ITOC2–017.
PROLONGED SURVIVAL FOR PATIENTS WITH RECURRENT GLIOBLASTOMA MULTIFORME WHO ARE TREATED WITH TUMOUR LYSATE-PULSED AUTOLOGOUS DENDRITIC CELLS
Bosch L. Marnixa, Prins M. Robertb, Liau Lindab. aNorthwest Biotherapeutics, Inc, Bethesda, MD, United States, b University of California, Neurosurgery, Los Angeles, United States
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 fol- lowing several cycles of adjuvant temozomolide chemotherapy, with autologous dendritic cells pulsed with autologous tumour cell lysate (DCVaxO`-L). Such treatment is intended to activate the immune sys- tem 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 deter- mined 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 pseudo- progression. Assessment of progression was done using modified RANO criteria.
Results: Nineteen (19) patients diagnosed with GBM were deter- mined to have rapid recurrence following radiation therapy with con- comitant temozolomide chemotherapy. The life expectancy for such patients is typically poor, and they were provided the DCVax-L treat- ment as part of a compassionate use approach in parallel to ongoing late stage clinical trials. Median overall survival in this cohort from ini- tial 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 demon- strates 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 2months 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, con- firmed after P1 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+chemo 8.3 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.
