Randomized, placebo-controlled, double-blinded chemo-immunotherapy clinical trial in a Pet Dog model of Diffuse Large B-cell Lymphoma
Mené sur 19 chiens ayant développé spontanément un lymphome diffus à grandes cellules B, cet essai randomisé évalue l'efficacité, du point de vue de la période avant progression et de la survie spécifique, et la toxicité d'une vaccination autologue en combinaison avec une chimiothérapie
Purpose: Active immunotherapy is a promising antitumoral strategy; however its use in combination with chemotherapy in dogs with large B-cell lymphoma (DLBCL) remains largely untested. Heat shock proteins (HSPs) bind the small peptides they chaperone (HSPPCs), allowing for immunization of the host against a large repertoire of tumor-associated antigens. Hydroxylapatite (HA) vehicles HSPPCs and acts as an immunologic adjuvant. Aim of this study was to show that an autologous vaccine with HA and tumor-derived HSPPCs is safe and therapeutically effective in dogs with DLBCL. Experimental Design: Nineteen dogs with naturally-occurring DLBCL were entered into a prospective randomized placebo-controlled double-blinded trial of HSPPCs-HA plus chemotherapy versus chemotherapy alone. Endpoints included time to progression (TTP), lymphoma-specific survival (LSS) and incidence of toxicoses. Results: Median first TTP after randomization to the vaccine arm was 304 days versus 41 days for the control arm (P = 0.0004). There was also a statistically significant difference in duration of second remission between the two groups (P = 0.02). Median LSS was 505 days for the vaccinated dogs versus 159 days for the unvaccinated dogs (P = 0.0018). Six vaccinated dogs achieved molecular remission, as shown by clonal IgH rearrangement. Toxicoses were comparable between the two treatment arms. Conclusions: The results of this trial demonstrate that the autologous vaccine tested here is safe and efficacious in prolonging TTP and LSS in dogs with DLBCL when used in combination with dose-intense chemotherapy. Based on these results, additional evaluation of this novel therapeutic strategy is warranted in human DLBCL.