Background Metastatic melanoma is an aggressive form of cancer. Largely ineffective, dacarbazine, temozolamide or fotemustine were the only agents used for a long time. The recent development of checkpoint inhibition immunotherapies has changed the treatment paradigm and improved outcomes although response rates still remain moderate. Despite that, subgroups of patients involved in clinical trials have presented significant responses maintained for long periods of time, defined as ‘long survivors’.
Purpose Description of a case of melanoma metastatic long survivor after immunotherapy treatment
Material and methods A 55-year-old man was diagnosed in June 2005 with nodular melanoma IIB-IIC. He initially underwent surgical resection and subsequent adjuvant therapy with high doses of interferon-2αb. In December 2010, metastatic disease was confirmed by the presence of pulmonary nodules; BRAF mutation determination was negative. In this context, the patient was involved in a clinical trial receiving ipilimumab+dacarbazine (cycles 1–4) and dacarbazine monotherapy (cycles 5–8). The patient presented a partial response after the first four cycles, treatment was completed and then he remained under observation. In May 2013, disease progression was observed. After having undergone several extracranial stereotactic radiotherapy sessions, it was decided, in November 2014, to start treatment with pembrolizumab, within its compassionate use access programme.
Results After 4 months of treatment with pembrolizumab, one of the two pulmonary nodules no longer displayed (considered as a partial response). The disease remained stable until February 2016, when progression of disease was detected as growing of already known metastases (RECIST criteria). Evidence of progression led to early discontinuation of treatment. After pembrolizumab interruption, LDH levels increased abruptly, consistent with the rapid progression of the disease. Two more previously scheduled doses were administered and then pembrolizumab was stopped. 2 weeks after immunotherapy finalisation, LDH levels were significantly reduced. 6 months later the disease remains controlled under fotemustine therapy.
Conclusion RECIST criteria might underestimate the therapeutic benefit of immunotherapeutic agents, leading to treatment discontinuation due to pseudoprogression (an increase in total tumour burden later followed by tumour regression). The use of immune related response criteria potentially may prevent premature cessation of treatment and explain why patients with apparent progressive disease by RECIST criteria experience long term survival.
No conflict of interest
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