Comparing carfilzomib to bortezomid combined with cyclophosphamide and dexamethasone in patients with previously treated multiple myeloma

This trial was carried out to compare bortezomib (Velcade; V) and carfilzomib (Kyprolis; K) in combination with Cd (cyclophosphamide and dexamethasone) as second line treatment in patients with relapsed multiple myeloma (MM). The authors found the KCd is as effective as VCd and K can also be used as a maintenance treatment in these patients. 

MM is a form of cancer that comes from plasma cells (a type of white blood cell). Despite new treatments being developed MM remains incurable. MM can become resistant to therapies (refractory) and patients can often relapse (cancer occurring again) after treatment. 

Bortezomib (V) is an anti-cancer medication used in the treatment of MM. It blocks proteins found in MM cells called proteasomes. It is called a proteasome inhibitor (PI). This leads to cancer cell death. Carfilzomib (K) is also a proteasome inhibitor. Both V and K are successfully used for the treatment of MM. However, which agent provides better results for patients with previously treated MM in combination with Cd is still unknown.  

There were 300 patients with previously treated MM in this trial. 201 patients received KCd. 99 patients received VCd. Patients in the KCd group who responded to therapy then received either K maintenance or no maintenance. Maintenance therapy is meant to keep the cancer from returning. The average follow-up of patients was 13.9 months. 

After 24 weeks, more patients in the KCd group (40.2%) achieved a very good partial response (tumor shrinkage) compared to the KCd group (31.9%). KCd was also associated with a 48% higher overall response to therapy (84%) versus VCd (68.1%).

Patients treated with KCd were 48% more likely to not have any cancer cells left after therapy compared to VCd after 24 weeks. There was no significant difference in survival without cancer worsening and overall survival between groups. 

K maintenance therapy was associated with a longer survival without cancer worsening (11.9 months) compared to the no maintenance therapy group (5.6 months).

More patients in the VCd group stopped treatment (20%) compared to the KCd group (5.4%). Severe side effects were similarly common in both groups. However, side effects such as disease affecting peripheral nerves were more common in VCd-treated patients while heart-related side effects were more common in the KCd group.

The authors found that KCd is at least as effective as VCd in first relapse in patients with MM and K was also found to be an effective maintenance agent.

More patients in the VCd group stopped treatment early. This may have influenced the results.