Cancer Immunology, Immunotherapy

, Volume 65, Issue 11, pp 1395–1400 | Cite as

Complete response to nivolumab monotherapy in a treatment-naive, BRAF wild-type patient with advanced mucosal melanoma and elevated lactate dehydrogenase: a case report from a phase III trial

  • Paolo A. Ascierto
  • Vito Vanella
  • Antonio Maria Grimaldi
  • Festino Lucia
  • Marco Palla
  • Ester Simeone
  • Nicola Mozzillo
Original Article


The anti-PD-1 agent, nivolumab, has been approved both as monotherapy and in combination with ipilimumab for the treatment of unresectable or metastatic melanoma in the USA and European Union. Here we present the case of a patient with treatment-naive, metastatic mucosal melanoma and baseline LDH approximately seven times the upper limit of normal. The patient was enrolled in a clinical trial (CheckMate 066) and achieved a partial response, followed by a durable complete response with nivolumab treatment. The patient’s LDH levels were documented in each cycle and dropped markedly within 2 months, when partial response to treatment was already evident. LDH levels remained low for the rest of follow-up, consistent with the ongoing complete response to treatment. The patient experienced only mild immune-related adverse events (grade 1–2), which included vitiligo and rash. This exceptional response suggests that patients with high LDH levels at baseline should be considered for nivolumab treatment. LDH levels, however, should not serve as a predictive marker of response to nivolumab. Moreover, this case suggests the need to identify patients who will achieve the greatest benefit from nivolumab monotherapy.


Nivolumab PD-1 Melanoma Lactate dehydrogenase CheckMate-066 



Alkaline phosphatase


Alanine aminotransferase


Aspartate aminotransferase


Complete response


Expanded access program


Eastern Cooperative Oncology Group




Immune-related adverse events


Not applicable


Partial response


Performance status


Ursodeoxycholic acid


Upper limit of normal


Wild type



Professional medical writing assistance was provided by Dan Rigotti, PhD, at StemScientific, an Ashfield Company, and was funded by Bristol-Myers Squibb.


The parent clinical trial (CheckMate 066) was funded by Bristol-Myers Squibb.

Compliance with ethical standards

Conflict of interest

Paolo A. Ascierto has/had a consultant/advisory role for Bristol-Myers Squibb, Roche-Genentech, MSD, Novartis, Ventana, Amgen, Array. He received also research funds from Bristol-Myers Squibb, Roche-Genentech, Ventana. The remaining authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Paolo A. Ascierto
    • 1
  • Vito Vanella
    • 1
  • Antonio Maria Grimaldi
    • 1
  • Festino Lucia
    • 1
  • Marco Palla
    • 1
  • Ester Simeone
    • 1
  • Nicola Mozzillo
    • 1
  1. 1.Istituto Nazionale Tumori Fondazione “G. Pascale”NaplesItaly

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