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Dendritic Versus Tumor Cell Presentation of Autologous Tumor Antigens for Active Specific Immunotherapy in Metastatic Melanoma: Impact on Long-Term Survival by Extent of Disease at the Time of Treatment.

Dillman RO, McClay EF, Barth NM, Amatruda TT, Schwartzberg LS, Mahdavi K, de Leon C, Ellis RE, DePriest C - Cancer Biother. Radiopharm. (2015)

Bottom Line: Treatment with DC-TC was associated with longer OS in both cohorts.Among 73 patients who had detectable metastases, OS was better for DC-TC: median 38.8 months versus 14.7 months, 5-year OS 33% versus 20% (p=0.025).This approach is promising as an adjunct to other therapies in patients who have had metastatic melanoma.

View Article: PubMed Central - PubMed

Affiliation: 1 Caladrius Biosciences, Inc. , Irvine, California.

ABSTRACT
In patients with metastatic melanoma, sequential single-arm and randomized phase II trials with a therapeutic vaccine consisting of autologous dendritic cells (DCs) loaded with antigens from self-renewing, proliferating, irradiated autologous tumor cells (DC-TC) showed superior survival compared with similar patients immunized with irradiated tumor cells (TC). We wished to determine whether this difference was evident in cohorts who at the time of treatment had (1) no evidence of disease (NED) or (2) had detectable disease. Eligibility criteria and treatment schedules were the same for all three trials. Pooled data confirmed that overall survival (OS) was longer in 72 patients treated with DC-TC compared with 71 patients treated with TC (median OS 60 versus 22 months; 5-year OS 51% versus 32%, p=0.004). Treatment with DC-TC was associated with longer OS in both cohorts. Among 70 patients who were NED at the time that treatment was started, OS was better for DC-TC: 5-year OS 73% versus 43% (p=0.015). Among 73 patients who had detectable metastases, OS was better for DC-TC: median 38.8 months versus 14.7 months, 5-year OS 33% versus 20% (p=0.025). This approach is promising as an adjunct to other therapies in patients who have had metastatic melanoma.

No MeSH data available.


Related in: MedlinePlus

Pooled data and algorithm to derive subsets of patients by active specific immunotherapy (ASI) treatment with dendritic cell-tumor cell (DC-TC) vaccine or TC vaccine, and stratified by no evidence of disease (NED) or detectable metastases (DM).
© Copyright Policy - open-access
Related In: Results  -  Collection


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f1: Pooled data and algorithm to derive subsets of patients by active specific immunotherapy (ASI) treatment with dendritic cell-tumor cell (DC-TC) vaccine or TC vaccine, and stratified by no evidence of disease (NED) or detectable metastases (DM).

Mentions: There were 74, 54, and 42 patients who had enrolled in the three successive trials for a total of 170 patients.4,5,9Figure 1 shows the derivation of the four different patient subsets that were the focus of this analysis. Based on previous analyses that showed inferior OS for patients who did not receive GM-CSF or IFN-γ as an adjuvant and/or did not receive a minimum of the first three injections,4 27 such patients were excluded from this analysis. In a randomized phase II trial of the Cancer Biotherapy Research Group (CBRG), 98 patients, including 51 with melanoma, were randomized to receive injections of TC along with injections of GM-CSF (n=49) or IFN-γ (n=49); there was no difference in survival or immune response.17 However, in trial (#1), there was a dramatic difference in survival, 26% versus 0% 5-year OS for 53 patients who received GM-CSF and/or IFN-γ as an adjuvant compared with 21 patients who did not (p<0.001).4 For this reason, in an effort to create a more closely matched group of patients, we excluded five TC patients who did not receive the first three weekly injections, and 20 TC patients who received neither GM-CSF nor IFN-γ as an adjuvant, which left us with 49 of the 74 patients. We also excluded 2 out of 24 TC patients from trial #3 who failed to receive the first three weekly injections. Thus, all 27 patients who were excluded came from the TC cohort: 7 were NED, and 20 had detectable disease. These excluded patients had a median survival of only 8.4 months, with 1-, 2-, and 3-year survival rates of only 44%, 26%, and 15%, respectively. Exclusion of the poor-prognosis 27 TC-treated patients left us with 49 TC patients from trial #1 and 22 TC patients from trial #3 for a total of 71 patients in the TC cohort for a comparison to the 72 DC-TC-treated patients.


Dendritic Versus Tumor Cell Presentation of Autologous Tumor Antigens for Active Specific Immunotherapy in Metastatic Melanoma: Impact on Long-Term Survival by Extent of Disease at the Time of Treatment.

Dillman RO, McClay EF, Barth NM, Amatruda TT, Schwartzberg LS, Mahdavi K, de Leon C, Ellis RE, DePriest C - Cancer Biother. Radiopharm. (2015)

Pooled data and algorithm to derive subsets of patients by active specific immunotherapy (ASI) treatment with dendritic cell-tumor cell (DC-TC) vaccine or TC vaccine, and stratified by no evidence of disease (NED) or detectable metastases (DM).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4492594&req=5

f1: Pooled data and algorithm to derive subsets of patients by active specific immunotherapy (ASI) treatment with dendritic cell-tumor cell (DC-TC) vaccine or TC vaccine, and stratified by no evidence of disease (NED) or detectable metastases (DM).
Mentions: There were 74, 54, and 42 patients who had enrolled in the three successive trials for a total of 170 patients.4,5,9Figure 1 shows the derivation of the four different patient subsets that were the focus of this analysis. Based on previous analyses that showed inferior OS for patients who did not receive GM-CSF or IFN-γ as an adjuvant and/or did not receive a minimum of the first three injections,4 27 such patients were excluded from this analysis. In a randomized phase II trial of the Cancer Biotherapy Research Group (CBRG), 98 patients, including 51 with melanoma, were randomized to receive injections of TC along with injections of GM-CSF (n=49) or IFN-γ (n=49); there was no difference in survival or immune response.17 However, in trial (#1), there was a dramatic difference in survival, 26% versus 0% 5-year OS for 53 patients who received GM-CSF and/or IFN-γ as an adjuvant compared with 21 patients who did not (p<0.001).4 For this reason, in an effort to create a more closely matched group of patients, we excluded five TC patients who did not receive the first three weekly injections, and 20 TC patients who received neither GM-CSF nor IFN-γ as an adjuvant, which left us with 49 of the 74 patients. We also excluded 2 out of 24 TC patients from trial #3 who failed to receive the first three weekly injections. Thus, all 27 patients who were excluded came from the TC cohort: 7 were NED, and 20 had detectable disease. These excluded patients had a median survival of only 8.4 months, with 1-, 2-, and 3-year survival rates of only 44%, 26%, and 15%, respectively. Exclusion of the poor-prognosis 27 TC-treated patients left us with 49 TC patients from trial #1 and 22 TC patients from trial #3 for a total of 71 patients in the TC cohort for a comparison to the 72 DC-TC-treated patients.

Bottom Line: Treatment with DC-TC was associated with longer OS in both cohorts.Among 73 patients who had detectable metastases, OS was better for DC-TC: median 38.8 months versus 14.7 months, 5-year OS 33% versus 20% (p=0.025).This approach is promising as an adjunct to other therapies in patients who have had metastatic melanoma.

View Article: PubMed Central - PubMed

Affiliation: 1 Caladrius Biosciences, Inc. , Irvine, California.

ABSTRACT
In patients with metastatic melanoma, sequential single-arm and randomized phase II trials with a therapeutic vaccine consisting of autologous dendritic cells (DCs) loaded with antigens from self-renewing, proliferating, irradiated autologous tumor cells (DC-TC) showed superior survival compared with similar patients immunized with irradiated tumor cells (TC). We wished to determine whether this difference was evident in cohorts who at the time of treatment had (1) no evidence of disease (NED) or (2) had detectable disease. Eligibility criteria and treatment schedules were the same for all three trials. Pooled data confirmed that overall survival (OS) was longer in 72 patients treated with DC-TC compared with 71 patients treated with TC (median OS 60 versus 22 months; 5-year OS 51% versus 32%, p=0.004). Treatment with DC-TC was associated with longer OS in both cohorts. Among 70 patients who were NED at the time that treatment was started, OS was better for DC-TC: 5-year OS 73% versus 43% (p=0.015). Among 73 patients who had detectable metastases, OS was better for DC-TC: median 38.8 months versus 14.7 months, 5-year OS 33% versus 20% (p=0.025). This approach is promising as an adjunct to other therapies in patients who have had metastatic melanoma.

No MeSH data available.


Related in: MedlinePlus