Role of Novel Subcutaneous Daratumumab in Multiple Myeloma - Episode 1
Ola C. Landgren, MD, PhD: The role of daratumumab in the setting of multiple myeloma continues to move forward almost every month. It was initially FDA approved in November 2015 for the indication of relapsed/refractory myeloma. Initial approval was as a single drug. In less than 12 months, the first trials read out for combination therapy with lenalidomide [Revlimid]–dexamethasone and bortezomib-dexamethasone. After that, pomalidomide-dexamethasone was added. It kept on coming, and now we have an approval for the newly diagnosed patients. In mid-2019, daratumumab was approved by the FDA for patients with a new diagnosis of myeloma who are nontransplant candidates, in combination with lenalidomide and dexamethasone, as the up-front treatment. This comes from the MAIA study.
There have been additional approvals after that. The combination of thalidomide, bortezomib, dexamethasone, and daratumumab was approved in 2019. This is not the combination we typically use in the United States. It’s more of an ex-US treatment combination. Just a few weeks ago, the GRIFFIN study was published in Blood. This is a combination of bortezomib, lenalidomide, dexamethasone, and daratumumab showing superiority over the traditional VRd [bortezomib, lenalidomide, dexamethasone] regimen.
There are ongoing phase 3 trials for newly diagnosed patients with and without transplantation. There are ongoing studies using the KRd [carfilzomib, lenalidomide, dexamethasone] regimen with or without daratumumab. I think daratumumab has already established itself as a great treatment as a single drug and in combination in the relapsed/refractory setting, now moving up to earlier lines. It has already moved up to the newly diagnosed setting, and it’s expanding with more established US combinations up front. As a consequence of these studies, there is also ongoing work to look at it as an extended dosing option in the maintenance setting with or without Revlimid, so that will be very exciting to see. It’s literally everywhere.
We use daratumumab very frequently in our clinical program, and we use it for the indications provided by the FDA and supported by the NCCN [National Comprehensive Cancer Network] Guidelines, both in the newly diagnosed setting with lenalidomide-dexamethasone—the MAIA indication—as well as in the relapsed/refractory setting. We use it commonly for patients who relapse on lenalidomide maintenance therapy. We commonly would partner it with pomalidomide-dexamethasone. Some of us combine it with the bortezomib and dexamethasone. We have ongoing trials using KRd with daratumumab versus KRd without daratumumab; there is a control arm with VRd as part of that study, so it’s a 3-arm study. This is in the newly diagnosed setting, and we’re just about to open a maintenance study where we will investigate daratumumab as a single drug with subcutaneous administration. It’s a randomized study comparing it with lenalidomide on the other arm.
Transcript edited for clarity.