Chemo-resistant Gestational Trophoblastic Neoplasia and the Use of Immunotherapy: A Case Report and Review of Literature

Abstract

This is the first reported case of the use of immunotherapy in chemo-resistant Gestational Trophoblastic Neoplasia (GTN) in the country. A 41-year-old, Gravida 4 Para 3 (3013) with a diagnosis of GTN, Stage III: WHO risk score of 13 (Choriocarcinoma) was initially managed with 10 cycles of multiple agent Etoposide, Methotrexate, Actinomycin D-Cyclophosphomide and Vincristine (EMACO) and 19 cycles of Etoposide, Cisplatin-Etoposide Methotrexate and Actinomycin D (EP-EMA). With continuous rise in beta human chorionic gonadotropin (ßhCG) levels, the patient was referred to a Trophoblastic Disease Center where there was note of tumor progression to the brain. She was started on third-line salvage chemotherapy of Paclitaxel and Carboplatin (PC) with concomitant whole brain irradiation completing three cycles after which chemoresistance was again diagnosed with increasing hCG titers and increase in the number and size of the pulmonary masses which were deemed unresectable. Immunotherapy was started with Pembrolizumab showing a good response with marked fall in ßhCG levels. The onset of immune-related adverse events (irAEs) caused a marked delay in subsequent cycles of immunotherapy. With management of the irAEs, two more cycles of Pembrolizumab with fifty percent dose reduction were given with corresponding drop in ßhCG levels. However, the patient subsequently developed gram-negative septicemia with possible hematologic malignancy and finally succumbed to massive pulmonary embolism. The case highlights the importance of prompt diagnosis and referral to a Trophoblastic Disease Center and the use of immunotherapy in chemo-resistant GTN.

Keywords: chemo-resistance; choriocarcinoma; gestational trophoblastic neoplasia; immune-related adverse events; pembrolizumab.

Figure 1

(A) EMACO cycles; (B) EP/EMA cycles. *EP was omitted in the 2^nd cycle; **EP/EMA cycles VIII, XI-XIV, XVII-XVIII which were not included in the graph were given in between dates without corresponding hCG titers; adverse drug reaction to etoposide and cisplatin was noted on EP/EMA XVIII and XIX.

Figure 2

(A) Pulmonary masses (circles) prior to Paclitaxel Carboplatin; (B) Pulmonary masses (circles) after three cycles of Paclitaxel and Carboplatin showing no significant change in size; (C) Cerebellar metastatic focus (green arrows).

Figure 3

(A) hCG regression curve with Paclitaxel Carboplatin; (B) hCG regression curve with Pembrolizumab.

Figure 4

Vaginal mucositis post Pembrolizumab I managed with Prednisone. (A) Rest day 8; (B) Rest day 10; (C) Rest day 11.