Correlation between prior therapeutic dendritic cell vaccination and the outcome of patients with metastatic melanoma treated...

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Author(s): L. Pierret,
S. Wilgenhof, J. Corthals, T. Roelandt, K. Thielemans, B. Neyns; UZ
Brussel, Brussels, Belgium; Vrije Universiteit Brussel, Brussels,
Belgium
 
Abstract:
Background:
Ipilimumab (Ipi) is an anti-cytotoxic T lymphocyte associated antigen 4
(CTLA4) IgG1 monoclonal antibody active against metastatic melanoma.
Ipi acts by reinforcement of CTL-activation trough B7/CD28 receptor
stimulation. A pre- existing anti-tumor CTL repertoire, induced by
dendritic cell (DC) vaccination, could influence the therapeutic effect
of Ipi. The influence of prior DC-vaccination on the outcome of
melanoma patients (pts) treated with Ipi at a single center was
analyzed to evaluate this hypothesis.
 
Methods: Data were
obtained from the medical files of pts treated at the UZ Brussel with
Ipi in protocols CA184-022, -025, and the BMS Ipi medical need program.
Ipi (0.3, 3 or 10 mg/kg) was administered iv q3 wks x4 q12 wks
thereafter.
 
Results: 20 pts (10M/10F; med age 51y, range 28-72)
were identified. Prior therapy: autologous DC-vaccine loaded with
melanoma associated antigens (14 pts) ± IFN-a2b (9/14 pts), cytotoxic
agents (17 pts). Baseline characteristics: AJCC st IV melanoma (20
pts); baseline LDH > ULN (16 pts). Ipi dose: 0.3 mg/kg (4 pts), 3
mg/kg (2 pts), 10 mg/kg (14 pts). Serial LDH measurements were
available for 17 pts; 4 types of LDH-response following Ipi
administration were observed: increase (11 pts), decrease (1 pt),
fluctuation (4 pts), stable (1 pt). Objective response according to
mWHO or irWHO: 3 PR, 1 SD, 16 PD. One pt received 0.3 mg/kg of Ipi
(CA184-022) and had SD but no LDH response; at PD she received
DC-vaccine and subsequently 10 mg/kg Ipi (medical need program)
resulting in a fluctuating LDH-response and regression of an
orbita-metastasis. Increasing LDH values following Ipi were less often
observed in pts with prior DC-vaccination (5/6 pts (83%) without prior
DC-vaccination had increasing LDH-values vs 6/12 pts (50%) with prior
vaccination). DC- vaccination also correlated with regression of
metastases and disease control (3/15 pts (20%) who were vaccinated had
a PR/SD vs 1/6 (17%) PR for those who had not received prior
DC-vaccinations).
 
Conclusions: These data represent a small
sample size from a single institution; however, our results suggests a
potential correlation between prior therapeutic DC vaccination and
outcomes in advanced melanoma patients treated with ipilimumab.