Triplet demonstrates activity in relapsed/refractory MM
SAN DIEGO—A three-drug combination produced “deep and durable” responses in patients with relapsed/refractory multiple myeloma (MM), according to a speaker at the 2018 ASH Annual Meeting.
Selinexor, dexamethasone, and daratumumab produced a response rate of 73% when given at the recommended dosing schedule to MM patients who had received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
Most responders had a very good partial response (VGPR), but there were no complete responses. At a median follow-up of 7.7 months, the median progression-free survival had not been reached.
The most common grade 3/4 adverse events (AEs) in this trial were hematologic toxicities.
Cristina J. Gasparetto, MD, of Duke University Medical Center in Durham, North Carolina, presented these results, from the phase 1/2 STOMP trial (NCT02343042), as abstract 599.*
Patients
As of November 15, the trial had enrolled 28 MM patients. At baseline, their median age was 68 (range, 44-77). There were 14 males and 14 females. The median time from diagnosis to study treatment was 5.9 years (range, <1 to 12.9 years).
Patients had received a median of 3 (range, 2 to 10) prior treatment regimens.
All 28 patients had received a proteasome inhibitor, and 61% of them (n=17) were refractory to the treatment. All 28 patients had also received an immunomodulatory drug, and 64% of them (n=18) were refractory to it.
Seventy-nine percent (n=22) of patients had undergone an autologous transplant, and 7% (n=2) had received prior daratumumab.
Treatment
Patients were treated in two concurrent cohorts.
One cohort included 25 patients who received selinexor at 100 mg once-weekly (QW), dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
The other cohort included three patients who received selinexor at 60 mg twice-weekly (BIW), dexamethasone at 20 mg BIW, and daratumumab at 16 mg/kg QW.
The recommended phase 2 dose and schedule was selinexor at 100 mg QW, dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
Safety
Among patients who received the recommended phase 2 dosing schedule, common treatment-related AEs included:
- Nausea (60%)
- Diarrhea (32%)
- Anorexia (28%)
- Vomiting (24%)
- Dysgeusia (20%)
- Fatigue (48%)
- Hyponatremia (28%)
- Insomnia (24%)
- Blurred vision (24%)
- Thrombocytopenia (64%)
- Anemia (48%)
- Leukopenia (44%)
- Neutropenia (44%)
- Lymphopenia (20%).
“[T]he weekly dose was better tolerated [with] only a couple of patients with grade 3 [gastrointestinal] toxicity,” Dr Gasparetto noted.
The most common grade 3/4 AEs were thrombocytopenia (44%), anemia (28%), leukopenia (28%), and neutropenia (24%). There were no grade 5 AEs.
Efficacy
The median follow-up was 7.7 months, and the median time on study was 5.8 months.
Twenty-six patients were evaluable for response, as two patients withdrew consent prior to follow-up.
The overall response rate was 73% (n=19), which includes seven very good partial responses (VGPRs) and 12 partial responses (PRs). Two patients had a minimal response, four had stable disease, and one progressed.
Among patients with a PR or better, the median time on treatment was 7.3 months. The median time to response was 1 month.
Three VGPRs are ongoing, but four patients who achieved a VGPR progressed.
Six PRs are ongoing, and one patient with a PR progressed. Other reasons for treatment discontinuation among patients with a PR included transplant (n=1), AE (n=1), patient decision (n=2), and hospice (n=1).
One patient with a minimal response progressed, and one discontinued treatment due to an AE.
The median progression-free survival was not reached.
