Author(s): L. Pierret,
S. Wilgenhof, J. Corthals, T. Roelandt, K. Thielemans, B. Neyns; UZ
Brussel, Brussels, Belgium; Vrije Universiteit Brussel, Brussels,
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
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
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.
Correlation between prior therapeutic dendritic cell vaccination and the outcome of patients with metastatic melanoma treated...
Author(s): L. Pierret,