Saad Z. Usmani, MD, FACP:What we observed in MAIA, just as in POLLUX, was that the daratumumab-lenalidomide-dexamethasone combination appears to be well tolerated. There is a higher incidence of neutropenia, as well as increased incidence of infections, particularly upper-respiratory infections, but it does not impede the survival outcomes. What is also important to note in the MAIA experience is that the lenalidomide dosing was modified more frequently on the experimental arm. Close to 76% of the planned dosing of lenalidomide was delivered in the experimental arm, compared with the standard-of-care arm. This observation was also seen in POLLUX and observed with pomalidomide. From a clinical standpoint and from my experience, when we’re combining daratumumab with the immunomodulatory drugs, we will likely be dose reducing patients fairly quickly in this first cycle or 2.
The GRIFFIN trial is a phase I/randomized phase II trial that began in the United States roughly 2 years ago. It had a safety phase I run-in, which included 16 patients. Essentially, the idea was to see the safety implications of combining daratumumab with RVD [lenalidomide-bortezomib-dexamethasone] as part of induction and consolidation in transplant-eligible patients. The results presented at ASH [American Society of Hematology Annual Meeting & Exposition] in December 2018 showed there were no major safety implications in terms of increase in infections or ability to collect stem cells in patients or posttransplant recovery of neutrophil counts and platelet counts. These are very important pieces of information that were necessary to be generated in the safety run-in part of the trial before the randomized portion could be begin.
The randomized portion of the trial consists of 200 patients. The trial is fully enrolled. It randomized patients to the standard of careRVD induction, stem cell transplant, followed by consolidation and then maintenance with lenalidomide. The experimental arm added daratumumab to each of these stages of treatment in terms of induction and consolidation, followed by maintenance. We are waiting for the data to mature and inform us on the implications of incorporating daratumumab into the frontline setting for transplant-eligible patients. We know right now that it is a safe strategy. We’re simply looking for the efficacy signal.
In terms of the efficacy results of the phase I run-in portion of the GRIFFIN trial, the VGPR [very good partial remission]or-better rates were 63%. These included complete responses and stringent complete responses. MRD [minimal residual disease] negativity was achieved in 8 of 16 patients. It is important to note that the median follow-up was about 15.6 months, and we know that responses do deepen over time. In the update, we hope for these responses to continue to deepen with higher rates of MRD negativity.
All the subjects in the phase I run-in portion of the GRIFFIN trial were able to proceed with stem cell transplantation. Fifteen of 16 patients remained progression-free at the time the study was being reported.
From a safety-analysis standpoint in the phase I portion on those 16 patients in GRIFFIN, the most important thing to note is the cytopenias that were observed. They’re consistent with what we see with RVD [lenalidomide-bortezomib-dexamethasone]. They were seen in 10 of 16 patients. The infusion-related reactions are probably important to note. They were seen in 31% of the patients, and a majority of those were patients who were receiving daratumumab for the first time. These rates are certainly lower than what have been reported for other frontline or even early relapsed trials and probably represent the use of montelukast sodium as a premedication for these patients.
The most common grade 3 or higher adverse events on the safety run-in portion of GRIFFIN included hematologic adverse events, febrile neutropenia, as well as pneumonia episodes. None of these adverse events led to the discontinuation of subjects from the study.
Transcript edited for clarity.