The introduction of monoclonal antibodies and immunomodulators into earlier lines of therapy may improve progression-free survival (PFS) in patients with refractory multiple myeloma (MM), according to a study reanalyzing clinical data collected at the Winship Cancer Center at Emory University in Atlanta, Georgia. Results were published in Cancer.

In the original study, 34 patients with refractory or relapsed MM received daratumumab administered intravenously, as well as pomalidomide and dexamethasone administered orally, for a median of 10.5 cycles.

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The patients were grouped into 3 cohorts. Cohort 1 included 12 patients who were daratumumab- and pomalidomide-naive. Cohort 2 included 22 patients who were refractory to daratumumab or pomalidomide. Cohort 3 was a subgroup of cohort 2 and included 12 patients who were refractory to both daratumumab and pomalidomide. Patients in all cohorts were refractory to lenalidomide and 91% of patients overall were refractory to bortezomib.

Overall response rate (ORR) was highest in cohort 1, at 91.7%. In cohort 2 the ORR was 40.9% and in cohort 3 the ORR was 33.3%. Four patients in cohort 1 experienced a complete response, while 8 patients in cohort 2 experienced partial responses.

Median PFS was 3.2 months in cohort 2 and 3.3 months in cohort 3. In cohort 1, median PFS was not reached after a median follow-up of 41 months. The authors noted that PFS in cohort 1 was more than quadruple the PFS previously reported in the phase 1b EQUULEUS trial (ClinicalTrials.gov Identifier: NCT01998971).

The tolerability of this combination therapy was consistent with the safety symptoms reported in the EQUULEUS study. There was a 41% rate of neutropenia in all patients, and anemia and thrombocytopenia were observed at rates of 32% and 24%, respectively.

The authors concluded that prospective clinical trials are warranted to assess the efficacy and safety of daratumumab re-treatment in relapsed or refractory MM.

Reference

1.     Nooka AK, Joseph NS, Kaufman JL, et al. Clinical efficacy of daratumumab, pomalidomide, and dexamethasone in patients with relapsed or refractory myeloma: Utility of re‐treatment with daratumumab among refractory patients [published online May 15, 2019]. Cancer. doi:10.1002/cncr.32178