Therapeutic Advancements in Multiple Myeloma - Episode 2

Newly Diagnosed Multiple Myeloma

There have been many advances in the treatment of multiple myeloma. And although these advances usually get approved and utilized in far advanced relapsed/refractory myeloma, they rapidly move to initial use, not as single agents but in combinations. So in patients with newly diagnosed myeloma, we consider 2 groups: the transplant eligible patients and the transplant ineligible patients. And we also consider 2 risk groups: those with standard-risk myeloma and those with high-risk myeloma. And I'll mention for example, the hyper diploid multiple myeloma would be standard risk, and high risk would be those patients who have 17 p deletion or amplification of chromosome one q, for example.

What's happened is we've moved to triplet therapies. It is commonly utilized now. That is a triplet regimen is commonly utilized of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone, also called RVD. It's so effective in terms of the extent and frequency of response, clinical trials have attempted to determine whether RVD is so effective that a transplant no longer adds value. As of the present time, transplant does add value, so RVD followed by high dose melphalan and transplant, and lenalidomide maintenance is a standard of care for the newly diagnosed transplant eligible. In the transplant ineligible patients, the same regimen RVD but at reduced doses, also called RVD light, is frequently utilized.

Now what's new this year is the incorporation of CD38 antibody targeting daratumumab (Darzalex) into the upfront regimen in both the transplant ineligible and the transplant eligible patients. So in North America, we have the GRIFFIN trial that compared RVD before transplant RVD after transplant, and lenalidomide maintenance, with the other arm being RVD plus daratumumab before transplant. RVD plus daratumumab is consolidation and then Revlimid plus daratumumab is maintenance. This trial was updated at the American Society of Hematology and although the response rates are high, whether you receive RVD or RVD-daratumumab in the transplant paradigm, the minimal residual disease negative rate was much higher and persistently higher. In other words, it was higher after induction. It was higher after consolidation and it was high during maintenance when daratumumab was incorporated.

So it is becoming a standard of care now that the CD38 antibody is moving up front in the transplant eligible newly diagnosed patients. A similar story in the transplant ineligible patients the Maya trial utilized lenalidomide decks with or without daratumumab and demonstrated an increased extent and frequency of response, prolonged duration of response and increased MRD negativity rates when daratumumab was added. And there's just a recent review in JAMA Oncology, which shows that this benefit of adding CD38 animosities to the initial management of myeloma is not only benefiting the standard risk patients, but also those with high risk disease as well.