Cristina Gasparetto, MD
The combination of daratumumab (Darzalex), selinexor, and dexamethasone continued to demonstrate deep and durable responses in patients with multiple myeloma who have previously received ≥3 lines of therapy, which include an immunomodulatory (IMiD) agent and a proteasome inhibitor, according to updated phase Ib findings presented at the 2018 ASH Annual Meeting.
, Cristina Gasparetto, MD, professor of medicine and director of the myeloma program at Duke Cancer Institute, discussed the findings from this trial and how the results compare to data from the STORM trial.
OncLive: Can you give an overview of this trial?
: This was a combination of selinexor, daratumumab, and dexamethasone. This combination is actually one of the arms of the STORM study. Selinexor is an oral selective inhibitor of exportin 1 (XPO1), which is the major nuclear export for many tumor suppressing proteins, oncoproteins, and glucocorticoid receptors. Selinexor has been tested in combination with low-dose dexamethasone and yields an overall response of about 26% in heavily pretreated patients.
The STORM study was designed to target relapsed/refractory multiple myeloma. Selinexor was combined with different backbone therapies for myeloma, bortezomib plus dexamethasone, carfilzomib plus dexamethasone, lenalidomide, pomalidomide, etc. I presented the results for selinexor [plus] daratumumab.
What are the safety and efficacy findings so far?
We enrolled 28 patients so far, and the primary objective of this study was to determine the recommended dose for a phase II portion of this study, to find the maximum tolerated dose. [Of the] enrolled 28 patients, 3 patients were enrolled in the first cohort where selinexor was given biweekly, but it was not really well tolerated in combination with daratumumab, so the next cohort was [given] 100 mg once a week. That was clearly relatively well tolerated. We didn’t have any dose limiting toxicities, so selinexor 100 mg with daratumumab as prescribed and dexamethasone once a week is the recommended phase II dose for the phase II portion.
The toxicity was similar to the STORM study, where selinexor was given in combination with dexamethasone, but in the STORM study, selinexor was given twice a week. In this study, it was once a week. We have seen the same type of toxicity, but the majority of patients have grade 1 and grade 2 gastrointestinal toxicity with only few patients having grade 3 nausea and vomiting. The majority were manageable. We also had some constitutional symptoms: fatigue, weight loss, and hyponatremia, with a few patients having grade 3 hyponatremia. Overall, I think the once a week administration was more tolerable, and with proper care and dose adjustment, these patients are able to tolerate the drug for a long period of time. We also have seen an immunologic toxicity, such as in the STORM study, with thrombocytopenia most predominant, but also some anemia and neutropenia.
In terms of efficacy, we had 26 patients evaluable for response, and 24 were daratumumab-naïve. They’ve never received daratumumab. As part of the inclusion criteria, the study patients had to have failed at least 3 prior lines of therapy, including proteasome inhibitors and IMiDS, or were refractory to PIs and IMiDS. The median prior regimens was about 3. All patients were exposed to IMiDs and PIs and the overall response was 79% for patients who were daratumumab-naïve. We then dissected the population, and the responses remained the same, still very high in the 80% range, even in patients who were exposed to both lenalidomide, pomalidomide, carfilzomib, bortezomib, so their response really didn’t change based on their prior lines of therapy.
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