Post-ASH 2018: An Analysis of the CASTOR, POLLUX and MMY1001 Studies in Patients with Relapsed/Refractory Multiple Myeloma

Poster presentation by Dr. Saad Z. Usmani

This poster presentation is a subgroup analysis of two important phase III studies (POLLUX and CASTOR) and one phase I study (MMY1001). The purpose of this analysis is to validate the efficacy of adding daratumumab to standard therapy in patients with relapsed/refractory multiple myeloma (RRMM). The subgroup of patients studied had to either be refractory or have been exposed to lenalidomide.

POLLUX and CASTOR are two phase III studies that evaluated, respectively, the combination of daratumumab with lenalidomide/dexamethasone (D-Rd) and with bortezomib/dexamethasone (D-Vd). MMY1001 is a multi-arm phase Ib study evaluating patients with RRMM treated with daratumumab plus carfilzomib/dexamethasone (D-Kd) or daratumumab plus pomalidomide/dexamethasone (D-Pd).

A total of 493 patients who had been previously exposed to lenalidomide were included. The median progression-free survival (PFS) of patients in the CASTOR study was 9.5 months in the D-Vd arm (n = 89) versus 6.1 months in the Vd arm (n = 120); the difference was statistically significant. In the POLLUX study, the median PFS was also statistically higher, at 38.9 months in the D-Rd arm (n = 50) versus 18.6 months in the Rd arm (n = 50).

For patients who were refractory to lenalidomide (284 patients in the CASTOR and MMY1001 studies), the addition of daratumumab was also associated with a benefit in terms of PFS: in the CASTOR study, 7.8 months with D-Vd versus 4.9 months with Vd and in the MMY1001 study, 14.1 months with D-Kd versus 9.9 months with D-Pd.

In conclusion, the addition of daratumumab is associated with a clear benefit in terms of PFS in the population of patients already exposed or refractory to lenalidomide. This study reveals a very impressive PFS for the D-Rd combination (38.9 months) in a cohort of patients previously exposed to lenalidomide. If we consider the total population of the POLLUX study, the median PFS is 44.5 months (poster no. 1996), a result that has never been matched in a population of patients with RRMM.

In addition, this study is very useful in a Canadian context where a considerable number of patients will receive lenalidomide as first-line maintenance therapy following an autologous stem cell transplant, or lenalidomide/dexamethasone as first-line treatment for non-eligible patients.

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