Daratumumab is a human CD38 IgGκ monoclonal antibody that demonstrated significant activity and a manageable safety profile in combination with bortezomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma (RRMM).

Investigators of the CASTOR trial, led by Chanan-Khan, examined subgroups to compare the efficacy of daratumumab added to bortezomib/dexamethasone (DVd) in the bortezomib-naive and bortezomib-experienced patient populations. They also evaluated the efficacy of DVd versus Vd in patients who were refractory to lenalidomide as their last prior line of therapy. Median follow-up was 13.0 months. The following outcomes were observed by subset:

• Bortezomib-naive patients (n = 172): Median progression-free survival (PFS) was not reached with DVd, and was 7.5 months with Vd. The estimated 12-month PFS was 74.6% versus 32.3%, respectively.
• Bortezomib-exposed patients (n = 326): Median PFS was 12.4 months with DVd compared with 6.7 months with Vd. Estimated 12-month PFS rates were 51.3% and 15.2%, respectively.
• Lenalidomide-refractory patients (n = 105): Median PFS was 9.3 months with DVd versus 4.4 months with Vd.

Objective response rates, including rates of very good partial response or better, were significantly improved by DVd in all subsets.

These analyses confirm that the addition of daratumumab to Vd significantly improves outcomes for patients with RRMM, regardless of prior treatment with bortezomib. Importantly, the benefit of DVd versus Vd was maintained in patients who were refractory to lenalidomide as the last prior line of therapy.

Chanan-Khan AA, et al. 2016 ASH. Abstract 3313.