From the 1st January 2018, carfilzomib became available on the Pharmaceutical Benefits Scheme (PBS). Carfilzomib is indicated for the treatment of relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone, or dexamethasone alone. However, due to challenges demonstrating the cost-effectiveness of concomitant lenalidomide, the PBS criteria does not allow concurrent therapy with PBS-subsidised thalidomide or its analogues.

Carfilzomib is a second-generation proteasome inhibitor that selectively and irreversibly inhibits the activity of the constitutive proteasome and immunoproteasome. Malignant plasma cells are particularly reliant on proteasome function, possibly due to their high rate of protein synthesis and cell proliferation. Inhibition of these protein complexes leads to intracellular accumulation of ubiquitinated proteins with anti-proliferative and pro-apoptotic results.

The safety and efficacy of carfilzomib in combination with lenalidomide and dexamethasone was evaluated in the ASPIRE study using lenalidomide and dexamethasone as the control. A complete response or better was observed in 31.8% of the test group compared to 9.3% of the control. Mean progression-free survival was 26.3 months in the carfilzomib group compared to 17.6 months for the control, an increase of 8.7 months.

Adverse effects of any grade that occurred more frequently in the carfilzomib group included hypokalaemia, cough, upper respiratory tract infection, and thrombocytopenia. Adverse events of grade 3 or higher were reported in 83.7% of the test group compared to 80.7% of the control group. These more severe events included dyspnoea, cardiac failure, ischaemic heart disease, hypertension, and acute renal failure.

References:

  1. Kyprolis® (carfilzomib) Australian approved product information. North Ryde: Amgen Australia. Approved December 2016.
  2. Pharmaceutical Benefits Advisory Committee. Public Summary Document – July 2017 PBAC Meeting. Pharmaceutical Benefits Scheme; 2017.
  3. Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015; 372(2): 142-52.

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