Daratumumab Plus Pomalidomide and Low-Dose Dexamethasone in Myeloma: Immune-Mediated Cytotoxicity
Posted: Thursday, December 17, 2020
According to results from the MM-014 study published in Clinical Cancer Research, the efficacy of the combination regimen of daratumumab, pomalidomide, and low-dose dexamethasone may be attributable to increased immune-mediated cytotoxicity. Certain immune subpopulations may experience superior survival outcomes with this triplet regimen.
“By employing novel cereblon-modulating agents along with additional emerging antibody-based therapies, such combinations may drive enhanced immune response along with cell autonomous direct tumoricidal activity,” concluded Samir Parekh, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues.
The primary analysis of the phase II study focused on arm B of a two-arm design. This arm included 112 patients with multiple myeloma who received the triplet regimen of daratumumab, pomalidomide, and low-dose dexamethasone for 28-day cycles until disease progression or unacceptable toxicity. Among the intent-to-treat population, 110 patients were designated as an immune biomarker subgroup. All patients had received prior lenalidomide treatment and had undergone a median of two previous antimyeloma treatment regimens.
During treatment, a decrease in natural killer cells and B cells was observed, in line with expectations for the daratumumab immune mechanism. However, the reduction in natural killer cells was mediated by the substantial increase in activated and proliferating natural killer and T cells, including CD38+ cells, associated with pomalidomide. This relationship seemed to be further enhanced by the daratumumab-caused elimination of CD38+ cells. These changes were noted even in patients who were determined to be lenalidomide-refractory. Patients with higher CD4+ levels at baseline and following treatments were more likely to achieve at least a very good partial response as well as 18-month progression-free survival.
Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournals.org.