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Daratumumab Continues To Show Promise For Relapsed/Refractory Myeloma Patients (ASH 2012)

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Published: Jan 9, 2013 12:37 pm

Daratumumab continues to show promise for relapsed and refractory multiple myeloma patients. Results from a Phase 1/2 study indicate that daratumumab may be effective and safe in heavily pretreated patients.

In particular, daratumumab's activity as an anti-myeloma agent seems at least as good as that of the newest myeloma therapies.

“The response to daratumumab was accompanied by the clearance of myeloma cells,” said Dr. Torben Plesner from the Vejle Hospital in Denmark, who presented the findings from the daratumumab trial at the 2012 American Society of Hematology (ASH) meeting last month.

“Daratumumab has shown a favorable safety profile as a [single-agent therapy],” he added.

However, Dr. Plesner noted that the maximum tolerated dose of daratumumab had not been reached yet, and further trials are needed to assess its effectiveness in combination with other drugs.

Daratumumab is being developed by the Danish pharmaceutical company Genmab together with Janssen Biotech, a Johnson & Johnson (NYSE: JNJ) subsidiary.  The medicine is a monoclonal antibody, a class of drugs that includes two other potential new myeloma treatments, elotuzumab and siltuximab.

Daratumumab binds to the CD38 molecule, which is found on the surface of multiple myeloma and other blood cancer cells.  Once daratumumab is bound to the CD38 molecule on cancer cells, it signals for the immune system to kill the cells.

Initial results of the current trial, which Dr. Plesner presented at the American Society of Clinical Oncology Meeting in June 2012, showed that 24 percent of patients had achieved a partial response to daratumumab (see related Beacon news).

The updated findings that Dr. Plesner presented at ASH were based on data from 32 heavily pretreated myeloma patients who were ineligible for stem cell transplantation. Patients had received a median of six prior therapies. The median patient age was 61 years.

All patients had previously been treated with Velcade (bortezomib), and 90 percent of patients had also received Revlimid (lenalidomide).

Patients received varying doses of daratumumab, ranging from 0.005 mg/kg up to 24 mg/kg for eight weeks.

Overall, 47 percent of the patients experienced a reduction in M-protein levels in the blood or urine, which corresponded to the following response rates: 12.5 percent of patients achieved a partial response, 19 percent a minor response, and 16 percent stable disease,

Dr. Plesner emphasized that daratumumab was more effective at lowering M-protein levels when administered at higher doses.

“At doses of 4 mg/kg and above, 67 percent of patients had a least a minimal response,” he explained.

Dr. Plesner added that “the progression-free survival also increased with longer exposure to daratumumab.”

Daratumumab's activity against myeloma in this early-stage trial compares favorably with what was observed in the initial dose-ranging trials for Kyprolis (carfilzomib), the most recently approved anti-myeloma therapy.

In the part of the Kyprolis trial (results; PDF) using the drug's current dosing schedule, a slightly higher share of the relevant patients (17 percent versus 12.5 percent for daratumumab) achieved a partial response.  However, more patients in the daratumumab trial (47 percent versus 38 percent for Kyprolis) experienced stable disease or better.

Moreover, the patients in the Kyprolis trial were not quite as heavily pretreated as those in the daratumumab trial.

According to Dr. Plesner, daratumumab also has demonstrated a favorable safety profile in its trial. “Daratumumab was surprisingly well tolerated,” he said during his ASH presentation.

Most of daratumumab's side effects were infusion-related, occurring within three to four hours of the infusion.

The most commonly observed severe side effects included difficulty breathing (3 percent), low blood cell counts (3 percent), and elevated liver enzymes (3 percent).

Going forward, Dr. Plesner and his colleagues plan to study the 8 mg/kg dose of daratumumab as a single-agent therapy and in combination with other drugs.

For more information, please refer to abstract 73 on the ASH 2012 meeting website, as well as Dr. Plesner’s presentation slides, which he has made available for download and viewing as a courtesy to the Beacon’s readers. For more information regarding clinical trials studying daratumumab, please visit the clinicaltrials.gov website.

Photo by IndyDina with Mr. Wonderful on Flickr - some rights reserved.
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  • nancy shamanna said:

    Thanks for the two articles this week about antibody therapy. The two drugs, Lorvotuzumab and Daratumab sound as if they are effective. The lorvotuzumab drug was used on patients who showed the marker on Myeloma cells, CD56, whereas the Daratumab worked on the CD38 marker. Lorvotuzumab was an 'antibody-drug' conjugate (ADC)...was the Daratumab also an ADC?

    It is interesting that these new antibodies were grown in mice first. Can you elaborate as to how they could be made for 'mass production'?

    One last question...do all myeloma patiients show both the CD56 and the CD38 proteins on the myeloma cell coats?

    Thanks Maike and Navneet for this. Also, the slide presentations were very good...they help one to visualize how the research project was done. As a novice reader, I find them to be helpful.