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In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2. 1994

D J Schwartzentruber, and S S Hom, and R Dadmarz, and D E White, and J R Yannelli, and S M Steinberg, and S A Rosenberg, and S L Topalian
Surgery Branch and Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

OBJECTIVE To correlate in vitro characteristics of tumor-infiltrating lymphocytes (TIL) with clinical response to TIL immunotherapy in patients with metastatic melanoma. METHODS Forty-one melanoma patients undergoing 43 separate treatment courses with TIL and interleukin-2 (IL-2) from December 1990 through November 1992 were studied prospectively. Multiple patient and treatment characteristics were evaluated for response correlates. In addition, TIL were assayed within 7 days of infusion for characteristics such as doubling time, cell-surface phenotype, autologous tumor lysis in 4-hour chromium-51 release assays, and cytokine secretion following autologous tumor stimulation. RESULTS Nine patients experienced complete or partial tumor regressions. Clinical parameters such as age, sex, sites of disease, performance status, and prior therapies were similar in responders and nonresponders. Treatment variables such as the cumulative IL-2 dose and concomitant administration of cyclophosphamide or interferon (IFN)-alpha were not predictive of response, although responders received 33% more TIL. However, statistically significant differences in favor of clinical response were noted for extranodal source of TIL (v lymph node), shorter culture duration (mean, 38 v 47 days), shorter TIL doubling time (2.6 v 3.7 days), greater autologous tumor lysis by TIL (30% v 15%; effector-to-target [E:T], 40:1), and secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) by TIL following autologous tumor stimulation (six of nine responders v eight of 32 nonresponders). CONCLUSIONS The associations of TIL lysis of autologous tumor and younger TIL age with clinical response observed in this study are supportive of previous reports, and these findings will be useful in designing future clinical trials. The new observation correlating GM-CSF secretion by TIL with clinical response is interesting and needs further substantiation.

UI MeSH Term Description Entries
D007167 Immunotherapy Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. Immunotherapies
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008297 Male Males
D008545 Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445) Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D011237 Predictive Value of Tests In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test. Negative Predictive Value,Positive Predictive Value,Predictive Value Of Test,Predictive Values Of Tests,Negative Predictive Values,Positive Predictive Values,Predictive Value, Negative,Predictive Value, Positive
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D016015 Logistic Models Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. Logistic Regression,Logit Models,Models, Logistic,Logistic Model,Logistic Regressions,Logit Model,Model, Logistic,Model, Logit,Models, Logit,Regression, Logistic,Regressions, Logistic

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