Lulla et al. assessed the safety and efficacy of autologous, peripheral blood-derived multi-tumor-associated antigen (mTAA)-targeted T cells in patients with multiple myeloma (MM). Ex vivo-expanded mTAA T cells showed functional specificity towards stimulating antigens, but didn’t react against non-malignant cells. In 21 patients with MM, mTAA infusion was well tolerated at all doses administered. Out of 12 patients treated for active disease, one had SD at 19 months and another had PR at 45 months. Relapsed patients in the active disease group had downregulated target antigen expression or altered immune regulatory genes.
Contributed by Shishir Pant
ABSTRACT: Multiple myeloma (MM) is an almost always incurable malignancy of plasma cells. Despite the advent of new therapies, most patients eventually relapse or become treatment-refractory. Consequently, therapies with nonoverlapping mechanisms of action that are nontoxic and provide long-term benefit to patients with MM are greatly needed. To this end, we clinically tested an autologous multitumor-associated antigen (mTAA)-specific T cell product for the treatment of patients with high-risk, relapsed or refractory MM. In this study, we expanded polyclonal T cells from 23 patients with MM. T cells whose native T cell receptors were reactive toward five myeloma-expressed target TAAs (PRAME, SSX2, MAGEA4, Survivin, and NY-ESO-1) were enriched ex vivo. To date, we have administered escalating doses of these nonengineered mTAA-specific T cells (0.5 _ 10(7) to 2 _ 10(7) cells/m(2)) to 21 patients with MM, 9 of whom were at high risk of relapse after a median of 3 lines of prior therapy and 12 with active, relapsed or refractory disease after a median of 3.5 prior lines. The cells were well tolerated, with only two transient, grade III infusion-related adverse events. Furthermore, patients with active relapsed or refractory myeloma enjoyed a longer than expected progression-free survival and responders included three patients who achieved objective responses concomitant with detection of functional TAA-reactive T cell clonotypes derived from the infused mTAA product.