LDH correlation with survival in advanced melanoma from two large, randomised trials (Oblimersen GM301 and EORTC 18951)

Agarwala, Sanjiv S.; Keilholz, Ulrich; Gilles, E; Bedikian, Agop Y.; Wu, Jane; Kay, Richard; Stein, C. A.; Itri, Loretta M.; Suciu, Stefan; Eggermont, Alexander M.M.

doi:10.1016/j.ejca.2009.04.016

Cited by 125 publications

(105 citation statements)

References 25 publications

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“…Other published TIL ACT trials did not find this correlation (12,14,15). Elevated serum level of lactate dehydrogenase (LDH), a marker of disease activity and tumor burden (21,22) was negatively correlated with clinical response (P ¼ 0.013; 0.219 OR; 95% CI: 0.061-0.992).…”

Section: Intent-to-treat Analysismentioning

confidence: 90%

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 Altogether 23 patients were withdrawn from the study mainly due to clinical deterioration during TIL preparation.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: Intent-to-treat Analysismentioning

confidence: 90%

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

View full text Add to dashboard Cite

show abstract

“…Analysis of two large randomized trials in patients with advanced melanoma also showed a correlation between rising serum LDH levels (even when within normal limits) and poorer survival (Oblimersen GM301 [n = 760], EORTC 18951 [n = 325]) [447].…”

Section: Ldhmentioning

confidence: 99%

Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”

Pflugfelder

Kochs

Blum

et al. 2013

J Deutsche Derma Gesell

181

148

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“…A recent randomized study examining the efficacy of dacarbazine with and without oblimersen in patients with advanced melanoma found that the addition of oblimersen resulted in an improvement in overall response rate and survival, and LDH was found to be highly predictive of the effect of oblimersen. 9 This finding has implications for clinical trials because if patients are not stratified by their LDH level, those with high baseline LDH levels can obscure a treatment effect. S100B PROTEINS S100 proteins are small, acidic molecules that have been implicated in a variety of cellular functions.…”

Section: Lactate Dehydrogenasementioning

confidence: 99%