Table 1.

Synopsis of demographics, background, treatment and outcome of described cases.

	Case 1	Case 2
Age and gender	64F	75M
ECOG	0	1 (07/23)
Disease specification	Last disease status (07/2023) Metastatic melanoma with inguinal, iliac and para-aortic lymph node (12/2020) as well as hepatic (09/2022) metastases (pT4b N3c M1a(1) - stage IV AJCC 2017) Disease status at time of AIHA (02/2022 and 09/2022) Metastatic melanoma with inguinal, iliac and para-aortic lymph node (12/2020) metastases (pT4b N3c M1a(1) - stage IV AJCC 2017)	Current disease status (09/2023) Metastatic melanoma with hepatic (ED 12/2022), pulmonary (12/2022) and bone (03/2023) metastases (pT3a cN1c cM1c (1) - stage IV AJCC 2017) Disease status at time of AIHA (09/2022) Metastatic melanoma of the right lower back with a subcutaneous metastasis of the right lower back (06/2021) (pT3a cN1c cM0 - stage IIIB AJCC 2017)
Genomic alterations	BRAF wild type, no evidence of any pathogenic gene sequence variants	BRAF wild type, NRAS: Q61R, ARID1A: Q420H, SF3B1: R549H, PD-L1 positive (5%)
Comorbidities	• Bronchial asthma (since 01/2021)	• Melanoma in situ of the right cheek (03/2019), total excision therapy • Cardiac pacemaker (with a disconnected right ventricular probe since 2003) • Arterial hypertension • Hyperuricemia • Transient ischemic attack in 2019 • Partial bowel resection due to intestinal stenosis in 2005
Melanoma-specific therapy	12/2020 Diagnosis of vulvar melanoma metastasis with para-aortic and pelvic lymph node metastases 01 – 03/2021 4 cycles of immunotherapy with ipilimumab (3mg/kg) and nivolumab (1mg/kg) every three weeks 04 – 11/2021 8 cycles nivolumab flat dose 480 mg every four weeks 12/2021: progression of lymph node metastases 12/2021 – 02/2022 3 cycles of immunotherapy with ipilimumab (3mg/kg) and nivolumab (1mg/kg) every three weeks 02-03/2022 First episode of AIHA (CTCAE grade 3) 04-05/2022 Radiation therapy of inguinal lymph node metastases (cumulative dose of 39 GY) 06-09/2022 3 cycles of immunotherapy with pembrolizumab (200 mg per infusion) every three weeks in combination with Lenvatinib 20 mg per day 09/2022 Second episode of AIHA (CTCAE grade 3) 11/2022 – 12/2022 Radiation therapy of para-aortic lymph node metastasis (cumulative dose of 36 GY) 01-05/2023 5 cycles of chemotherapy with dacarbazine 06-07/2023 Palliative treatment, death in 07/2023	11/2018 Diagnosis of nodular melanoma of the lower right back, excision and sentinel lymph node biopsy (0/1) in 12/2018 05/2022 Resection of a suspected in transit metastasis of the lower right back 08/2022 Radiation therapy in the region of the lower right back (cumulative dose of 50 GY) 08/2022 1 cycle of immunotherapy with pembrolizumab (400 mg per infusion; planned therapy all six weeks) 09/2022 Episode of AIHA (CTCAE grade 3) 03/2023  Radiofrequency ablation of liver metastases, that had been discovered three months earlier 04-05/2023 Pelvic radiation therapy for newly diagnosed iliac bone metastases (cumulative dose of 39 GY)  Since 05/2023  Screening for and inclusion in a clinical trial
Time to AIHA from first dose/from last dose of ICPi	First episode of AIHA: 13 months/2 weeks (ipilimumab/nivolumab) Second episode of AIHA: 2 months/4 weeks (pembrolizumab)	4 weeks
Laboratory/DAT	02/2022 DAT positive, with anti-IgG (128+) and anti-C3d positive antibodies (2+). 03/2022 DAT positive, with anti-IgG (16+) antibodies, negative for anti-C3d antibodies 08/2022 DAT positive, with anti-IgG (8+) and anti-C3d positive antibodies (16+)	09/2022 DAT negative
Treatment of AIHA	First episode of AIHA: Oral Prednisolone (80mg, tapered over weeks) One red blood cell transfusion Second episode of AIHA: Intravenous Prednisolone (70mg, oralized after a few days and tapered over weeks) Two red blood cell transfusions	Intravenous prednisolone (90 mg, oralized after 10 days and tapered over weeks)
Concurrent irAEs	09/2022 Thrombocytopenia (CTCAE grade 1)	Myocarditis (CTCAE grade 2)
Outcome/Time to recovery	First episode: Resolution of AIHA/4 weeks to comparable previous hemoglobin levels Second episode: Resolution of AIHA/6 weeks to comparable previous hemoglobin levels	Resolution of AIHA/26 weeks to comparable previous hemoglobin level