Combo with daratumumab could be alternative to ASCT in MM
Of the 3, 1 discontinued before day 1 of the second cycle due to toxicity, 1 had a dose reduction to 56 mg/m2 at day of the second cycle, and 1 escalated to 70 mg/m2 at day 8 of cycle 3.
Ultimately, all patients who remained on study were able to escalate to 70 mg/m2.
Safety
The hematologic treatment-emergent adverse events (TEAE) generally followed what has been observed in similar studies before, Dr Jakubowiak noted.
Hematologic TEAEs of all grades occurring in 30% or more of patients were lymphopenia (68%), thrombocytopenia (55%), anemia (46%), leukopenia (41%), and neutropenia (32%).
The most common non-hematologic TEAEs of all grades occurring in 30% of patients or more were diarrhea (73%), upper respiratory infection (59%) cough, constipation, and fatigue (50% each), dyspnea and insomnia (46%), nausea, rash, and back pain (41%), muscle spasm (36%), and vomiting, pain in extremity, hyperglycemia, and increased ALT (32%).
The most common grade 3/4 TEAEs were infrequent and many events had none of grade 3/4 severity.
The safety profile is consistent with what was previously reported for daratumumab or KRd, Dr Jakubowiak affirmed.
Serious TEAEs
Serious TEAEs occurred in 10 patients (46%), with many occurring in just 1 patient. Pulmonary embolism (PE) was the most frequent, occurring in 3 patients.
All patients were required to be on aspirin prophylaxis and 1 of the patients who had a PE discontinued therapy.
The number of patients with a serious TEAE reasonably related to an individual study drug were 3 (14%) for daratumumab, 5 (23%) for carfilzomib, 5 (23%) for lenalidomide, and 2 (9%) for dexamethasone.
The TEAEs of interest—tachycardia, congestive heart failure, and hypertension—occurred in a single patient each.
Overall, serious TEAEs were consistent with previous reports from KRd studies.
Echocardiogram assessment
Investigators conducted 30 systemic evaluations on the impact of this regimen on heart function. The investigators observed no change from baseline through the duration of treatment in patients’ left ventricular ejection fractions.
One patient developed congestive heart failure, possibly related to daratumumab or carfilzomib. This patient resumed treatment with a reduced carfilzomib dose, elected ASCT on study day 113, and ended treatment with a VGPR.
“In all,” Dr Jakubowiak said, “we feel that there is no apparent signal of adverse impact of the addition of daratumumab on cardiac function.”
Infusion times and reactions
Overall, IRRs occurred in 27% of the patients, “which appears lower than with previous daratumumab studies,” Dr Jakubowiak noted. And IRRs occurred more frequently during the first infusion than subsequent infusions.
The split-dose infusion time was very similar to that of second and subsequent cycles.
There were limited events related to infusions. All were grade 1 or 2 and most occurred in only a single patient.
Response rate
The median number of treatment cycles administered was 11.5 (range, 2.0 – 13.0). The best response was 100% PR or better, 91% achieved VGPR or better, 42% CR or better, and 29% a stringent CR.
The depth of response improved with duration of treatment. For example, the sCR rate increased from 5% after 4 cycles to 29% at the end of treatment.
PFS was an exploratory endpoint. One patient progressed at 10.8 months and the 12-month PFS rate was 94% with all patients alive.
Stem cell harvest and ASCT
“For many of us,” Dr Jakubowiak commented, “it’s also of interest how this regimen will impact stem cell harvest.”
Nineteen of 22 patients were deemed to be transplant eligible, and the median number of CD34+ cells collected from them was 10.4 x 106 cells/kg.
