Hoag Institute for Research and Education

Newport Beach, CA, United States

Hoag Institute for Research and Education

Newport Beach, CA, United States
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Dillman R.O.,Hoag Institute for Research and Education | Dillman R.O.,Hoag Family Cancer Institute | Cornforth A.N.,California Stem Cell | Depriest C.,Hoag Institute for Research and Education | And 6 more authors.
Journal of Immunotherapy | Year: 2012

Only 10% of metastatic melanoma patients survive 5 years, even though many can achieve substantial tumor reduction by surgical resection and/or radiation therapy and/or systemic therapy. An effective, nontoxic, consolidation immunotherapy could benefit such patients. We initiated a randomized trial to compare 2 promising patient-specific immunotherapy cell products. Patients had to have a diagnosis of metastatic melanoma and availability of an autologous melanoma cell line. Patients were stratified by whether their most advanced stage had been regional or distant metastases, and by whether they had measurable disease at the time of treatment, then they were randomized to receive irradiated autologous proliferating tumor cells or autologous dendritic cells (DC) loaded with antigens from such cells. Both products were injected subcutaneously in 500 μg of granulocyte-macrophage colony stimulating factor, weekly for 3 weeks and then monthly for 5 months. Patients in the 2 arms did not differ in baseline characteristics. All patients received prescribed therapy. Treatment was well tolerated. At the time of initial analysis, with no patients lost to follow-up, 50% of patients deceased, and all surviving patients followed for at least 6 months after randomization, survival is superior in the DC arm (hazard ratio, 0.27; 95% confidence interval, 0.098-0.729) with median survival not reached versus 15.9 months, and 2-year survival rates of 72% versus 31% (P=0.007). This trial provides evidence that a DC vaccine is associated with longer survival compared with a tumor cell vaccine, and is consistent with previous data suggesting a survival benefit from this patient-specific immunotherapy. Copyright © 2012 by Lippincott Williams & Wilkins.


Dillman R.O.,Caladrius Biosciences Inc. | McClay E.F.,Institute for Melanoma Research and Education | Barth N.M.,Genomics Usa, Inc. | Amatruda T.T.,Minnesota Oncology | And 5 more authors.
Cancer Biotherapy and Radiopharmaceuticals | Year: 2015

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. © Copyright 2015, Mary Ann Liebert, Inc. 2015.


Dillman R.O.,Hoag Institute for Research and Education | Dillman R.O.,Hoag Family Cancer Institute | Dillman R.O.,Cancer Biotherapy Research Group | Depriest C.,Cancer Biotherapy Research Group | And 2 more authors.
Cancer Biotherapy and Radiopharmaceuticals | Year: 2014

Various published data show that in patients with metastatic melanoma, high-dose interleukin-2 (IL2) is associated with 5-year survival rates of 15% from treatment initiation. We previously reported a median survival of 15.6 months, and a 20% 5-year survival rate for 150 patients who were treated with inpatient IL2 (Cancer Biother Radiopharm 2012;27:337). In the current study, we sought to determine whether treatment with active specific immunotherapy (ASI) with patient-specific tumor stem cell vaccines derived from autologous tumor cell (TC) lines contributed to the survival result. Existing databases revealed that 32/149 IL2-treated patients also received ASI, while 117 did not. ASI was given within 12 months of IL2 therapy in 19/32 patients. Patients who received IL2 plus ASI had better overall survival (p<0.001) with longer median survival (39.5 vs. 12.0 months) and a higher 5-year survival rate (39% vs. 13%). Survival was better even after exclusion of 55 IL2-alone patients who died before 12 months of follow-up (p=0.12). In subset analyses, survival was longer for 25 patients who received ASI after IL2 than for 7 who received ASI before IL2 (5-year survival 46% vs. 14%, p<0.001) and for 16 patients who received a dendritic cell/TC-based ASI compared with 16 injected with irradiated TC (p=0.17). This retrospective study suggests that receipt of IL2 followed by a patient-specific melanoma stem cell vaccine is associated with better survival than IL2 alone. © Mary Ann Liebert, Inc.


Dillman R.O.,Hoag Institute for Research and Education | Dillman R.O.,Hoag Family Cancer Institute | McClure S.E.,Hoag Institute for Research and Education
Clinical Lung Cancer | Year: 2014

Background National data demonstrate minimal improvement in survival for patients diagnosed with lung cancer despite a number of apparent advances during the past 3 decades. We wished to know how demographic characteristics, staging, therapy, and survival have changed over time for patients with lung cancer who were accessioned to the cancer registry of a large community hospital in southern California.Patients and Methods Clinical features and survival data were collected on patients diagnosed during each of the successive 6-year eras of 1986 to 1991 (n = 812), 1992 to 1997 (n = 1072), 1998 to 2003 (n = 1209), and 2004 to 2009 (n = 1365).Conclusion Survival has steadily improved for patients in this community who were diagnosed with lung cancer. The explanations for this improvement are multifactorial, but include earlier stage at diagnosis, decreases in histologic types associated with active smoking, and increased use of systemic therapies.Results Median survival improved from 11 to 13 to 16 to 26 months and overall 5-year survival steadily improved from 16.5% to 19.1% to 24.0% to 31.1%. The proportion of patients with localized disease at diagnosis increased from 18.4% to 24.1% to 24.9% to 31.6%. Improvements in relative survival were much greater than have occurred nationally. Other obvious trends over time were increasing age of patients, increasing proportions with diagnoses of adenocarcinoma with concomitant decreases in squamous cell and small cell histologies, and decreases in the proportion of large cell carcinoma with reciprocal increases in neuroendocrine diagnoses. The use of chemotherapy for patients with local disease tripled in the most recent era. © 2014 Elsevier Inc.


Dillman R.O.,Hoag Institute for Research and Education | Barth N.M.,Hoag Institute for Research and Education | Vandermolen L.A.,Hoag Institute for Research and Education | Mahdavi K.,Hoag Institute for Research and Education | McClure S.E.,Hoag Institute for Research and Education
Cancer Biotherapy and Radiopharmaceuticals | Year: 2012

For more than 20 years interleukin-2 (IL2) was the preferred treatment for medically fit metastatic melanoma patients, but recently two new agents, ipilimumab and vemurafenib, were approved for stage IV disease. Single-institution data were used to determine the long-term survival rate for IL2-treated melanoma patients, and whether use of inpatient IL2 had declined recently. Between May 1987 and April 2010, 150 patients were hospitalized for high-dose, intravenous (i.v.) IL2. The average number of IL2 patients increased from 5.4 per year during 1987-1991 to 5.8 during 1992-1997 after regulatory approval of IL2, to 8.3 during 1998-2006 after a marketing indication in metastatic melanoma was granted, but dropped to 3.0 during 2007-2010. At the time of treatment, median age was 52 years; 27% were 60 years of age or older. At the time of analysis 122 patients were deceased. Median survival from the start date of IL2 treatment was 15.6 months, with a 20% 5-year survival. Among patients enrolled in clinical trials, there were as many nonresponders who survived 5 years as responders, which is consistent with a delayed immunotherapy benefit. In the absence of long-term survival data for these newer agents, IL2 probably should still be the preferred initial treatment for most patients with metastatic melanoma who are medically fit. © Copyright 2012, Mary Ann Liebert, Inc. 2012.


PubMed | Hoag Institute for Research and Education
Type: Journal Article | Journal: Clinical lung cancer | Year: 2014

National data demonstrate minimal improvement in survival for patients diagnosed with lung cancer despite a number of apparent advances during the past 3 decades. We wished to know how demographic characteristics, staging, therapy, and survival have changed over time for patients with lung cancer who were accessioned to the cancer registry of a large community hospital in southern California.Clinical features and survival data were collected on patients diagnosed during each of the successive 6-year eras of 1986 to 1991 (n = 812), 1992 to 1997 (n = 1072), 1998 to 2003 (n = 1209), and 2004 to 2009 (n = 1365).Median survival improved from 11 to 13 to 16 to 26 months and overall 5-year survival steadily improved from 16.5% to 19.1% to 24.0% to 31.1%. The proportion of patients with localized disease at diagnosis increased from 18.4% to 24.1% to 24.9% to 31.6%. Improvements in relative survival were much greater than have occurred nationally. Other obvious trends over time were increasing age of patients, increasing proportions with diagnoses of adenocarcinoma with concomitant decreases in squamous cell and small cell histologies, and decreases in the proportion of large cell carcinoma with reciprocal increases in neuroendocrine diagnoses. The use of chemotherapy for patients with local disease tripled in the most recent era.Survival has steadily improved for patients in this community who were diagnosed with lung cancer. The explanations for this improvement are multifactorial, but include earlier stage at diagnosis, decreases in histologic types associated with active smoking, and increased use of systemic therapies.


PubMed | Hoag Institute for Research and Education
Type: Clinical Trial, Phase III | Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) | Year: 2012

Only 10% of metastatic melanoma patients survive 5 years, even though many can achieve substantial tumor reduction by surgical resection and/or radiation therapy and/or systemic therapy. An effective, nontoxic, consolidation immunotherapy could benefit such patients. We initiated a randomized trial to compare 2 promising patient-specific immunotherapy cell products. Patients had to have a diagnosis of metastatic melanoma and availability of an autologous melanoma cell line. Patients were stratified by whether their most advanced stage had been regional or distant metastases, and by whether they had measurable disease at the time of treatment, then they were randomized to receive irradiated autologous proliferating tumor cells or autologous dendritic cells (DC) loaded with antigens from such cells. Both products were injected subcutaneously in 500 g of granulocyte-macrophage colony stimulating factor, weekly for 3 weeks and then monthly for 5 months. Patients in the 2 arms did not differ in baseline characteristics. All patients received prescribed therapy. Treatment was well tolerated. At the time of initial analysis, with no patients lost to follow-up, 50% of patients deceased, and all surviving patients followed for at least 6 months after randomization, survival is superior in the DC arm (hazard ratio, 0.27; 95% confidence interval, 0.098-0.729) with median survival not reached versus 15.9 months, and 2-year survival rates of 72% versus 31% (P=0.007). This trial provides evidence that a DC vaccine is associated with longer survival compared with a tumor cell vaccine, and is consistent with previous data suggesting a survival benefit from this patient-specific immunotherapy.

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