K562/GM-CSF vaccination reduces tumor burden, including achieving molecular remissions, in chronic myeloid leukemia (CML) patients (PTS) with residual disease on imatinib mesylate (IM)

Abstract

6509 Background: Despite high rates of clinical responses to IM, molecular complete responses are rare. The curative potential of allo transplantation and donor lymphocyte infusions underscores CML’s responsiveness to T cell mediated immunity. K562/GM-CSF is a tumor vaccine derived from a CML cell line that expresses several defined CML associated antigens and has been genetically engineered to produce GM-CSF. A pilot vaccination strategy was developed to determine if K562/GM-CSF immunotherapy in combination with IM could enhance T cell reactivity and clinical responses in pts having persistent, measurable disease despite 1 or more years on IM. Methods: Eligibility required pts to have achieved a major cytogenetic response (<35% Ph+ cells) while on a stable dose of IM. Disease burden was measured serially over 12 wks prior to vaccines. 4 vaccines were administered in 3 wk intervals, each consisting of 1 × 10 8 irradiated K562/GM-CSF cells distributed over 10 sites, with or without topical 5% Aldara (a Toll-like receptor 7 agonist) used as a vaccine adjuvant. Disease burden was measured at 6 wk intervals for 9 mos from the first vaccine and specimens were banked for measurement of immune responses. Results: The trial enrolled 19 pts, all have completed the planned 4 vaccinations and 14 pts have completed all planned disease burden measurements. The median age is 52 (range 28–76) yrs with a median time from dx to enrollment of 57 (range 16–111) mos. Pts were on IM for a median of 37 (13–53) mos prior. 4 of 19 pts had FISH pos as their best previous response (BPR) with 2 becoming FISH neg post-vaccine (1 became PCR neg and 1 achieved a >1 log reduction in disease burden by PCR). Of the 15 pts whose BPR was FISH neg/PCR pos, 4 are now PCR neg post vaccine, 4 experienced a >1 log and 1 had 0.5–0.99 log reduction by PCR. Mean PCR levels for the 19 pts declined btwn pre- and post-vaccine measures (p=0.01). 3 of 5 pts achieving PCR neg remain so beyond 6 months. Only 1 pt progressed having entered the study with a heavy disease burden (30% FISH pos). Conclusions: K562/GM-CSF vaccine appears to improve responses in pts on IM, including achieving complete molecular remissions, despite long durations of previous IM therapy. [Table: see text]