Day 90 CR not a good endpoint for auto-HSCT, doc says
Photo by Rhoda Baer
SAN DIGEO—A phase 3 study comparing conditioning regimens in multiple myeloma patients undergoing autologous transplant has yielded counterintuitive results.
Patients who received busulfan plus melphalan (bu-mel) had a lower complete response (CR) rate at 90 days and a higher rate of grade 3-4 non-hematologic
toxicity, compared to patients who received melphalan (mel) alone.
However, patients in the bu-mel arm enjoyed significantly longer progression-free survival (PFS).
These results suggest the rate of CR at 90 days is not a good endpoint for trials of autologous hematopoietic stem cell transplant (auto-HSCT), said Muzaffar H.
Qazilbash, MD, of The University of Texas MD Anderson Cancer Center in Houston.
Dr Qazilbash presented these and other findings at the 2015 BMT Tandem Meetings as abstract 83.*
“High-dose melphalan at 200 mg/m2 is considered the standard of care for autologous stem cell transplantation for multiple myeloma,” he said. “However, most patients have disease recurrence or progression after an autologous transplant, even with the use of post-transplant maintenance.”
A recent retrospective study suggested that bu-mel might be associated with a longer PFS compared to mel alone. So Dr Qazilbash and his colleagues decided to
investigate that possibility in a randomized, phase 3 trial.
The trial included 92 patients with symptomatic multiple myeloma who had received at least 2 cycles of induction therapy. They were all within 12 months of the start of induction, and all had adequate cardiac, pulmonary, renal, and liver function.
Forty-nine patients received bu-mel—a 130 mg/m2 daily infusion of busulfan for 4 days, followed by 2 daily doses of melphalan at 70 mg/m2. All patients in this arm also received phenytoin for seizure prophylaxis. The 43 patients in the mel-only arm received a single dose of melphalan at 200 mg/m2.
Baseline characteristics were similar between the 2 arms. The patients’ median ages were 58 in the bu-mel arm and 59 in the mel arm. At the time of transplant, 18% of patients in the bu-mel arm were in CR or near CR, as were 28% of patients in the mel arm.
Adverse events
At 100 days post-transplant, the transplant-related mortality was 0% in both arms.
“There was a significantly higher rate of grade 3-4 non-hematologic adverse events in the busulfan-plus-melphalan arm—78% vs 47% [P=0.002],” Dr Qazilbash noted. “And these adverse events were mostly infectious events.”
Grade 3 infection occurred in 71% of bu-mel-treated patients and 39% of mel-treated patients (P=0.003). Grade 2 gastrointestinal toxicities occurred in 69% and 48%, respectively (P=0.05).
There were no significant differences between the arms with regard to other adverse events. And there were no second primary malignancies in either arm.
Response
At 90 days, the CR rate was 16% in the bu-mel arm and 35% in the mel arm (P=0.05). The rates of CR plus very good partial response were 63% and 81%, respectively (P=0.06).
“The trial was stopped early, based on a prescribed rule in the trial design, because of a significantly higher CR rate in the control arm,” Dr Qazilbash said.
Still, he noted that, at 180 days, the CR rate was 26% in the bu-mel arm and 37% in the mel arm (P=0.36). And the 180-day rates of CR plus very good
partial response were 69% and 86%, respectively (P=0.65).
Maintenance
A majority of patients received maintenance therapy post-transplant—84% of patients in the bu-mel arm and 88% in the mel arm.
The median interval between auto-HSCT and maintenance was 4.6 months and 4.5 months, respectively. And the median duration of maintenance was 16 months and 14.2 months, respectively.
