Updates on melflufen show that it may kill Velcade-resistant cells and reduce bone-related issues, according to two new studies.
The Myeloma Crowd by HealthTree has recently published several articles relating to the recently approved anti-myeloma drug Pepaxto (melflufen or melphalan flufenamide, developed by the Swedish company Oncopeptides), a first-in-class peptide-drug conjugate. To learn more about this drug you may wish to refer to this prior article. Apart from three clinical updates that were presented at the most recent ASCO forum, there are two very recent publications in peer reviewed journals that are also interesting to be aware of.
The journal Hemasphere published a study that indicates that melflufen eradicates Velcade (bortezomib) resistant myeloma cells and their tumor initiating precursors. The key points of this study are:
This study showed that drugs that most of us are familiar with, specifically dexamethasone, Revlimid, Velcade and cyclophosphamide, have only a limited effect on eradicating these early myeloma progenitor cells.
More advanced drugs such as Kyprolis, iberdomide (a new drug in the Bristol-Myers pipeline), CC-29480 (a Bristol-Myers CelMOD agent currently in clinical trials, and the fairly recently approved drug Xpovio (Karyopharm’s selenixor), ARE active in suppressing the growth of clones from precursor cells, but not with 100% efficiency.
Melphalan (another drug that those of us who have had auto stem cell transplants, are familiar with) IS 100 % active, but only at very high doses. Melflufen has shown the same effect (100 % efficiency) at concentrations 100-fold lower [than melphalan]. [emphasis added]
Oncopeptides (the company that developed melflufen and that recently secured full FDA approval) has recently reported several studies where triplets that included melflufen had positive outcomes. For example: ‘The daratumumab/melflufen/dexamethasone arm of the ANCHOR study have shown overall response rate of 76% and clinical benefit rate of 79%.’
The journal Bone Reports published a study that indicates that melflufen may have beneficial effects of reducing myeloma bone related problems. The key points of this study are:
These results demonstrate that melflufen may exert beneficial effects in patients with multiple myeloma such as reducing bone resorption and immunosuppressive milieu by inhibiting osteoclastogenesis. [emphasis added]
Both of the above referenced papers are not the easiest to read or digest but I will still encourage you to try as they are full of interesting ‘stuff’ to learn and know about with respect to our disease and I commend Oncopeptides for digging deep into the mechanisms of action of melflufen. The better understanding of the compound will provide for better, targeted use in the future.
about the author
I am a patient diagnosed in 2014 with primary plasma cell leukemia (pPCL), a rare and aggressive variant of multiple myeloma and have been very fortunate to find successful treatment at the division of Cellular Therapy at the Duke University Cancer Institute. My wife, Vicki, and I have two adult children and two grandsons who are the ‘lights of our lives’. Successful treatment has allowed Vicki and I to do what we love best : traveling the world, albeit it with some extra precautions to keep infections away. My career in the pharmaceutical industry has given me insights that I am currently putting to use as an advocate to lower drug pricing, especially prices for anti-cancer drugs. I am a firm believer that staying mentally active, physically fit, compliant to our treatment regimen and taking an active interest in our disease are keys to successful treatment outcomes.