involvement. So it was very promising to see. Now briefly on the efficacy and that's where I think we were all struck with how efficacious these products are in amyloidosis. So we saw a hematologic response of approximately 100%. So every patient responded with a very good partial response or better and about 82% of patients so far have already achieved a complete response. And that's very important because in AL amyloidosis if patients don't achieve at least a very good partial response or better quickly then those with advanced cardiac involvement may die from the disease in six to twelve months. So it's very very important for patients to achieve a very deep response rapidly and this drug is able to do that. And even more important than that is that about 40 to 50% of patients despite a short follow up have already achieved improvement in their heart and the kidney. And that's what patients really care about. They don't care so much about the numbers in the blood but they care about whether their heart is improving or their kidneys are improving and it did even with a short follow up. So we still need to wait for the phase two data but we are hoping that with these data it will be a really promising new modality of treatment in AL amyloid and maybe in the next one or two years we will get approval by the FDA so we will be able to use this drug in the real world and improve outcomes of our patients. If our videos have helped you in any way and you are able to please consider making a donation to help us continue this important work. Your gift will go three times as far when we reach $500,000 by the end of the year. Every contribution big or small makes a difference and we are deeply grateful for your support.