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Background
Recurrent glioblastoma multiforme (rGBM) is a life threatening condition, with a mortality
rate of approximately 100%. Despite recent advances in therapy, the survival rate
in rGBM patients has not meaningfully changed in the past several decades. We have
treated two cohorts of rGBM patients, one consisting of patients with early progression,
and one consisting of patients with progression following several cycles of adjuvant
temozomolide chemotherapy, with autologous dendritic cells pulsed with autologous
tumour cell lysate (DCVax®-L). Such treatment is intended to activate the immune system
against the tumour cells, with the expectation that the ensuing immune attack may
delay progression and time to death.
Aim
To determine survival characteristics of patients with rGBM who are treated with DCVax-L.
Methods
Disease progression in patients with GBM was determined through magnetic resonance
imaging. Progression needed to be determined by independent review on two consecutive
scans for early progressor classification to avoid enrolling patients with pseudoprogression.
Assessment of progression was done using modified RANO criteria.
Results
Nineteen (19) patients diagnosed with GBM were determined to have rapid recurrence
following radiation therapy with concomitant temozolomide chemotherapy. The life expectancy
for such patients is typically poor, and they were provided the DCVax-L treatment
as part of a compassionate use approach in parallel to ongoing late stage clinical
trials. Median overall survival in this cohort from initial GBM diagnosis is 15.1 months (95% confidence interval (CI): 10.5–17.2), and the range is 8.1–>31 months. A literature search revealed six publications with comparable populations
of patients (Brandes et al., 2008; Roldan et al., 2009; Sanghera et al., 2010; Kang
et al., 2010; Gunjur et al., 2011; Linhares et al., 2013). The table below demonstrates
that these patients typically have a life expectancy of 8–10 months.
Reference (n) Population Median Survival (95% CI)
DCVax-L (19) post RT+chemo, confirmed 2 months later 15.1 months (10.5–17.2)
Brandes et al. (2008) (18) PD at 4 weeks pos RT+chemo, confirmed after two more tmz cycles 10.2 months (n.a.)
Roldan et al. (2009) (10) PD at 4–6 weeks post RT+chemo, confirmed after 1 more tmz cycle(s) 9.1 months (4.9–19.1)
Kang et al. (2010) (10) PD at two consecutive scans post RT+chemo 10.8 (n.a.)
Sanghera et al. (2010) (29) PD at two consecutive scans within 8 weeks post RT+chemo8.3 months (n.a.)
Gunjur et al. (2011 (27) PD at two consecutive scans within 3 months post RT+chemo, or clinical deterioration 10.4 months (n.a.)
Linhares et al. (2013) (13) PD at two consecutive scans within 3 months post RT+chemo 9.0 months (3.7–14.3)
A second cohort of patients with rGBM consisted of eight patients with recurrence
following several adjuvant temozolomide treatment cycles. Median overall survival
(OS) for these patients is 14.7 months from the time of surgery for first recurrence. The comparator for this cohort
is derived from Friedman et al. (2009), who reported mOS of 8.7–9.3 months from the time of first recurrence for rGBM patients treated with Bevacizumab
with or without irinotecan.
Results and conclusion
The results obtained in two cohorts of patients with rGBM suggest that treatment with
autologous DC pulsed with autologous tumour cell lysate can extend survival by 5 months or more.
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