[11] In December 2011, the FDA granted Onyx standard review designation,[12][13] for its new drug application submission based on the 003-A1 study, an open-label, single-arm phase IIb trial.

The trial evaluated 266 heavily-pretreated patients with relapsed and refractory multiple myeloma who had received at least two prior therapies, including bortezomib and either thalidomide or lenalidomide.

[3] In a phase II trial (004), carfilzomib had a 53% overall response rate among patients with relapsed and/or refractory multiple myeloma who had not previously received bortezomib.

[18] In another phase II trial (006) of patients with relapsed and/or refractory multiple myeloma, carfilzomib in combination with lenalidomide and dexamethasone demonstrated an overall response rate of 69%.

[20][21] In phase II trials of carfilzomib, the most common grade 3 or higher treatment-emergent adverse events were hematologic toxicity [22] with thrombocytopenia, anemia, lymphopenia, neutropenia, pneumonia, fatigue and hyponatremia.

[24] Furthermore, gastrointestinal disturbances, including diarrhea and nausea are non hematologic group of side effects commonly reported with proteasome inhibitors.

Treatment discontinuation because of adverse effects occurred less frequently in the KRd arm, and events included thrombocytopenia, hypertension, and heart failure.