Prognostic Factors That Determine the Long-Term Survival of Patients with Unresectable Metastatic Melanoma

Bedikian, Agop Y.; Johnson, Marcella M.; Warneke, Carla L.; Papadopoulos, Nicholas E.; Kim, Kevin; Hwu, Wen Jen; McIntyre, Susan; Hwu, Patrick

doi:10.1080/07357900802027073

Cited by 72 publications

(43 citation statements)

References 39 publications

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“…Furthermore, we applied TIL immunotherapy to a highly advanced patient group, as 80% of the enrolled or treated patients had M1c disease. Notably, 30% of the treated patients with M1c disease responded to therapy, including patients with brain metastases, indicating that TIL ACT is an effective treatment for this unfavorable patient group (23,24). The overall objective response rate was 29% among enrolled patients and 40% in the evaluated patient population.…”

Section: Discussionmentioning

confidence: 84%

Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma: Intent-to-Treat Analysis and Efficacy after Failure to Prior Immunotherapies

Besser

Shapira‐Frommer

Itzhaki

et al. 2013

Clinical Cancer Research

340

279

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Purpose: Adoptive cell transfer (ACT) using autologous tumor-infiltrating lymphocytes (TIL) was reported to yield objective responses in about 50% of metastatic patients with melanoma. Here, we present the intent-to-treat analysis of TIL ACT and analyze parameters predictive to response as well as the impact of other immunotherapies.Experimental Design: Eighty patients with stage IV melanoma were enrolled, of which 57 were treated with unselected/young TIL and high-dose interleukin-2 (IL-2) following nonmyeloablative lymphodepleting conditioning.Results: TIL cultures were established from 72 of 80 enrolled patients. Altogether 23 patients were withdrawn from the study mainly due to clinical deterioration during TIL preparation. The overall response rate and median survival was 29% and 9.8 months for enrolled patients and 40% and 15.2 months for treated patients. Five patients achieved complete and 18 partial remission. All complete responders are on unmaintained remission after a median follow-up of 28 months and the 3-year survival of responding patients was 78%. Multivariate analysis revealed blood lactate-dehydrogenase levels, gender, days of TIL in culture, and the total number of infused CD8 þ cells as independent predictive markers for clinical outcome.Thirty-two patients received the CTLA-4-blocking antibody ipilimumab prior or post TIL infusion. Retrospective analysis revealed that nonresponders to ipilimumab or IL-2 based therapy had the same overall response rate to ACT as other patients receiving TIL. No additional toxicities to TIL therapy occurred following ipilimumab treatment. Conclusion: Adoptive transfer of TIL can yield durable and complete responses in patients with refractory melanoma, even when other immunotherapies have failed.

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Section: Discussionmentioning

confidence: 84%

Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma: Intent-to-Treat Analysis and Efficacy after Failure to Prior Immunotherapies

Besser

Shapira‐Frommer

Itzhaki

et al. 2013

Clinical Cancer Research

340

279

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“…In addition, 7 (47%) responders had elevated baseline LDH levels. Thus, these data suggest that elevation of LDH does not bias against response as has been suggested for chemotherapy with DTIC and other agents (29). Therefore, recent trends to exclude patients from trials based on elevations of LDH do not appear to be appropriate for studies of biologic agents such as the CTLA4-blocking antibody tremelimumab.…”

Section: Discussionmentioning

confidence: 88%

Phase II Trial of Tremelimumab (CP-675,206) in Patients with Advanced Refractory or Relapsed Melanoma

Kirkwood

Lorigan

Hersey

et al. 2010

Clinical Cancer Research

219

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Purpose: This phase II study assessed the antitumor activity of tremelimumab, a fully human, anti-CTL-associated antigen 4 monoclonal antibody, in patients with melanoma.Experimental Design: Patients with refractory/relapsed melanoma received 15 mg/kg tremelimumab every 90 days. After 4 doses, patients with tumor response or stable disease were eligible to receive ≤4 additional doses. Primary endpoint was best overall tumor response assessed by an independent endpoint review committee, and secondary endpoints included duration of response, overall survival, progression-free survival, and safety.Results: Of 251 patients enrolled, 246 (241 response-evaluable) received tremelimumab. Objective response rate was 6.6% (16 partial responses); duration of response was 8.9 to 29.8 months. Eight (50%) objective responses occurred in patients with stage IV M 1c disease, and 11 (69%) were ongoing at last tumor assessment. Eight (3.3%) patients achieved responses in target lesions (Response Evaluation Criteria in Solid Tumors) despite progressive disease within the first cycle. All 8 survived for >20 months; 5 (63%) remained alive. Clinical benefit rate (overall response + stable disease) was 21% (16 partial responses and 35 stable disease), and median overall survival was 10.0 months. Progression-free survival at 6 months was 15%, and survival was 40.3% at 12 months and 22% at 24 months. Common treatmentrelated adverse events were generally mild to moderate, and grade 3/4 adverse events included diarrhea (n = 28, 11%), fatigue (n = 6, 2%), and colitis (n = 9, 4%). There were 2 (0.8%) treatment-related deaths.Conclusions: Tremelimumab showed an objective response rate of 6.6%, with all responses being durable ≥170 days since enrollment, suggesting a potential role for tremelimumab in melanoma.

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“…Indeed, the reported 5-year survival rates for MM ranged from 20-35% Hancock et al, 2004). Local control of a tumor seemed not to be a strong predictor of the survival of melanoma patients (Hancock et al, 2004), whereas the comprehensive treatment consisting of local surgical treatment, systemic biological treatment, chemotherapy, and targeted therapy allowed for an overall clinical benefit for these patients (Morton et al, 1999;Bedikian et al, 2008;Shiga et al, 2012;Min et al, 2014). However, despite all these improvements and ongoing research, the prognosis of MM is still poor and an effective treatment remains elusive.…”

Section: Discussionmentioning

confidence: 99%

Interferon-α-2b as an adjuvant therapy prolongs survival of patients with previously resected oral muscosal melanoma

Wang¹,

Jing²,

Lv³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Two major subtypes of melanoma include cutaneous melanoma and mucosal melanoma. The latter type is rare and usually occurs in the head and neck region. High-dose interferon-a-2b (IFNa-2b) has proven effective in the treatment of cutaneous melanoma. Recently, a regimen of temozolomide plus cisplatin was reported more likely to improve relapse-free survival and overall survival than high-dose IFN-a-2b for mucosal melanoma. We conducted this study to analyze the therapeutic effect of high-dose IFN-a-2b for patients with oral mucosal melanoma who had received prior chemotherapy. One hundred and seventeen patients with stage III-IVa oral mucosal melanoma who had received chemotherapy were analyzed. The overall survival and relapse-free survival were compared between the patients with/without high-dose IFN-a-2b. The results indicate that the IFN-a-11945 IFN-α-2b adjuvant therapy for melanoma prolongs survival ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 11944-11954 (2015) 2b treatment group had a longer relapse-free survival rate (P = 0.0169) as compared to the control group. However, the overall survival was not significant between the two groups (P = 0.096), except in patients in stage IVa, whose overall survival increased by 20 months (P = 0.0146). The adverse reactions included a drug-induced influenza-like syndrome, gastrointestinal responses, myelosuppression, and hepatoxicity, which were predominantly of grade 1-2 and reversible. Thus, patients with resected oral mucosal melanoma, even those who have received chemotherapy, could benefit from the treatment of high-dose IFN-a-2b.

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Prognostic Factors That Determine the Long-Term Survival of Patients with Unresectable Metastatic Melanoma

Cited by 72 publications

References 39 publications

Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma: Intent-to-Treat Analysis and Efficacy after Failure to Prior Immunotherapies

Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma: Intent-to-Treat Analysis and Efficacy after Failure to Prior Immunotherapies

Phase II Trial of Tremelimumab (CP-675,206) in Patients with Advanced Refractory or Relapsed Melanoma

Interferon-α-2b as an adjuvant therapy prolongs survival of patients with previously resected oral muscosal melanoma

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