Bortezomib, Lenalidomide, Dexamethasone plus transplant is a standard of care for eligible multiple myeloma patients.
As responses can deepen with time, regimens with longer and more potent induction/consolidation phases are needed.
In a phase II study, patients received eight 28-day cycles of Carfilzomib ( K; Kyprolis ) 20/36mg/m2 ( D1-2,8-9,15-16 ), Lenalidomide ( R; Revlimid ) 25 mg ( D1-21 ), and Dexamethasone ( d ) 20 mg ( D1-2,8-9,15-16,22-23 ).
All patients proceeded to transplant after 4 cycles and received 1-year Lenalidomide maintenance ( 10 mg, D1-21 ).
The primary objective was stringent complete response ( sCR ) at the completion of consolidation.
Overall, 48 patients were screened and 46 enrolled; 21% had adverse cytogenetics. Among 42 evaluable patients after consolidation, 26 were in sCR ( 61.9% ), 27 in CR or more ( 64.3% ): 92.6% had undetectable minimal residual disease ( MRD ) by flow cytometry ( greater than or equal to 2.5 x10-5 ) and 63.0% by next generation sequencing ( 10-6 ).
Median time to complete response was 10.6 months. By MFC and NGS, 69.0% and 66.7% patients, respectively had undetectable minimal residual disease at some point.
With a median follow-up of 60.5 months, 21 patients progressed and 10 died ( 7 from multiple myeloma ). Median progression-free survival was 56.4 months.
There was no KRd related death.
Four patients discontinued the program due to toxicities; 56 serious adverse effects were reported in 31 patients including 8 cardiovascular events ( 2 heart failures, 5 pulmonary embolisms or deep vein thrombosis ).
Common grade 3/4 adverse effects were hematological ( 74% ) and infectious ( 22% ).
In conclusion, 8 cycles of KRd produce fast and deep responses in transplant eligible newly diagnosed multiple myeloma ( NDMM ) patients.
Safety profile was acceptable but cardiovascular adverse effects should be closely monitored. ( Xagena )
Roussel M et al, Blood 2021; Online ahead of print