Combo with daratumumab could be alternative to ASCT in MM
CHICAGO—Results of an open-label phase 1b study of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone (KRd) in newly diagnosed multiple myeloma (MM) patients have shown the combination to be highly effective, with an overall response rate of 100%.
Ninety-one percent of patients achieved a very good partial response (VGPR) or better, and 43% achieved a complete response (CR) or better.
Investigators had hypothesized that rather than using autologous stem cell transplant (ASCT) to improve results of treatment with KRd, the combination could alternatively be improved by incorporating daratumumab into a KRd regimen.
Andrzej Jakubowiak, MD, of the University of Chicago Medical Center in Illinois, presented the findings of the MMY1001 study at the 2017 ASCO Annual Meeting (abstract 8000*).
“I think what was one of the more important developments in myeloma last year,” Dr Jakubowiak said, “was data from randomized studies showing that adding daratumumab to either lenalidomide and dexamethasone in the POLLUX study or bortezomib and dexamethasone, a proteasome inhibitor, in the CASTOR study, improves responses, depth of response, and . . . dramatically improved progression-free survival.”
“[W]e have now the rationale to potentially combine daratumumab with both an IMiD and proteasome inhibitor,” he explained, “which led to the development of this phase 1b study in which we combined daratumumab with KRd and evaluated tolerability and efficacy.”
Study design
Twenty-two transplant-eligible or -ineligible newly diagnosed MM patients were enrolled on the study.
Treatment duration was planned to be 13 cycles or less and patients had the option to move to transplant after 4 cycles.
They could have no clinically significant cardiac disease and echocardiogram was required prior to transplant.
The dosing schedule was the established dosing schema for daratumumab and KRd with 2 notable differences in the 28-day cycles.
First, the daratumumab dose was a split dose. So patients received 8 mg/kg on days 1-2 of cycle 1, 16 mg/kg a week on cycle 2, 16 mg/kg every 2 weeks on cycles 3 – 6, and every 4th week thereafter.
The second difference was carfilzomib dosing was a weekly regimen with escalation from 20 mg/m2 on day 1, cycle 1 to 70 mg/m2 on day 8 of cycle 1.
Lenalidomide (25 mg on days 1-21 of each cycle) and dexamethasone (40 mg/week) were the standard regimens for these drugs.
The primary endpoint was safety and tolerability. The secondary endpoint was overall response rate (ORR), duration of response, time to response, and infusion-related reactions (IRR).
The study also had an exploratory endpoint of progression-free survival (PFS).
Baseline characteristics
Patients were a median age of 59.5 years (range 34 – 74). About two thirds were younger than 65 and one third were between 65 and 75.
A little over half were male and most (86%) were white.
A little more than half (55%) had an ECOG score of 0, 41% were ECOG 1, and 5% were ECOG 2.
Patient disposition
As of the cutoff date of March 24, 8 of the 22 patients enrolled (36%) discontinued treatment: 1 due to an adverse event (AE), 1 due to progressive disease, and 6 patients (27%) proceeded to ASCT.
Dr Jakubowiak pointed out that response was censored at this point for patients who proceeded to transplant.
The median follow-up was 10.8 months (range, 4.0 – 12.5) and the median number of treatment cycles was 11.5 (range, 1.0 – 13.0).
“What is of interest to many of us,” Dr Jakubowiak said, “is that patients were escalated to the planned dose of 70 mg/m2 by cycle 2 except for 3 patients.”
