Resolution of Melanoma to Programmed Death-1 Blockade but Simultaneous Rapid Progression of Concomitant Chronic Lymphocytic Leukemia

Acta Haematol. 2023;146(2):166-171. doi: 10.1159/000527631. Epub 2022 Oct 21.

Abstract

Here, we present a novel case of a patient with chronic lymphocytic leukemia (CLL) who received CTLA-4 and then PD-1 immune-checkpoint blockade (ICB) as treatment for concomitant metastatic melanoma. Whereas the metastatic melanoma was responsive to ICB, the CLL rapidly progressed (but responded to ICB cessation and ibrutinib). There were no new genetic mutational drivers to explain the altered clinical course. PD-1/PD-L1/PD-L2 and CTLA-4/CD80/CD86 expression was not increased in CLL B cells, CD8+ or CD4+ T-cell subsets, or monocytes. The patient's CLL B cells demonstrated strikingly prolonged in vitro survival during PD-1 blockade, which was not observed in samples taken before or after ICB, or with other patients. To our knowledge, a discordant clinical course to ICB coupled with these biological features has not been reported in a patient with dual malignancies.

Keywords: CLL; Immune-checkpoint blockade; Metastatic melanoma.

Publication types

  • Case Reports

MeSH terms

  • Antineoplastic Agents* / immunology
  • Antineoplastic Agents* / therapeutic use
  • B7-H1 Antigen
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / immunology
  • Disease Progression
  • Humans
  • Immune Checkpoint Inhibitors* / immunology
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell* / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell* / pathology
  • Melanoma* / drug therapy
  • Melanoma* / etiology
  • Melanoma* / pathology
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor* / immunology
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / etiology
  • Skin Neoplasms* / pathology

Substances

  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor
  • B7-H1 Antigen
  • PDCD1 protein, human
  • Immune Checkpoint Inhibitors
  • ibrutinib
  • Antineoplastic Agents