Ipilimumab/nivolumab/pembrolizumab/talimogene laherparepvec

Abstract

Various toxicities and lack of efficacy: 3 case reports In a retrospective study of 20 women, treated between January 2007 and September 2020, 3 women [ages not stated] were described, who developed immune-mediated hepatitis, immune-mediated colitis, Addison’s disease, immune-mediated pneumonitis or immune-mediated hypophysitis during treatment with ipilimumab/nivolumab or pembrolizumab for lower genital tract melanoma (LGTM). Out of these 3 women, one woman additionally exhibited lack of efficacy while receiving treatment with talimogene laherparepvec for LGTM [dosages, durations of treatments to reactions onsets and outcomes not stated; not all routes stated]. Patient 2: A woman developed immune-mediated hepatitis during treatment with ipilimumab/nivolumab. The woman was diagnosed with LGTM (anovaginal melanoma) with liver metastases according to a stage IV disease. Therefore, she received first-line immunotherapy with 4 cycles of ipilimumab/nivolumab. However, she developed immune-mediated hepatitis secondary to the ipilimumab/nivolumab therapy. Therefore, her therapy with ipilimumab/nivolumab was discontinued. As there was only locoregional disease progression and severe dyschezia, she received palliative radiotherapy for the anovaginal region along with 7 cycles of pembrolizumab. Due to a hepatic progression, ipilimumab/nivolumab therapy was restarted. However, she again developed immune-mediated hepatitis secondary to the ipilimumab/nivolumab therapy. Therefore, her therapy with ipilimumab/ nivolumab was discontinued. Subsequently, her condition progressed locally. Therefore, she received talimogene laherparepvec [TVEC] without remarkable tumour regression. Due to further local and hepatic progression, pembrolizumab therapy was restarted and tumour embolisation for palliation was started. Patient 3: A woman developed immune-mediated colitis, immune-mediated hepatitis and Addison’s disease during treatment with ipilimumab/nivolumab. Additionally, she exhibited lack of efficacy while receiving treatment with talimogene laherparepvec for LGTM. The woman, who had LGTM, received treatment with 12 injections of intratumoural talimogene laherparepvec [T-VEC] due to local vaginal progression; however, her nodal disease was stable after 8 months of pembrolizumab therapy. With talimogene laherparepvec therapy, the local tumour decreased significantly. The third and fourth progression was treated with pembrolizumab and imatinib therapy, respectively for a druggable c-Kit mutation. Due to a new local progression of LGTM, her therapy with intratumoural talimogene laherparepvec injection was restarted without benefit. Thus, lack of efficacy with talimogene laherparepvec was considered. She then received ipilimumab/nivolumab along with palliative percutaneous radiotherapy, which successfully stopped local progression. However, she developed immune-mediated colitis, hepatitis and Addison’s disease secondary to the ipilimumab/nivolumab therapy. Therefore, her therapy with ipilimumab/nivolumab was discontinued after 4 cycles. At the time of report, her therapy with ipilimumab/nivolumab was not restarted. Patient 5: A woman developed immune-mediated pneumonitis and immune-mediated hypophysitis during treatment with pembrolizumab and ipilimumab/nivolumab. The woman had a superficially spreading LGTM (vulvar melanoma) with ulcerations according to a stage IIIc disease and an infiltration depth of 6mm. At the time of initial diagnosis, she underwent a dorsal hemivulvectomy, partial colpectomy and inguinal sentinel lymphadenectomy. After 11 months, she relapsed for the first time and was treated with a pelvic exenteration. Due to systemic metastases in the lung, liver and pleura, she was treated with one cycle of pembrolizumab and 3 cycles of ipilimumab/nivolumab 7 months later. However, she developed immune-mediated pneumonitis and immune-mediated hypophysitis secondary to the pembrolizumab and ipilimumab/nivolumab therapy. Therefore, pembrolizumab and ipilimumab/nivolumab therapy were stopped. Despite therapy discontinuation, a prolonged response was observed on follow-up. At the time of the report, she had not received any further therapy, and her LGTM remained stable for 38 months.