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
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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.
KeywordsNivolumab PD-1 Melanoma Lactate dehydrogenase CheckMate-066
Expanded access program
Eastern Cooperative Oncology Group
Immune-related adverse events
Upper limit of normal
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.
- 7.Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD et al (2015) Efficacy and safety in key patient subgroups of nivolumab alone or combined with ipilimumab versus ipilimumab alone in treatment-naïve patients with advanced melanoma (CheckMate 067). European Society for Medical Oncology 2015 Congress. Presented September 28, 2015Google Scholar
- 16.Larkin J, D’Angelo SP, Sosman JA, Lebbe C, Brady B, Neyens B et al (2015) Efficacy and safety of nivolumab alone or in combination with ipilimumab in the treatment of advanced mucosal melanoma. Society for Melanoma Research 2015 Congress. Presented November 20, 2015Google Scholar
- 17.Atkinson V, Ascierto PA, Long GV, Brady B, Dutriaux C, Maio M et al (2015) Two-year survival and safety update in patients with treatment-naïve advanced melanoma (MEL) receiving nivolumab or dacarbazine in CheckMate 066. Presented at Society for Melanoma Research (SMR) 2015 International Congress, November 18–21, San Francisco, California, USAGoogle Scholar
- 19.Kelderman S, Heemskerk B, van Tinteren H, van den Brom RR, Hospers GA, van den Eertwegh AJ, Kapiteijn EW, de Groot JW, Soetekouw P, Jansen RL, Fiets E, Furness AJ, Renn A, Krzystanek M, Szallasi Z, Lorigan P, Gore ME, Schumacher TN, Haanen JB, Larkin JM, Blank CU (2014) Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma. Cancer Immunol Immunother 63(5):449–458PubMedGoogle Scholar