Good morning, myeloma world.

We all should have seen this coming.

After days and days of having no major myeloma business news to cover here at Myeloma Morning, what hap­pens? Suddenly, there's not just one new myeloma-related business devel­op­ment to discuss. And not just two. But a full three such news items to review.

So let's start with those devel­op­ments, after which we'll take a quick look at a new research article and what's been going on in the Beacon's forum.

Initial Results Of Darzalex MMY3004 Clinical Trial

We use the phrase “myeloma-related business news” loosely here at Myeloma Morning. Sometimes, it really is business news. But mainly it's just news based on com­pany press releases rather than peer-reviewed journal articles.

Our first “business” news item is a perfect example: Johnson & Johnson reported yesterday that Darzalex (dara­tu­mu­mab) was suc­cess­ful in an im­por­tant Phase 3 clin­i­cal trial (press release).

The MMY3004 (CASTOR) trial is com­par­ing the efficacy and safety of Darzalex com­bined with Velcade (bor­tez­o­mib) and dexa­meth­a­sone (DVd) to Velcade and dexa­meth­a­sone alone (Vd). There are 490 re­lapsed or refractory multiple myeloma patients enrolled in the trial at treat­ment centers across the globe. Each patient was ran­domly assigned to be treated with either DVd or Vd.

At a planned interim review of the trial results, an independent monitoring committee de­ter­mined that patients being treated with DVd have sig­nif­i­cantly longer pro­gres­sion-free survival than patients on Vd. The im­prove­ment is sig­nif­i­cant enough that the monitoring committee de­ter­mined that it is no longer nec­es­sary for further patients to be enrolled in the trial. Existing trial par­tic­i­pants, how­ever, will con­tinue to be monitored to track treat­ment efficacy and safety.

We asked Beacon Medical Advisor Dr. Kenneth Shain of the Moffitt Cancer Center in Tampa, Florida for his thoughts on the Darzalex news. He noted that earlier studies have shown that Darzalex works well com­bined with dexa­meth­a­sone and the immuno­modu­la­tory agent Revlimid (lena­lido­mide). Thus, the news that Darzalex also seems to combine well with Velcade, a drug in the pro­te­a­some inhibitor class of ther­a­pies, “is outstanding, as it opens up a lot of exciting oppor­tu­ni­ties for com­bi­na­tion ther­apy,” said Dr. Shain.

But Dr. Shain had more to say about Darzalex and the new trial results, and we think it's worth sharing his extended feedback with Myeloma Morning readers. He said:

"I personally believe that Darzalex has the poten­tial to be one of the most influential new ther­a­pies in multiple myeloma. The novel multiple myeloma-specific anti­body ther­a­pies – Darzalex, Empliciti (elotuzumab), and those to come – have the poten­tial to provide marked changes in the out­comes for our patients. Darzalex, specifically, has garnered a great deal of excitement, as we have already seen its single agent activity in highly re­lapsed patient pop­u­la­tions, leading to its Food and Drug Admin­is­tra­tion approval. Further, early-stage trial results have created a great deal of antic­i­pa­tion in the myeloma com­munity for Darzalex as a critical addi­tion to both pro­te­a­some inhibitor and immuno­modu­latory agent-based com­bi­na­tions in re­lapsed / refractory multiple myeloma.

"The results from the pre-planned interim analysis of the Phase 3 MMY3004 (CASTOR) study looking at the addi­tion of Darzalex to Velcade and dexa­meth­a­sone (Vd) rel­a­tive­ to Vd alone val­i­date that ex­pec­ta­tion in a large number of patients (490). Further highlighting the clin­i­cal sig­nif­i­cance of the results from this interim analysis, the independent data monitoring committee has rec­om­mended halting the study sec­ond­ary to the pos­i­tive ad­van­tage. We antic­i­pate the presentation of these results and translation of this into the care of our multiple myeloma patients."

Initial Results Of Aplidin ADMYRE Phase 3 Trial

Our next business news item is about results of another inter­na­tional clin­i­cal trial. The Spanish com­pany PharmaMar earlier today reported pos­i­tive results from a key Phase 3 trial testing Aplidin (plitidepsin) as a poten­tial treat­ment for re­lapsed multiple myeloma patients (press release).

Aplidin is a poten­tial new myeloma ther­apy that has been under devel­op­ment for a while, but not many people seem to know about it. Its active ingredient is derived from a species of marine animals known as ascidians, or “sea squirts.”

Early trials testing Aplidin as a single agent suggested the drug might not have very much anti-myeloma activity by itself. In the new trial, how­ever, the drug is being tested in com­bi­na­tion with dexa­meth­a­sone, with some patients being treated with that two-drug, Aplidin-dexamethasone com­bi­na­tion, and others receiving just dexa­meth­a­sone.

A total of 255 patients have enrolled in the ran­dom­ized, inter­na­tional Phase 3 trial called ADMYRE. Patients in the trial had re­lapsed or re­lapsed and refractory multiple myeloma with at least three, but not more than six, prior treat­ment regi­mens.

The news reported today is that patients in the trial who were treated with Aplidin and dexa­meth­a­sone had a statistically sig­nif­i­cant 35 per­cent lower risk of disease pro­gres­sion or death.

Based on these results, PharmaMar says that it will submit an appli­ca­tion later this year to have Aplidin approved as a new myeloma treat­ment in Europe. Plans also are underway through a PharmaMar business partner to seek approval of Aplidin in a number of Asian countries and in Australia and New Zealand. There is no news at this point, how­ever, on plans for a sub­mission for U.S. regu­la­tory approval.

FDA Approval For Defitelio

The United States Food and Drug Admin­istra­tion (FDA) yesterday announced that it has approved Defitelio (defibrotide) to treat a rare com­pli­ca­tion of stem cell trans­plan­ta­tion (FDA press release, Defitelio U.S. prescribing in­for­ma­tion).

In particular, Defitelio is approved for the treat­ment of liver-related veno-occlusive disease (VOD), a stem cell trans­plant com­pli­ca­tion that is rare, but can lead to liver failure and death in patients who develop it.

Now, many Myeloma Morning readers are probably thinking, “Okay, I need to know about Defitelio's approval because many myeloma patients have stem cell trans­plants, and Defitelio can be used to treat a rare trans­plant-related com­pli­ca­tion.”

That's true. But there's more.

Defitelio, it turns out, was once tested as a poten­tial treat­ment for multiple myeloma. See, for example, this journal article reporting results of a trial testing Defitelio com­bined with mel­phalan, pred­ni­sone, and thalido­mide (Thalomid) in re­lapsed myeloma patients (related Beacon news article).

So, given the research that's been done to in­ves­ti­gate Defitelio as a myeloma ther­apy, it would be fair to ask: will it be used “off label” (that is, for an unapproved use) to treat myeloma patients?

We asked Beacon Medical Advisor Dr. Heather Landau exactly this question. Dr. Landau is a myeloma specialist at Memorial Sloan Kettering Cancer Center in New York City.

Dr. Landau noted that Defitelio “has a very specific role in VOD and is effective in that regard; but it also has toxicity and indeed is not benign.” She also ex­pec­ts the price of Defitelio to be sizable, given the niche role of the drug.

These factors, com­bined with the recent approval of several new ther­a­pies for multiple myeloma, lead Dr. Landau to ex­pec­t that there will not be much off label use of Defitelio to treat multiple myeloma.

New Research Studies, And Forum Highlights

We list two items in the list of new myeloma research studies in­cluded at the end of this article.  We'll focus here on one of the new studies, which discusses the poten­tial new myeloma ther­apy PAT-SM6, a naturally occuring human anti­body under devel­op­ment by the Australian com­pany Patrys (abstract).

The new study primarily reports pre­clin­i­cal (laboratory) in­ves­ti­ga­tions of PAT-SM6 in com­bi­na­tion with Revlimid, Velcade, and dexa­meth­a­sone. It also in­cludes a single case report for a re­lapsed multiple myeloma patient who was treated with PAT-SM6 in com­bi­na­tion with Revlimid and Velcade.

Finally, there's still plenty of activity in the Beacon forum these days, and lots of forum regulars who do a great job providing sup­port and assistance to fellow patients and care­givers. Here are two quick highlights:

• Brenda introduced herself and the story of her multiple myeloma diagnosis, which was sparked by her doctor noticing a low white blood cell count (link to discussion)
• Debbie shared a more detailed update about Day +12 of her autologous stem cell transplant (link to update).

New Myeloma-Related Research Articles

1. Amodio, N. et al., “Therapeutic targeting of miR-29b/HDAC4 epigenetic loop in multiple myeloma” in Molecular Cancer Therapeutics, March 28, 2016 (abstract)
2. Rasche, L. et al., “A GRP78-directed monoclonal antibody recaptures response in refractory multiple myeloma with extramedullary involvement” in Clinical Cancer Research, March 30, 2016 (abstract)