In a prior study, daratumumab (DARA) has demonstrated excellent clinical activity in combination with pomalidomide (POM) and dexamethasone (D) among relapsed or relapsed and refractory (R/RR) myeloma patients.1 While DARA is being evaluated in combination with other agents who are naïve to DARA or the backbone agent under evaluation, its utility is unclear among patients refractory to DARA or the combination agent.
This study evaluated 3 cohorts of patients receiving a combination of DARA-POM-D: cohort 1: patients naïve to both DARA and POM; cohort 2: patients refractory to DARA or POM; and cohort 3 (a subset of cohort 2): patients refractory to both DARA and POM. Researchers conducted a retrospective evaluation of 41 patients with relapsed or R/RR myeloma treated at a single site from January 2015 until July 2016.
Among the patients included in the analysis, the median age was comparable across cohorts at the time of DARA therapy initiation. All evaluable patients were lenalidomide-refractory, and 88% were bortezomib-refractory. Cohort 1 included 19 (46%) patients, cohort 2 included 22 (54%) patients, and cohort 3 included 12 (29%) patients. Median prior lines of therapy suggested that cohort 3 was a heavily pretreated group. High-risk cytogenetics for cohort 1:2:3 were 15.8% versus 31.8% versus 25%, respectively.
Common treatment-related adverse events (grade 3 or higher) included neutropenia (17 patients, 41%); anemia (12 patients, 29%); and thrombocytopenia (8 patients, 20%).
Patients in cohort 1 showed response rates of nearly 90%, and overall response rates of nearly 35% were seen in cohort 3. Progression-free survival was 7 months in all cohorts combined, and was 5 months in patients refractory to both DARA and POM (cohort 3). Notably, overall survival was 80% in cohort 3 after 8 months of follow-up.
These findings show that patients were able to recapture some of the response to agents to which they had become refractory, and lend support to further investigation of DARA-POM-DEX as a potential treatment option in heavily pretreated patients refractory to either or both DARA and POM.
Nooka AK, et al. ASH 2016. Abstract 492.
- Chari et al. ASH 2015.