Background and Importance Immune checkpoint inhibition (ICI) can induce responses in patients with advanced malignancies. Although a well-established downside of ICI is its diverse spectrum of immune-related adverse events, the incidence of second primary malignancies associated with ICI is still a matter of debate.
Aim and Objectives We present two consecutive patients treated in our Hospital in 2022 who developed clinically acute myeloid leukaemia (AML) during or after ICI treatment for solid tumours.
Patient 1 is a man with a previous history of metastatic lung adenocarcinoma treated with pembrolizumab, which was stopped due to complete response (CR) 5 months before diagnosis of AML in April 2022. Patient 2 is a woman, with a previous history of ductal breast cancer treated with adjuvant chemoradiotherapy; she also developed a metastatic V600E BRAF-mutated melanoma, treated with BRAF/MEK inhibitors. Finally after two months of pembrolizumab, she developed AML in April 2022.
Material and Methods In both Patients 1 and 2, peripheral blood (PB) and bone marrow blood testing confirmed Core Binding Factor (CBF) AML, according to the presence of (inv16) (p13;q22) in 80% and 70% of blasts in the PB, respectively.
According to ESMO AML Guidelines, therapy with gemtuzumab ozogamycin associated standard chemotherapy was recommended for both patients.
Results Patient 1 achieved a CR after induction and consolidation therapy; patient 2 performed cytarabine-based consolidation therapy due to leukaemia-aberrant immunophenotype. Both patients are alive at current follow-up (4 months after diagnosis).
Conclusion and Relevance A case of AML after 3 cycles of pembrolizumab for the treatment of non-small-cell lung cancer and 5 cases of myeloid neoplasia after treatment with ICIs were recently reported.
Hyperprogression of subclinical myeloid malignancies could be a potential explanation since a myeloid clone with acquired driver mutation(s) could obtain an extra proliferation advantage from functional myeloid PD-1 knockout after ICI. Abberant PD-1 expression was observed in 8–26% of CD34+ blasts in myelodysplastic syndromes, chronic myelomonocytic leukaemia, and AML. Moreover chemotherapy and BRAF inhibitor exposure, together with short exposure to pembrolizumab in Patient 2, suggest a major role of previous therapies in the development of AML.
The correlation between ICI and myeloid neoplasias is still uncertain.
Van Eijs MJM, et al. Cancer Immunol Immunother (2022).
Conflict of Interest No conflict of interest
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