Table 3.
Clinical Features of ICPi-AIHA
| Pt | Day of AIHAa | Days since last dose of ICPi | Hgb (g/dL) | LDH peakb (U/L) | Peak retic (%) | Hapto (mg/dL) | Sphero | WBC (x109) | Plt (x109) | DAT | Transfusion requirement | Other IRAEs | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
||||||||||||||
| PT | Nadir | Δ | ||||||||||||
| 1 | 30 | 9 | 12.8 | 8.2 | 4.6 | 885 | 3.3 | UD | Yes | 4.4 | 69c | Neg | pRBCs x4 | ITP |
| 2 | 84 | 42 | 7.2d | 3.5 | 3.7 | 770 | 11.1 | UD | Yes | 4.4 | 279 | IgG (1+), C3 (1+) | pRBCs x4 | None |
| 3 | 119 | 70 | 13.2 | 8.7 | 4.5 | 426 | 8.8 | UD | Yes | 10.6 | 202 | IgG (1+), C3 neg | None | Hepatitis |
| 4 | 265 | 22 | 13.6 | 8.5 | 5.1 | 530 | 4.7 | UD | No | 4.4 | 286 | IgG (2+), C3 neg | None | None |
| 5 | 25 | 25 | 12.4 | 6.2 | 6.2 | 784 | <0.5 | UD | Yese | 4.6 | 344 | Neg | pRBCs x8 | Pyrexia, PRCAf |
| 6 | 13 | 13 | 9.5 | 6.2 | 3.3 | 522g | 3.2 | UD | NA | 3.5 | 71h | NA | pRBCs x2 | None |
| 7 | 377 | 48 | 11.9 | 6 | 5.9 | 505 | 16.8 | UD | Yes | 10.7 | 211 | IgG weak, C3 (2+)i | pRBCs x6 | None |
| 8 | 68 | 5 | 11.7 | 4 | 7.7 | 976 | 14.8 | UD | NA | 38.3 | 127 | IgG3(+), C3 neg | pRBCs x10 | None |
| 9 | 9 | 9 | 9.3 | 7.2 | 2.1 | 791 | 4.9 | UD | Yes | 2.1 | 30 | Neg | pRBCs x2 | ITP |
| 10 | 320 | 21 | 12.9 | 6.4 | 6.5 | 1151 | 6.4 | UD | NA | 13.2 | 347 | IgG weak+, C3 neg; Recurrence: IgG (3+), C3 (1+) | pRBCs x9 | Rash, hypothyroidism |
| 11 | 19 | 19 | 11.7 | 9.4 | 2.3 | 716 | 4.3 | 7 | Yes | 12.3 | 265 | Polyspecific weak | None | None |
| 12 | 42 | 20 | 13.7 | 6.2 | 7.5 | 1574 | 8.5 | UD | No | 16.2 | 200 | Neg | pRBCs x3 | Colitis |
| 13 | 21 | 21 | 10.4 | 6.3 | 4.1 | 399 | 0.3 | 2 | No | 14.5 | 4j | IgG weak+, C3 (2+) | pRBCs x4 | None |
| 14 | 84 | 22 | 10.1 | 5.5 | 4.6 | 623 | 0.3 | UD | Yes | 5.6 | 422k | Neg | pRBCs x4* | ITP; AKI; hepatitis |
| M | 55 | 21 | 11.8 | 6.3 | 4.6 | 743 | 5 | 8.1 | 207 | 4 | ||||
| IQR | 22–110 | 15–24 | 10–13 | 6–8 | 4–6 | 524–862 | 3.3–8.8 | 4.4–13.0 | 85–284 | 2–6 | ||||
Number of days between the first ICPi dose and AIHA onset.
LDH values were normalized to the reference range at Massachusetts General Hospital (110–210 U/L).
BL platelet count 125×109.
BL anemia reported after hemorrhage during recent orthopedic surgery.
Patient had two episodes of AIHA, spherocytes were only reported on the second AIHA episode.
Based on an undetectable reticulocyte count, this patient was suspected of having a concurrent PRCA; however, due to a decline in clinical status, a BMBx was not performed to confirm the diagnosis.
Only one LDH value for this patient.
BL platelet count 70–100 ×109.
Cold agglutinin titer and thermal amplitude negative; 14 of the DATs were positive for C3 (2+) and negative for IgG, and one was weakly positive for IgG and negative for C3.
Patient had a known diagnosis of ITP related to CLL with BL platelet count 4–30×109; platelet count improved to 170 ×109 with glucocorticoids given for ICPi-AIHA.
Within 4 weeks of AIHA, platelet count dropped to 7×109.
Abbreviations: AIHA, autoimmune hemolytic anemia; AKI, acute kidney injury; BMBx, bone marrow biopsy; CLL, chronic lymphocytic leukemia; DAT, direct antiglobulin test; Hapto, haptoglobin; Hgb, hemoglobin; IQR, interquartile range; IRAE, immune related adverse events; ITP, immune thrombocytopenia; LDH, lactate dehydrogenase; M, median; NA, not available; Neg, negative; pembro, pembrolizumab; Plt, platelet count; pRBCs, packed red blood cells; PRCA, pure red cell aplasia; PT, pre-treatment; retic, reticulocyte percentage; RP, retroperitoneal; Sphero, spherocytes; UD, undetectable; WBC, white blood cell count.