Table 1 Summary of the three available cases of aplastic anemia in the setting of immune checkpoint blockade

Gender/age

M/51

F/48

F/57

Oncologic Dx

Metastatic melanoma

Metastatic melanoma

Metastatic GBM

Baseline CBC

 Hb (g/L)

160

N/A

~ 130

 Plt (× 10⁹/L)

250

N/A

268

 Neut (× 10⁹/L)

2.9

N/A

~ 2.5

ICB agent/dose

Nivolumab (1 mg/kg) + ipilimumab (3 mg/kg) × 2 cycles

Nivolumab (1 mg/kg) + ipilimumab (3 mg/kg) × 4 cycles, N (3 mg/kg) × 5 cycles

Nivolumab (3 mg/kg) × 2 cycles

Presentation of AA

15-days post 2nd cycles of nivolumab + ipilimumab

3-days post 5th cycle of nivolumab

~ 14-days post 2nd cycle of nivolumab

CBC @ AA presentation

 Hb (g/L)

77

115

68

 Plt (× 10⁹/L)

346

< 5

5

 Neut (× 10⁹/L)

0.06

< 0.1

0.00

BM biopsy

< 10% cellularity with trilineage hypoplasia without excess blasts, myelodysplasia, myeloid/lymphoid precursors or a B cell neoplasm. Lymphocyte fraction 84% T cells with an inverted CD4⁺:CD8⁺ ratio (1:2)

~ 10% cellularity, scattered lymphoid and erythroid cells without signs of dysplasia. Absent granulopoiesis and megakaryocytes missing. Majority of lymphoid cells were CD8⁺ T-lymphocytes

Markedly hypocellular marrow with virtual absence of hematopoietic elements. ~ 50% of cells were lymphocutes; majority T-cells. One analyzable metaphase; chromosomally normal

Treatment

Methylprednisone 1 mg/kg q 12 h × 7 days, 1 mg/kg q 24 h × 7 days, packed red blood cells

Prednisone 1 mg/kg/24 h, G-CSF, infection prophylaxis, tranexamic acid, platelet transfusions

Dexamethasone 2 mg PO q 12 h, G-CSF, eltrombopag 50 mg PO q 24 h → 100 mg PO q 24 h, platelet transfusions, packed red blood cells, infection prophylaxis

AA response/outcome

Rapid recovery in neutropenia, gradual recovery in hemoglobin

No response to treatment

No response to treatment

Patient outcome

No current active disease, patient being monitored

Patient mortality at day 11 of hospitalization from intracerebral hemorrhage

Patient mortality 73 days after cycle 2 of Nivolumab