Keith Stewart, MB, ChB:The 2 big studies that have been performed that have justified the use of daratumumab in a nontransplant-eligible patient are called ALCYONE trial, and they’re called MAIA study. The first trial was conducted predominantly in Europe, and it worked on the basis that bortezomib, melphalan, and prednisone was an accepted regimen in European circles for treatment of myeloma in older individuals, and to which the trial then looked at VMP[ bortezomib, melphalan, prednisone] versus VMP [bortezomib, melphalan, prednisone] and daratumumab in a randomized phase III fashion for patients who did not plan to go to autologous transplant.
There were quite dramatic differences in progression-free survival, overall response rate, and depth of response in favor of adding daratumumab to the VMP [bortezomib, melphalan, prednisone] cocktail. This has resulted in approval of that regimen, VMP DARAagain, bortezomib, melphalan, prednisone, and daratumumab—by the FDA and by the European agencies.
However, the use of melphalan in the United States fell out of fashion many years ago, and for that reason it is not a regimen that has been particularly embraced in the United States. Although it is, of course, quite feasible to give and does offer the opportunity to offer daratumumab to your patients.
The second large phase III trial, perhaps the 1 that is more impactful in the United States, is the MAIA study. The MAIA study built on the highly effective use of lenalidomide, or Revlimid, and dexamethasone, in older patients. The original studies of Rd [lenalidomide, dexamethasone] show superiority over melphalan-prednisone-thalidomide and melphalan-prednisone-lenalidomide with an overall progression-free survival of around 26 months for the Rd [lenalidomide, dexamethasone] combination.
The MAIA study took patients not destined to go to transplant. Over half of them were over 75 years of age, and used lenalidomide-dexamethasone at fairly standard dosing, 25 mg of lenalidomide daily for 21 out, 28 days. Dexamethasone at 40 mg once weekly. As a control arm, which did very well with about 30 months or 31 months of progression-free survival, versus the same 2 drugs, to which we added daratumumab. Daratumumab is given at 16 mg/kg once weekly for 8 weeks, once every 2 weeks for the next 16 weeks, and then once a month thereafter.
This was again a very positive study in favor of the use of daratumumab in this cocktail of DRd, daratumumab, Revlimid with dexamethasone. The overall response rate was about 93%. There was a dramatic improvement of progression-free survival, almost the halving of the risk of progression, at least until the time of the study was reported, and more than doubling or tripling of the depth of response in terms of minimal residual disease negativity. This was a positive study. It resulted in FDA approval of this regimen. It’s now perhaps a new standard of care in this patient population.
Transcript edited for clarity.
Case: 83-Year-Old Man With NDMM Ineligible for Transplant
History and Presentation:
Patient was started on D-Rd