Patient with Generalized Melanoma Treated with Nivolumab with Long-Term Response after Previous Failure of Combined Chemoimmunotherapy

Case Description

In May 2015, a 68-year-old female patient was examined at the dermato-oncology outpatient clinic of our hospital. She had been undergoing treatment for ulcerative colitis and hypothyroidism. The patient was referred for examination after a narrow excision of malignant melanoma. She first noticed a pigmented lesion on her back between the shoulder blades about 5 years before the excision. The patient reported that initially it was flat, later it became raised, and in the last 2 months before excision, it became wet and bled. A narrow excision was performed at the surgery department of her residence. Histology revealed secondary nodular malignant melanoma Breslow 1.8, Cl IV, no ulceration described, and as many as 25 mitoses per 1 mm2. Following examination at our outpatient clinic, an excision of the scar with a 1.5 cm margin was indicated, along with sentinel lymph node mapping. The operation was conducted on June 8, 2015, at the 1st Surgical Clinic with the patient hospitalized at our department. The histology of the excised scar revealed small foci of extramurally diagnosed melanoma, invasion depth 1.7. Sentinel lymph node from the left axilla showed metastasis of malignant melanoma. Subsequently, on July 10, 2015, exenteration of the left axilla was performed, removing 12 lymph nodes, all without metastatic involvement. Given the positivity of the sentinel node, adjuvant immunotherapy with interferon-alpha standard dosing 10 million units subcutaneously three times weekly after an induction phase where application was 5 times weekly for one month was initiated on August 10, 2015. The therapy was concluded on August 4, 2016.

During the follow-up visit on December 7, 2016, a resistance in the subcutaneous area of the scar was diagnosed—histologically identified as a melanoma metastasis. CT scans of the chest, abdomen, and pelvis showed no further tumor spread, and the patient continued to be monitored. On November 6, 2017, she was examined again, and several livid, firm, confluent subcutaneous resistances were detected in the scar area on her back. We attempted to include the patient in the AMGEN MASTERY 265 study, but ulcerative colitis was an exclusion criterion. Therefore, we examined for BRAF mutation, which was negative, and on December 15, 2017, performed a PET/CT concluding with a hypermetabolic focus in the left subcutaneous area of the back. The oncology probability scale was 5 - positive finding. Mediastinal lymphadenopathy. The oncology probability scale was 5 - positive finding. On December 17, 2017, combined chemoimmunotherapy was initiated with Vinblastine, DTIC cyclophosphamide, and Roferon 6 million units subcutaneously three times weekly.

On March 21, 2018, the patient had a CT scan of the chest, abdomen, and pelvis concluding with: new small lung lesion suspected of metastatic etiology, subcutaneous mass progressing in size, and roughly stationary mediastinal lymphadenopathy. After 4 cycles, chemotherapy was stopped on March 27, 2018, due to disease progression in the left shoulder blade area, and the patient was scheduled for actinotherapy from May 14 to May 23, targeting a dose of 32 Gy. Actinotherapy had a mild effect. Due to further progression, we requested the approval of Opdivo therapy under paragraph 16, and the insurance approved the treatment.

The Opdivo therapy 480 mg every 4 weeks started on July 3, 2018. After 3 doses of Opdivo, a control CT was performed, concluding partial regression of the lesion behind the left shoulder blade, with new changes described in the lung parenchyma with hilar and mediastinal lymphadenopathy, unable to distinguish between inflammatory changes with reactive lymphadenopathy and metastatic involvement—hence further monitoring was required. Based on the CT image, we leaned more towards an inflammatory picture and evaluated the treatment effect as a partial response, recommending continuation of therapy. On September 17, 2018, the continuation of Opdivo treatment was approved—control CT on October 24, 2018, after the 5th dose, concluded stationary image of multiple nodules in the lung parenchyma and mediastinal and hilar lymphadenopathy. A section of haziness in the scarring changes of the dorsal left subcutaneous tissue on the chest today rather with mild regression. The image is evaluated as a partial response, recommending continuation of Opdivo 480 mg intravenous every 4 weeks. CT examination after the 8th dose of Opdivo on February 8, 2019—findings of mediastinal lymphadenopathy improved, with still present but reduced node packets pretracheal and tracheal. For example, the right pretracheal node previously 16 x 15 mm, now 12 x 11 mm, right hilar node previously 19 x 13 mm, now 16 x 12 mm, subcarinal node previously 38 x 18 mm, now 36 x 15 mm.

We continue the therapy; the patient is in very good clinical condition, tolerating the treatment well.

MUDr. Taťána Šuková

Department of Dermatovenereology, VFN and 1st Faculty of Medicine, Charles University, Prague