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Prognostic and predictive role of elevated lactate dehydrogenase in patients with melanoma treated with immunotherapy and BRAF inhibitors

a systematic review and meta-analysis

Petrelli, Faustoa; Ardito, Raffaelec; Merelli, Barbarad; Lonati, Veronicaa; Cabiddu, Marya; Seghezzi, Silviab; Barni, Sandroa; Ghidini, Antonioe

doi: 10.1097/CMR.0000000000000520
REVIEW ARTICLE

Levels of serum lactate dehydrogenase (LDH) are a recognized prognostic factor in malignant melanoma (MM). It is relevant to confirm its prognostic role in patients treated with targeted therapies [BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi)] and immunotherapy (IT). Furthermore, its role as a predictive marker in patients treated with these drugs had still not been investigated. We performed an electronic search for studies reporting information on overall survival (OS) or progression-free survival (PFS) according to LDH levels and on their predictive effect in patients treated with targeted therapies (BRAFi and MEKi) and IT. Data were pooled using hazard ratios (HRs) for OS and HRs for PFS according to a fixed-effect or a random-effect model. For predictive analysys, effect of new agents versus standard therapy was evaluated in LDH high population. A total of 71 publications were retrieved for a total of 16 159 patients. Overall, elevated LDH levels were associated with an HR for OS of 1.72 [95% confidence interval (CI): 1.6–1.85; P<0.0001]. Similarly, HR for PFS was 1.83 (95% CI: 1.53–2.2; P<0.0001). In the LDH elevated subgroup, new agents improved OS significantly (HR: 0.71; 95% CI: 0.62–0.82; P<0.0001) and PFS (HR: 0.63; 95% CI: 0.55–0.72; P<0.0001). In advanced MM treated with IT or BRAFi±MEKi, elevated LDH level at baseline represents a poor prognostic factor. However, patients with increased LDH levels and treated with these drugs gain significant benefits in terms of PFS and OS.

aOncology Unit

bNuclear Medicine Unit, ASST Bergamo Ovest, Treviglio (BG)

cOncology Day Hospital, IRCCS Centro di Riferimento Oncologico della Basilicata (CROB), Vulture (PZ)

dOncology Unit, ASST Papa Giovanni XXIII, Bergamo

eCasa di cura Igea, Oncology Unit, Milano, Italy

Correspondence to Fausto Petrelli, MD, Oncology Unit, Oncology Department, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy Tel: +39 036 342 4420; fax: +39 036 342 4380; e-mail: faupe@libero.it

Received March 15, 2018

Accepted September 11, 2018

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.