How is amyloidosis treated? What drugs are used?

00:00:08:16 - 00:00:10:07
 
How is amyloidosis treated?

00:00:11:07 - 00:00:14:09
 
So the drugs that we used to treat light chain amyloidosis

00:00:14:09 - 00:00:16:15
 
most of them are barred from multiple myeloma.

00:00:16:15 - 00:00:23:03
 
And that until about a month and a half ago, so March of 2021. There were no drugs approved

00:00:23:03 - 00:00:24:11
 
for treating amyloidosis.

00:00:24:11 - 00:00:33:23
 
But we know that most drugs that we use in multiple myeloma should work in amyloidosis. Also, again, because it all boils down to these sick plasma cells in the bone marrow.

00:00:33:23 - 00:00:39:14
 
but as of a month and a half ago, the daratumumab medication was now approved for treating amyloidosis.

00:00:39:14 - 00:00:57:07
 
So that drug is now again first drug that's been approved for treating amyloidosis. That's great. We use that one quite a bit. And then otherwise we still borrow a lot of drugs from multiple myeloma. So a lot of the same drugs that we use for treating multiple myeloma we use in amyloidosis and slightly different combinations and doses, but it's a lot of the same drugs.

00:00:57:09 - 00:01:05:01
 
So all the same drug classes, proteasome inhibitors, immunomodulatory agents, the monoclonal antibodies, all the rest, and even stem cell transplant

00:01:05:10 - 00:01:07:22
 
What is the most common treatment for amyloidosis?

00:01:09:02 - 00:01:35:05
 
There are many types of amyloid, but al amyloidosis or the closely related subtype ah amyloidosis, both of which are clonal. Plasma cell diseases like multiple myeloma are typically treated with the therapies that we've developed for multiple myeloma because those clonal plasma cells are susceptible to these therapies, just like myeloma, plasma cells are susceptible to them.

00:01:35:05 - 00:01:36:01
 
we actually

00:01:36:00 - 00:01:59:02
 
commonly use myeloma regimens to treat al amyloidosis CyBorD, which is the combination of cyclophosphamide bortezomib and dexamethasone is probably the most commonly used regimen in the United States. A similar regimen of melphalan, bortezomib and dexamethasone is used a bit more commonly in Europe,

00:01:59:01 - 00:02:05:05
 
and more recently there's been some great data about using the monoclonal antibody daratumumab to treat

00:02:05:04 - 00:02:09:13
 
al amyloidosis with really nice efficacy.

00:02:09:12 - 00:02:19:18
 
When we use myeloma therapies to treat amyloid though, because of the way amyloid can affect patients organs, particularly the heart and the kidneys,

00:02:19:18 - 00:02:27:16
 
sometimes the doses or the intensity of the therapy needs to be reduced to make it more tolerable for amyloid patients.

00:02:28:04 - 00:02:30:04
 
What drugs are used to treat amyloidosis?

00:02:31:17 - 00:02:48:19
 
all types of amyloidosis are treated completely differently. And a lot of that has to do with where it comes from. One of the interesting things about amyloidosis is that it's almost a convergence of different disease processes and in the same organs. And what I mean by that is that when people have amyloidosis,

00:02:48:19 - 00:02:54:00
 
the problem is that this abnormal protein deposits in the different organs such as let's say the heart,

00:02:53:23 - 00:02:58:18
 
but in different people, that amyloidosis can come from different places, different sources.

00:02:58:18 - 00:03:14:02
 
And so in light chain amyloidosis, the problem is plasma cells in the bone marrow that are sick and they're proliferating too much and they're making abnormal proteins that deposit in different organs that then form the amyloidosis, and that's the light chain protein.

00:03:14:02 - 00:03:23:23
 
Conversely, when people have TTR amyloidosis, that protein actually comes from the liver. It's the liver making what's usually a normal form of this protein called TTR.

00:03:24:01 - 00:03:26:12
 
There are mutant versions of this also, but

00:03:26:12 - 00:03:39:13
 
primarily normal TTR and that protein then deposits in different organs and causes them to have trouble functioning. And so completely different sources of the problem. But in all of them, they converge in these different organs

00:03:39:12 - 00:03:42:16
 
where the protein deposits and causes amyloidosis.

00:03:42:16 - 00:03:46:23
 
the treatment strategies mimic those of multiple myeloma?

00:03:46:23 - 00:03:51:08
 
Because again, the the cell of origin is similar.

00:03:51:08 - 00:04:23:18
 
but the one thing that must be recognized in the community is that the pathophysiology, even though in the cell of origin is similar, the pathophysiology in the patients is different, so that patients with amyloid tolerate treatments very differently than does a myeloma patient. I would say amyloid patients are often more frail and subject to toxicity because they have heart failure or

00:04:23:18 - 00:04:28:19
 
low albumin or kidney dysfunction that

00:04:28:19 - 00:04:31:22
 
makes them sensitive to treatments.

00:04:32:00 - 00:04:38:19
 
But if we say what are the standard treatments for patients with with amyloidosis,

00:04:38:19 - 00:04:44:05
 
the mainstay used to be high dose, melphalan

00:04:44:05 - 00:04:49:06
 
and stem cell transplant when we didn't have any available drugs

00:04:49:06 - 00:04:50:14
 
and actually

00:04:50:14 - 00:05:04:14
 
about 30% of patients can go into remission with this treatment and then not require additional therapy. Distinct from multiple myeloma patients. If you go into remission

00:05:04:14 - 00:05:09:12
 
or complete remission, if you have amyloidosis and you go into complete remission

00:05:09:12 - 00:05:13:20
 
there, you often can have a durable response

00:05:13:20 - 00:05:16:12
 
for upwards of decades.

00:05:16:12 - 00:05:34:14
 
But there was more toxicity with high dose chemotherapy compared to multiple myeloma and really Velcade or Bortezomib has become a new standard since it's been developed because

00:05:34:14 - 00:05:44:19
 
in the US Velcade plus cytokine and dexamethasone, the CyBorD regimen has great efficacy

00:05:44:19 - 00:05:47:13
 
in the ex-U.S..

00:05:47:13 - 00:05:51:19
 
The combination of Velcade, melphalan and

00:05:51:19 - 00:05:56:03
 
and dexamethasone is really the standard of care.

00:05:56:03 - 00:05:57:04
 
I would say.

00:05:57:04 - 00:06:15:17
 
there's excitement around the novel antibodies in multiple myeloma. It also seems that patients with amyloidosis have exquisite sensitivity to the antibodies. Daratumumab or isatuxumab and those studies are ongoing.

00:06:15:17 - 00:06:25:06
 
And a phase three trial is is currently enrolling with CyBorD plus minus daratumumab in the first line setting.

00:06:25:12 - 00:06:34:00

00:06:34:00 - 00:06:41:14