CLL/SLL

Published case study – pembrolizumab to treat a patient with both Chronic Lymphocytic Leukemia and Metastatic Melanoma

On 22nd August 2017, in a Letter to the Editor of the Journal of the European Academy of Dermatology and Venereology, M. Arenbergerova from Charles University, Prague, Czech Republic, et al. published a case report of male patient, 49 years of age, diagnosed in 2014 with atypical, CD23 negative, Rai stage II B-cell Chronic Lymphocytic Leukemia (CLL). Watch and wait was recommended.

In April 2015, a superficial spreading Melanoma of Breslow was excised from the left eyebrow and classified as stage IIA and with wild-type BRAF. Six months later, the patient experienced progressive left cervical lymphadenopathy and neurological symptoms (tingling of the left side of the body, loss of balance, headache). Thirteen cerebral metastases were identified by MRI and suspected to be due to melanoma progression. Stereotactic radiotherapy was not an option due to the extensive cerebral metastatic disease.

Key Highlights:
  • Histopathological examination of enlarged cervical lymph node identified CLL cell infiltration and dispersed Melanoma metastases around 1–1.5mm in diameter; elevated LDH
  • Systemic therapy with pembrolizumab (2mg/kg every 3 weeks) was initiated
  • Brain MRI after 3 months showed partial response
  • Complete response was observed at 12 months, which lasted for 6 months when on re-biopsy of cervical lymph node CLL infiltrate-free Melanoma metastases were found
  • Follow-up CT found enlarged cervical and axillary lymph nodes had reduced in size by 25%; evaluated as stable disease for CLL
  • Thrombocytopenia observed at 72–85x109/L; all other blood examinations were normal
  • LDH level fell within normal range in the third month of therapy
  • Within the fourth month of therapy, a central longitudinal scalp depigmentation appeared which remained stable up to last follow up
  • Patient is still on pembrolizumab, currently for 21 months

Overall, in response to pembrolizumab, the patient responded with complete response in Melanoma and stable disease in CLL. The thrombocytopenia reported may have been an adverse event of the anti-PD-1 therapy or a symptom of the CLL. The authors concluded by stating that “treatment of patients with cancer duplicities remains challenging.”

Abstract:

Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody against PD-1, has demonstrated antitumor activity and a manageable safety profile in patients with different solid tumors and hematologic malignancies in multiple clinical trials (1-4). Although these data highlight the effectiveness of PD-1 pathway inhibition, some patients, even those with highly immunogenic tumors, such as melanoma, do not achieve objective response (1). An increased association of B-cell chronic lymphocytic leukemia (B-CLL) and melanoma, possibly related to an underlying immunologic defect, has been previously reported (5). We still have limited data on the management of advanced stages of cancer duplicities.

References
  1. Arenbergerova M. et al. Killing two birds with one stone: response to pembrolizumab in a patient with metastatic melanoma and B-cell chronic lymphocytic leukemia. Journal of the European Academy of Dermatology and Venereology. 2017 Aug 22. DOI: 10.1111/jdv.14537. [Epub ahead of print].