Carfilzomib Maintenance Improves Response in Relapsed Multiple Myeloma After Transplant
Orlando, FL—A conditioning regimen before autologous hematopoietic stem-cell transplant (HSCT) consisting of carfilzomib (Kyprolis) plus high-dose melphalan can help sustain posttransplant remission in patients with relapsed multiple myeloma who respond to transplant.
Of 48 patients who received carfilzomib plus melphalan as a conditioning regimen in a phase 1/2 clinical trial, the median time for engraftment was 10 days for neutrophils and 15 days for platelets, and no dose-limiting toxicities or nonhematologic grade 4 toxicities, said Luciano J. Costa, MD, PhD, Associate Professor of Medicine, Bone Marrow Transplantation and Cell Therapy Program, University of Alabama at Birmingham Hospital, at the 2017 BMT Tandem Meetings.
“Carfilzomib as single agent can be safely used as maintenance following carfilzomib/melphalan, and can sustain remission in most of the patients in this high-risk population,” he said.
Post-autologous HSCT maintenance therapy with thalidomide, lenalidomide (Revlimid), or bortezomib (Velcade) is well-established in the upfront setting, but data on the use of post-transplant maintenance therapy in the relapsed setting are limited, said Dr Costa.
The 2-phase investigation included a phase 1 dose-escalation study to determine the maximum tolerated dose of carfilzomib when added to melphalan conditioning for autologous HSCT in relapsed multiple myeloma, and a phase 2 study of the antimyeloma activity and toxicity of the preparative regimen. In addition, patients were surveyed to determine which of the 2 schedules of carfilzomib maintenance they preferred.
The 2 maintenance schedules were carfilzomib 36 mg/m2 on days 1, 8, and 15, or on days 1, 2, 15, and 16 for twelve 4-week cycles. Patients receiving maintenance had 2 cycles on each schedule, and then had their choice of schedules for the remainder of maintenance.
Patients were eligible for the study if they had relapsed multiple myeloma and had at least a minimal response to their latest line of therapy, which could include carfilzomib. Patients eligible for maintenance could not have had disease progression by 100 days posttransplant.
Overall, 48 patients who received a median of 3 previous lines of therapy were enrolled. Nearly all patients received previous bortezomib and lenalidomide, and approximately 66% had received previous autologous HSCT. Of the 48 patients, 2 were not eligible for the conditioning regimen and were included only in the toxicity analysis.
A total of 27 patients did not have disease progression by 100 days posttransplant and started maintenance therapy with single-agent carfilzomib. Of these 27 patients, 31% showed an improvement in a response category during maintenance.
The interim 12-month progression-free survival with maintenance was 67.5%. Furthermore, 9 patients are currently receiving therapy, and 10 patients have completed maintenance; 2 patients discontinued treatment because of toxicity, 1 because of grade 3 congestive heart failure, and 1 because of grade 4 acute kidney injury.
No dose-limiting toxicity was reported in the phase 1 or phase 2 cohort. Phase 2 proceeded with the expansion of the last dose of carfilzomib—27 mg/m2 on day 3 before melphalan therapy, followed by 56 mg/m2 on day 2 before melphalan. The main (38%) grade 3 or 4 nonhematologic toxicity during conditioning was infection. Two patients had disease progression from pretransplant to posttransplant.
Of the remaining 44 patients, 13.7% had a very good partial response or better preconditioning, which improved to 59.2% at 100 days posttransplant.
Patients were satisfied with either maintenance schedule. Of the 29 patients who were eligible for and consented to maintenance with carfilzomib, the proportion of patients with a very good partial response or better improved to 75.8%.