Daratumumab in the News Again: Showing Benefit in Frontline and at Relapse

On August 24th, Genmab announced that the ALCYONE trial, which compared the combination of daratumumab (Darzalex®) with VMP (Velcade®/melphalan/prednisone) to VMP alone, hit the primary endpoint for treatment of myeloma as a frontline therapy. The progression-free survival (PFS) for the VMP alone was 18.1 months versus “not reached” with the addition of daratumumab. Showing the added value of daratumumab is very important in Europe, where VMP is a standard frontline regimen.

Summer Updates: More about “dara” …and ideas about what may cause myeloma

In an important paper published recently in the journal Blood, researchers from the Netherlands and Belgium correlate the response to daratumumab (dara), the anti-CD38 monoclonal antibody, to the level of CD38 expression on the myeloma cells and whether or not complement inhibitory proteins (CIPs) CD55 and CD59 emerge with treatment. A separate report in Blood from a joint Danish, Netherlands, Italian, and US team summarizes the findings of a phase I/ II study combining dara with lenalidomide + dexamethasone to show that the combination produces responses in 81% of patients versus approximately 30% with dara alone. These results led to the development of the POLLUX trial, which recently confirmed the approximately 80% response rate for the combo with 78% of patients still in remission at close to 2 years. The results of the combination of dara with bortezomib (Velcade®) and dexamethasone (the CASTOR trial) were reported at ASCO in June this year and have just been published in the New England Journal of Medicine. In this case, the response rate was 82.9% but with shorter follow-up thus far. 

Darzalex® (daratumumab): more very good news and a caution

Janssen’s Darzalex®, or daratumumab, has been granted “Breakthrough Therapy” designation by the US Food and Drug Administration for use in combination with Revlimid® (lenalidomide) and dexamethasone, and Velcade® (bortezomib) and dexamethasone, for the treatment of multiple myeloma patients who have received at least one previous therapy. The designation was based on data from the CASTOR and POLLUX trials recently presented at ASCO 2016 and EHA 2016 respectively. The prolongation of remissions achieved by combining Darzalex with either Velcade/dex or Revlimid/dex were highlighted in my Myeloma Updates 2016 presentation, as well as recent blogs, “ASCO 2016: More excitement about daratumumab (Darzalex®), and tremendous interest in value and costs” and “Preview of the Black Swan Research Initiative’s First US Cure Trial.”

ASCO 2016: More excitement about daratumumab (Darzalex®), and tremendous interest in value and costs

As usual, far fewer myeloma-related abstracts will be presented at this year’s meeting of the American Society of Clinical Oncology (ASCO) than are presented at the annual meeting of the American Society of Hematology (ASH) each December.  However, there is quite a bit of excitement about the results of the phase III CASTOR study to be presented at the Plenary session on Sunday, June 5. This randomized trial compares daratumumab plus bortezomib (Velcade® - [V])/ dexamethasone [d] versus Vd alone. Since this is a “late-breaking” plenary abstract, the abstract is not being released until Sunday, June 5th at 7:30 am (EDT). However, the positive interim results were provided in a press release on March 30, 2016. Beyond this abstract, the other interesting aspect of this year’s ASCO meeting is

Three early Christmas presents… but what will be the New Year’s resolutions?

November was an amazing month for the myeloma community: FDA approval for three new therapies. The very good, but challenging problem is how to integrate and use these three new agents within the recommended treatment protocols for myeloma patients.

First monoclonal antibody approved