Short-term autologous tumor cell lines for the active specific immunotherapy of patients with metastatic melanoma

Robert O. Dillman, Cristina DeLeon, Linda D. Beutel, Neil M. Barth, Lee Schwartzberg, Lynn E. Spitler, David H. Garfield, Audrey A. O'Connor, Shankar K. Nayak

Research output: Contribution to journalArticle

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Abstract

We established short-term cell lines for 108/170 (64%) patients with metastatic melanoma. Tumor cell numbers were expanded to 108, then cells were irradiated, aliquoted, and cryopreserved for clinical use. Vaccines have been used to treat 69 patients with clinical follow up for 33 who had measurable metastatic disease at the time vaccine therapy was initiated (METS), and 33 who had no evidence of disease (NED) at the time of vaccine therapy following surgical resection of metastases. The protocol called for a baseline test of delayed tumor hypersensitivity (DTH), three weekly injections, a repeat of the DTH test, then monthly injections for an additional 5 months. Objective tumor responses were noted in 3/26 (12%) patients who received a minimum of three vaccinations, one complete, and two partial, with survivals of 36, 46+, and 78+ months. Only 6/64 (9.4%) had a positive DTH (>10 mm) at baseline, including three METS, all of whom progressed within 4 months and died within a year, and three who are still NED after more than 5 years. Conversion of DTH from negative to positive was documented in 18/44 (41%) patients who were tested at week 0 and 4. At a median follow up of greater than 5 years, the median overall survival (OS) was 40 months for 'NED' with a 5-year survival rate of 39%, and 8.6 months with a 5-year survival rate of 10% for 'METS'. The 18 patients who had conversion of their DTH had a median event-free survival (EFS) of 15.8 months and 5-year EFS of 32% compared to 4.2 months and 9% for the 26 non-converters (P=0.012, two-tailed, log-rank test). Among patients who were NED when treatment started, the 12 patients whose DTH converted had a median overall survival of 61.4 months with 5-year survival of 63% compared to 9.7 months and 0% for the 13 non-converters (P=0.0026). This treatment approach is feasible, produces minimal toxicity, and is associated with long-term survival in a significant subset of patients.

Original languageEnglish (US)
Pages (from-to)115-123
Number of pages9
JournalCritical Reviews in Oncology/Hematology
Volume39
Issue number1-2
DOIs
StatePublished - Jul 4 2001

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Active Immunotherapy
Tumor Cell Line
Melanoma
Delayed Hypersensitivity
Neoplasms
Survival
Disease-Free Survival
Survival Rate
Injections
Vaccination
Vaccines
Cell Count
Neoplasm Metastasis
Cell Line
Therapeutics

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Geriatrics and Gerontology

Cite this

Short-term autologous tumor cell lines for the active specific immunotherapy of patients with metastatic melanoma. / Dillman, Robert O.; DeLeon, Cristina; Beutel, Linda D.; Barth, Neil M.; Schwartzberg, Lee; Spitler, Lynn E.; Garfield, David H.; O'Connor, Audrey A.; Nayak, Shankar K.

In: Critical Reviews in Oncology/Hematology, Vol. 39, No. 1-2, 04.07.2001, p. 115-123.

Research output: Contribution to journalArticle

Dillman, Robert O. ; DeLeon, Cristina ; Beutel, Linda D. ; Barth, Neil M. ; Schwartzberg, Lee ; Spitler, Lynn E. ; Garfield, David H. ; O'Connor, Audrey A. ; Nayak, Shankar K. / Short-term autologous tumor cell lines for the active specific immunotherapy of patients with metastatic melanoma. In: Critical Reviews in Oncology/Hematology. 2001 ; Vol. 39, No. 1-2. pp. 115-123.
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AU - Schwartzberg, Lee

AU - Spitler, Lynn E.

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N2 - We established short-term cell lines for 108/170 (64%) patients with metastatic melanoma. Tumor cell numbers were expanded to 108, then cells were irradiated, aliquoted, and cryopreserved for clinical use. Vaccines have been used to treat 69 patients with clinical follow up for 33 who had measurable metastatic disease at the time vaccine therapy was initiated (METS), and 33 who had no evidence of disease (NED) at the time of vaccine therapy following surgical resection of metastases. The protocol called for a baseline test of delayed tumor hypersensitivity (DTH), three weekly injections, a repeat of the DTH test, then monthly injections for an additional 5 months. Objective tumor responses were noted in 3/26 (12%) patients who received a minimum of three vaccinations, one complete, and two partial, with survivals of 36, 46+, and 78+ months. Only 6/64 (9.4%) had a positive DTH (>10 mm) at baseline, including three METS, all of whom progressed within 4 months and died within a year, and three who are still NED after more than 5 years. Conversion of DTH from negative to positive was documented in 18/44 (41%) patients who were tested at week 0 and 4. At a median follow up of greater than 5 years, the median overall survival (OS) was 40 months for 'NED' with a 5-year survival rate of 39%, and 8.6 months with a 5-year survival rate of 10% for 'METS'. The 18 patients who had conversion of their DTH had a median event-free survival (EFS) of 15.8 months and 5-year EFS of 32% compared to 4.2 months and 9% for the 26 non-converters (P=0.012, two-tailed, log-rank test). Among patients who were NED when treatment started, the 12 patients whose DTH converted had a median overall survival of 61.4 months with 5-year survival of 63% compared to 9.7 months and 0% for the 13 non-converters (P=0.0026). This treatment approach is feasible, produces minimal toxicity, and is associated with long-term survival in a significant subset of patients.

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