Oncolytic virotherapy is an active immunotherapy in the treatment of cancer. Rigvir is the first virus approved as an oncolytic cancer treatment. It has been registered for the treatment of melanoma in Latvia since 2004 and is included in the national guidelines for the treatment of melanoma in Latvia, where approximately 75% of melanoma patients are treated with Rigvir. The objective of this study was to describe long-term virotherapy with Rigvir in a patient with stage IV M1c melanoma, a patient with stage IIIA small cell lung cancer, and a patient with stage IV histiocytic sarcoma.
Materials and methods:
The patients were diagnosed at their respective hospital and subsequently approached the International Virotherapy Center. The study has been approved by the local ethics committee. Written consent was obtained from patients for the anonymous publication of material related to them.
Case 1: Melanoma IV M1c
A woman born in 1972 was diagnosed with malignant melanoma in the lumbar paravertebral region, and the tumor was surgically removed in December 2012; The lymph nodes were left intact. Histological examination of the surgical material confirmed the diagnosis of melanoma stage IV M1c cutis dorsi, Clark V, Breslow 8–9 mm, pT4bNxM1c, S-100 antigen positive, human black melanoma antigen 45 (HMB45) positive, Ki-67 index 10 –15%, intratumoral lymphocytic infiltrate with strong CD3 and CD8 membrane staining, with metastasis to the liver and inguinal lymph nodes.
This study presents the successful application of Rigvir in the treatment of advanced melanoma, small cell lung cancer and histiocytic sarcoma, suggesting the potential of Rigvir as a promising therapeutic option in a variety of cancer types.
Case 2: Stage IIIA small cell lung cancer
A man born in 1934, a long-term and still active smoker with no comorbidities, presented with shortness of breath, dyspnea, and cough, and was diagnosed with right upper lobe small cell lung cancer (pT2N2M0) in May 2009. Metastases were found in the thoracic mediastinal lymph nodes. Fiber bronchoscopy showed enlarged lymph nodes in the right lung. Cytological examination of lymph node biopsy specimens showed poorly differentiated small cell lung cancer; The patient was diagnosed with small cell lung cancer by two cytologists.
The patient has been treated with Rigvir since June 2009, and treatment continues. For the first month, Larifan was also prescribed weekly; The patient has not received any other concomitant treatment.
Lymphocyte subpopulations were measured in blood samples taken in June 2009 and June 2016. In comparison, levels of natural killer cells (CD16+ and CD56+), CD4+, and the ratio of T helpers CD4+/T suppressors CD8+ were normalized. CD3+, CD8+, CD19+, and CD45+ levels were within the reference range.
Comparison of CT scans shows that the diameter of the enlarged pulmonary lymph nodes decreased in size and subsequently normalized.
No serum clinical parameter values above grade 1 according to NCI CTCAE 23 were observed.
Therefore, the patient's condition has improved and has remained stable since October 2009.
Case 3: Histiocytic sarcoma IV
A man born in 1970 had pain on the right side of his abdomen, fever, and had lost about 10 kg of body weight in a short period of time. Histology of lymph node biopsy specimens from the left side of the neck in October 2009 shows a characteristic histiocytic sarcoma. Biopsy samples were positive for the specific markers CD68, CD163, and lysozyme, as well as for CD8, CD43, S-100 antigen, and leukocyte common antigen (LCA). The Ki-67 index was 80%; The cells were negative for cytokeratin AE1/AE3, epithelial membrane antigen (EMA), CD4, CD56, and HMB45, as determined by immunohistochemistry.
The patient has not undergone surgery. In October 2009, he was prescribed symptomatic treatment. Rigvir has been administered on average every 3 weeks for 6 years, except for two interruptions, and treatment continues.
In the fall of 2011, the patient was referred by the Virotherapy Center to the Cancer Center for a medical examination. He then received radiation therapy to the neck lymph nodes, para-aortic and iliac lymph nodes, and mediastinum, along with 6 courses of doxorubicin and cyclophosphamide. At the Cancer Center, he has also been receiving Helixor P for some time in addition to Rigvir.
Lymphocyte subpopulations were measured in blood samples taken in November 2009 and June 2016. In comparison, the levels of CD3+ (absolute count), CD4+ (absolute and relative count), and the ratio of T helpers CD4+/T suppressors CD8+ they decreased. The levels of CD3+ (relative value), natural killer cells (CD16+ and CD56+), CD8+, CD19+, and CD45+ were within the reference range.
The size of the lymph nodes in the abdomen, neck, and chest has decreased.
Summary:
Three patients with stage IV M1c melanoma, stage IIIA small cell lung cancer and stage IV histiocytic sarcoma have been treated long-term with Rigvir virotherapy for 3.5, 7.0 and 6.6 years, respectively. Despite the low survival rates expected for these cancers, patients have shown remarkable prolonged survival and disease stability. In particular, the patient with histiocytic sarcoma has experienced a significant slowing of disease progression, suggesting a potential benefit of treatment with Rigvir in this rare pathology.
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