Carfilzomib (Kyprolis), the next-generation proteasome inhibitor recently approved by the FDA for relapsed/refractory multiple myeloma, showed strong activity in the front-line setting when paired with lenalidomide (Revlimid) and low-dose dexamethasone (CRd).1
The study evaluated stringent complete responses in 53 newly diagnosed patients who received induction therapy with CRd and, in some cases, stem cell transplant. Patients continued CRd for cycles 9 to 24, and a few patients initiated maintenance therapy with lenalidomide at the last best tolerated dose.
Major Findings
At a median of 12 cycles, 98% of patients responded, including 81% with a very good partial response or better, 62% with a complete response, and 42% with a stringent complete response. There were no differences by disease stage or cytogenetics. Responses continued to improve with longer treatment, and M protein steadily decreased. Over 90% of the 22 patients who achieved at least a complete response had no evidence of minimal residual disease.
Responses after extended treatment included at least a near-complete response in 67% of patients and a stringent complete response in 45% after four or more cycles (median of 13), and at least a near-complete response in 78% and stringent complete response in 61% after eight or more cycles (median of 16). Progression-free survival was 97% at 12 months and 92% at 24 months. At a median follow-up of 13 months, only two patients progressed.
After extended treatment, patients continued to tolerate treatment well, with limited dose modifications. Peripheral neuropathy was observed in about 20% of patients after CRd induction, and persisted (grades 1 and 2) in only 11% during maintenance.
Looking Ahead
Michael E. Williams, MD, of the University of Virginia Cancer Center in Charlottesville, commented on the findings and their implications at the Best of ASCO Boston meeting. “The low risk of neuropathy with carfilzomib is encouraging, since this has been a problematic issue with bortezomib [Velcade].” He predicted that carfilzomib will find a place in the triple-drug regimens that have not been standard front-line therapy and which have led to deep remissions and disease control, especially when coupled with maintenance therapy.
“As we become able to control disease with regimens generating these durable remissions, I anticipate that over the next few years, fewer patients will be going to transplant early,” he said. ■
Disclosure: Dr. William has received research funding from and been a consultant for Celgene and Onyx.
Reference
1. Jakubowiak AJ, Dytfeld D, Griffith KA, et al: A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood 120:1801-1809, 2012.
