Myeloma Morning: Positive Darzalex & Aplidin Trial Results, And The FDA Approves Defitelio

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
- Amodio, N. et al., “Therapeutic targeting of miR-29b/HDAC4 epigenetic loop in multiple myeloma” in Molecular Cancer Therapeutics, March 28, 2016 (abstract)
- 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)
Myeloma Morning is a comprehensive daily review of multiple myeloma research and news.
Each edition of Myeloma Morning is compiled by The Beacon after a thorough search of publication databases and mainstream news sources. This search leads to the list of new myeloma-related research articles included at the bottom of every Myeloma Morning.
The top part of Myeloma Morning highlights and summarizes selected articles from the day's list of new publications. It also discusses any myeloma-related business or regulatory developments that have occurred.
This two-part structure to Myeloma Morning makes it a perfect way to stay current on all myeloma-related research and news.
If you are a researcher, you can help The Beacon inform the multiple myeloma community of your work. When you and your colleagues publish a new study, feel free to email a copy of it to us shortly before (or shortly after) it is published. If you wish, include with your email any background or explanatory information you believe may help us if we decide to summarize your article for our readers. Our email address is , and we respect embargo requests.
Related Articles:
- Two Darzalex Clinical Trials Halted; Little Impact Expected On Drug’s Use In Multiple Myeloma
- Darzalex May Affect Different Uninvolved Immunoglobulins Differently
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- FDA Approves Once-Weekly Dosing And Revised Safety Information For Kyprolis
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
I appreciate the Myeloma Morning briefs very much. Thank you, Boris. Thumbs up on the Darzalex trial results. I hadn't heard of VOD, interesting and scary. Sea squirts, who knew? This Myeloma Morning format works great for me as a patient not currently facing major issues, but who wants to keep up with breaking multiple myeloma info. Thanks, again.