Clinical responses and lymphoid infiltrates in metastatic melanoma following treatment with intralesional GM-CSF

Si, Zhaoyi; Hersey, Peter; Coates, Alan S.

doi:10.1097/00008390-199606000-00008

Cited by 95 publications

(42 citation statements)

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“…The need for CD4 + lymphocytes to infiltrate the tumours in order to make the treatment successful agrees well with reports from other groups on the importance of tumour-infiltrating lymphocytes in primary and metastatic melanoma (Clark et al, 1989; Clemente et al, 1996;Mihm et al, 1996;Zehntner et al, 1999;Hernberg et al, 1997;Si et al, 1996). CD4 + lymphocytes generally have been considered to be immunoregulatory but have, in recent years, also been found to have a direct cytotoxic activity (Thomas and Hersey, 1998).…”

Section: Discussionsupporting

confidence: 86%

“…Our group has previously shown the importance of CD4 + lymphocytes in melanoma metastases for response to IFN-α treatment (Håkansson et al, 1996). With granulocyte macrophage colony stimulating factor (GM-CSF) treatment, responding patients showed marked increases and high absolute numbers of T-cell infiltrates into the tumour, particularly of the CD4 T-cell subset (Si et al, 1996). This also concurs well with preliminary data from Zehnenter et al (1999) suggesting that T-cell infiltration is associated with clinical response to melanoma immunotherapy.…”

mentioning

confidence: 99%

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Biochemotherapy of metastatic malignant melanoma. Predictive value of tumour-infiltrating lymphocytes

Håkansson

Gustafsson²,

Krysander

et al. 2001

Br J Cancer

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SummaryThe therapeutic efficacy of biochemotherapy in metastatic malignant melanoma still carries a low remission rate, but with some durable responses. It would therefore be of considerable importance if patients with a high probability of responding could be identified using predictive tests. The response to interferon-alpha (IFN-α) correlates with the occurrence of CD4 + lymphocytes identified by fine-needle aspirates from melanoma metastases (Håkansson et al, 1996). The present investigation studies a possible correlation between tumourinfiltrating CD4 + lymphocytes in malignant melanoma metastases and the therapeutic effect of biochemotherapy. A total of 25 patients with systemic and 16 with regional metastatic melanoma were analysed before initiation of biochemotherapy (cis-platinum 30 mg/m 2 d.1-3, DTIC 250 mg/m 2 d.1-3 i.v. and IFN-α2b 10 million IU s.c. 3 days a week, q. 28d.). A monoclonal antibody, anti-CD4, was used to identify tumourinfiltrating lymphocytes in fine-needle aspirates before start of treatment. The presence of these lymphocytes was correlated to response, time to progression and overall survival. A statistically significant correlation (P = 0.01) was found between the occurrence of CD4 + lymphocytes and tumour regression during biochemotherapy in patients with systemic disease. Out of 14 patients with moderate to high numbers of infiltrating CD4 + lymphocytes, 12 achieved tumour regression. In contrast, among patients with low numbers of these cells in metastatic lesions, 8 out of 11 had progressive disease. We also found a significantly longer time to progression (P < 0.003) and overall survival (P < 0.01) among patients with moderate to high numbers of these cells compared to patients with low numbers of these cells before initiation of biochemotherapy. Furthermore, in patients with regional disease, we found a significantly longer time to progression (P = 0.01) and a trend toward a longer overall survival time (P = 0.09). Based on these results and as previously shown with IFN-α therapy alone, there seems to be a need for CD4 + lymphocytes infiltrating the tumours before the start of biochemotherapy to make the treatment successful. Determination of these cells in fine-needle aspirates seems to be a method to predict responders to biochemotherapy, thus increasing the cost-benefit of this treatment strategy considerably, both in terms of patient adverse reactions and health care costs. The aim of the present investigation was therefore to study whether the presence of tumour-infiltrating CD4 + lymphocytes identified by fine-needle aspirates of melanoma metastases before treatment is started also correlates with the response to biochemotherapy. MATERIALS AND METHODS Study populationThis report describes 41 patients with metastatic malignant melanoma, 26 males and 15 females. The median age was 61 years (range 36-77) and Karnofsky performance status was 70 or more. Recurrences were cytologically verified by fine-needle aspirates before start of treatment. Two groups of patients were st...

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Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 99%

Biochemotherapy of metastatic malignant melanoma. Predictive value of tumour-infiltrating lymphocytes

Håkansson

Gustafsson²,

Krysander

et al. 2001

Br J Cancer

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“…The need for CD4 + lymphocytes to infiltrate the tumours in order to make the treatment successful agrees well with reports from other groups on the importance of tumour-infiltrating lymphocytes in primary and metastatic melanoma (Clark et al, Overall survival in patients with regional disease according to the number of tumour-infiltrating CD4 + lymphocytes before initiation of biochemotherapy, P = 0.09 1989; Clemente et al, 1996;Mihm et al, 1996;Zehntner et al, 1999;Hernberg et al, 1997;Si et al, 1996). CD4 + lymphocytes generally have been considered to be immunoregulatory but have, in recent years, also been found to have a direct cytotoxic activity (Thomas and Hersey, 1998).…”

Section: Discussionsupporting

confidence: 86%

True

2001

Br J Cancer

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“…[98][99][100][101] These studies and others led to the development of T-VEC, an agent that uses a modified herpes simplex virus to induce tumor cell lysis and to deliver localized expression of GM-CSF to injected lesions. 102 A recent phase 3 trial in select patients with unresectable stage IIIB-IV melanoma randomized subjects to intralesional injection of T-VEC versus subcutaneous injection of GM-CSF.…”

Section: Talimogene Laherparepvec (T-vec)mentioning

confidence: 99%

Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology

Coit¹,

Thompson²,

Algazi³

et al. 2016

J Natl Compr Canc Netw

218

167

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OverviewIn 2016, an estimated 76,380 patients will be diagnosed with and approximately 10,130 patients will die of melanoma in the United States.1 However, these figures for new cases may represent a substantial underestimate, as many superficial and in situ melanomas treated in the outpatient setting are not reported. The incidence of melanoma continues to increase dramatically, at an overall rate of 33% for men and 23% women from 2002 to 2006.2 Melanoma is increasing in men more rapidly than any other malignancy, and in women more rapidly than any other malignancy except lung cancer. AbstractThis selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Melanoma focuses on adjuvant therapy and treatment of in-transit disease, because substantial changes were made to the recommendations for the 2016 update. Depending on the stage of the disease, options for adjuvant therapy now include biochemotherapy and highdose ipilimumab. Treatment options for in-transit disease now include intralesional injection with talimogene laherparepvec (T-VEC), a new immunotherapy. These additions prompted reassessment of the data supporting older recommended treatment options for adjuvant therapy and in-transit disease, resulting in extensive revisions to the supporting discussion sections. J Natl Compr Canc Netw 2016;14(4):450-473 NCCN Categories of Evidence and ConsensusCategory 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.All recommendations are category 2A unless otherwise noted.Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Please NoteThe NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ® ) are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines ® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network ® (NCCN ® ) makes no representation or warranties of any kind regarding their content, use, or application and disclaims any responsibility for their applications or use in any way. The full NCCN Guidelines for Melanoma are not printed in this issue of JNCCN but can be accessed online at NCCN.org.© National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. Disclosures for the NCCN Melanoma ...

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Clinical responses and lymphoid infiltrates in metastatic melanoma following treatment with intralesional GM-CSF

Cited by 95 publications

References 0 publications

Biochemotherapy of metastatic malignant melanoma. Predictive value of tumour-infiltrating lymphocytes

Biochemotherapy of metastatic malignant melanoma. Predictive value of tumour-infiltrating lymphocytes

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Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology

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