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Wave of Therapies Being Developed in AL Amyloidosis Space

Gina Columbus
Published: Wednesday, Jan 24, 2018

Sandy W. Wong, MD
Sandy W. Wong, MD
Immunoglobulin light chain amyloidosis (AL amyloidosis), known as the most common form of systemic amyloidosis and associated with an underlying plasma cell dyscrasia, is frequently difficult to recognize because it presents similarly to a variety of other hematologic disorders.

However, explains Sandy W. Wong, MD, therapeutic developments for AL amyloidosis have recently been emerging to include plasma cell treatment and anti-amyloid fibril therapy to propel this field into a more positive direction.

For example, a prospective phase II study presented during the 2017 ASH Annual Meeting showed that the CD38-directed monoclonal antibody daratumumab (Darzalex) was found to induce deep and rapid hematological responses in pretreated patients with AL amyloidosis.1 Among 24 evaluable patients, the hematologic complete response rate was 17%, 29% experienced a very good partial response, and 17% achieved a partial response. The overall response rate was 63%. 

There have also been early-phase studies with anti-amyloid fibril therapy. NEOD001, a monoclonal antibody, was well tolerated in a first-in-human study of 27 patients with AL amyloidosis. Of 14 cardiac-evaluable patients, 8 (57%) met the criteria for cardiac response and 6 (43%) had stable disease. Of 15 renal-evaluable patients, 9 (60%) met the criteria for renal response and 6 patients (40%) had stable disease.2

In an interview during the 2017 OncLive® State of the Science SummitTM on Hematologic Malignancies, Wong, an assistant clinical professor in the Division of Hematology/Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, discussed some of these therapeutic advancements and recent data that have shown excitement in this landscape.

OncLive: What developments have we recently seen in this field?

Wong: The developments have basically been separated into 2 major categories. One is anti-plasma cell therapy and the other one is anti-amyloid fibril therapy. In terms of the anti-plasma therapies, the new development has been the publication of the phase I trial for ixazomib in AL amyloidosis. It looks to be quite an active drug with a relatively good safety profile.

The other drug that has also made its headlines in AL amyloidosis has also been pomalidomide (Pomalyst). That trial was also published this year. It does also have a good safety profile as well as a good efficacy profile. The anti-plasma cell therapies have really made the splash.

The most prominent one that garnered a lot of people’s attention is daratumumab. There were early reports of [using] daratumumab in this disease; the first report was published early last year by Dr Morie A. Gertz. He presented 2 cases in his paper that was published in Blood. Earlier [in 2017], there was a retrospective study looking at the response rates of daratumumab, which were very impressive.

Most recently, at the 2017 ASH Annual Meeting, there were actually 2 prospective trials that were presented in an oral session, as well as 2 retrospective studies in poster form that also showed the preliminary safety profile of daratumumab and preliminary efficacy profiles. It is a very exciting time. We have 3 drugs that have made an initial splash in the world of AL amyloidosis in terms of plasma cell therapy.

The other class of agents include the anti-amyloid fibril treatments, and none of these are FDA approved yet. One of them that has been published is NEOD001, which is a drug that is an anti-amyloid fibril monoclonal antibody against the amyloid fibrosis themselves in an effort to clean up the amyloid deposits in the body to allow organ recovery. That antibody is very interesting because the first paper that was published was in the Journal of Clinical Oncology a couple of years ago as a phase I trial; it looks like it is very safe to give. Preliminary [findings show that] there does seem to be cardiac, renal, and neurologic responses to that drug, so that is really exciting.

The other anti-amyloid fibril therapy is 111F4. Now, it has been renamed to CAEL-101 and that was actually presented at the 2017 ASH Annual Meeting. It was a final analysis of the phase I study with this drug and looks similar to NEOD001; it looks quite safe and there are preliminary signals of efficacy, which are very exciting.  


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