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. 2022 Jul 5;14(13):3282.
doi: 10.3390/cancers14133282.

Development of Lymphopenia during Therapy with Immune Checkpoint Inhibitors Is Associated with Poor Outcome in Metastatic Cutaneous Melanoma

Dirk Tomsitz  1 , Max Schlaak  2 , Sarah Zierold  1 , Giulia Pesch  1 , Thomas U Schulz  1 , Genoveva Müller  1 , Christine Zecha  1 , Lars E French  1   3 , Lucie Heinzerling  1   4
Affiliations

Development of Lymphopenia during Therapy with Immune Checkpoint Inhibitors Is Associated with Poor Outcome in Metastatic Cutaneous Melanoma

Dirk Tomsitz et al. Cancers (Basel). .

Abstract

Predictive markers for immune checkpoint inhibitor (ICI) therapy are needed. Thus, baseline blood counts have been investigated as biomarkers, showing that lymphopenia at the start of therapy with (ICI) is associated with a worse outcome in metastatic melanoma. We investigated the relationship between the occurrence of lymphopenia under ICI and disease outcome. Patients with metastatic melanoma who had undergone therapy with ICI were identified in our database. Only patients with a normal lymphocyte count at baseline were included in this retrospective study. Progression-free survival (PFS) and overall survival (OS) were compared between patients in which lymphopenia occurred during ICI therapy and those who did not develop lymphopenia. In total, 116 patients were analyzed. Lymphopenia occurred in 42.2% of patients, with a mean onset after 17 weeks (range 1-180 weeks). The occurrence of lymphopenia during immunotherapy was significantly associated with a shorter PFS and OS. Patients who developed lymphopenia (n = 49) had a mean PFS of 13.3 months (range 1-67 months) compared to 16.9 months (range 1-73 months) for patients who did not develop lymphopenia (n = 67; p = 0.025). Similarly, patients with lymphopenia had a significantly shorter OS of 28.1 months (range 2-70 months) compared with 36.8 months (range 4-106 months) in patients who did not develop lymphopenia (p = 0.01). Patients with metastatic melanoma who develop lymphopenia during ICI therapy have a worse prognosis with significantly shorter PFS and OS compared with patients who do not develop lymphopenia.

Keywords: immune checkpoint inhibitors; lymphopenia; melanoma; outcome; predictive markers.

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Conflict of interest statement

D.T.: Consultancy, speaker fees or travel grants: BMS, Roche, Novartis, Sanofi, Recordati, Kyowa Kirin, Sun Pharma. M.S.: Consultancy, speaker fees or travel grants: BMS, MSD, Roche, Kyowa Kirin, Novartis, Sanofi Genzyme, Pierre Fabre, Sun Pharma, Immunocore, Recordati. L.H.: Consultancy, speaker fees, travel grants or research funding: BMS, MSD, Merck, Roche, Amgen, Curevac, Novartis, Sanofi, Pierre Fabre, BiomeDx. Clinical studies: BMS, MSD, Merck, Roche, Amgen, GSK, Curevac, Novartis, BiomeDx. S.Z., G.P., T.U.S., G.M., C.Z., L.E.F. declare no conflict of interest.

Figures

Figure 1
Figure 1
PFS and OS. Patients were followed for a minimum of 6 months. Tick marks indicate censored data. Time is given in months. Panels (A,C,E) show the Kaplan–Meier estimates of PFS of patients. Panels (B,D,F) show the Kaplan–Meier estimates of OS. Panel (A): the mean PFS of patients who developed lymphopenia was significantly shorter (13.3 months) compared to patients who did not develop lymphopenia (16.9 months, p = 0.025). Panel (B): the mean OS of patients who developed lymphopenia was significantly shorter (28.1 months) compared to patients who did not develop lymphopenia (36.8 months, p = 0.01). Panel (C): the mean PFS of patients with a NLR ≥ 5 at baseline was longer (16.3 months) compared to patients with a NLR < 5 at baseline (7.3 months, p = 0.11). Panel (D): the mean OS of patients with a NLR ≥ 5 at baseline was longer (33.6 months) compared to patients with a NLR ratio < 5 at baseline (28.8 months, p = 0.48). Panel (E): the mean PFS of patients with a relative eosinophilic count (REC) ≥ 1.5% at baseline was longer (16.9 months) compared to patients with a REC < 1.5% at baseline (13.3 months, p = 0.188). Panel (F): the mean OS of patients with a REC ≥ 1.5% at baseline was longer (34.2 months) compared to patients with a REC < 1.5% at baseline (31.6 months, p = 0.217).
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Grants and funding

This study was funded by the German Federal Ministry of Education and Research (BMBF) as part of the project MelAutim (01ZX1905A), which aims a systems medicine investigation of melanoma and autoimmunity in the context of immune therapies. The funding source had no influence on the design, conduct, analysis and/or report of this research.

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