TABLE 1.
Main Characteristics of 79 PML Patients at ICI Initiation
| Characteristic | All, n = 79 | Hematological Malignancies, n = 38 a | Primary Immunodeficiencies, n = 14 b | HIV/AIDS, n = 12 | Chronic Inflammatory Diseases, n = 8 c | Solid Neoplasm, n = 5 d | Transplant Recipients, n = 2 e |
|---|---|---|---|---|---|---|---|
| Male sex, n (%) | 52 (65.8) | 24 (63.1) | 10 (71.4) | 8 (66.7) | 4 (50) | 5 (100) | 1 (50) |
| Age at PML diagnosis, yr, median (IQ25–75) | 62.0 (51.0–71.5) | 69.5 (61.8–75.8) | 50.0 (42.8–59.5) | 47.5 (35.5–51.5) | 61.0 (57.5–71.25) | 70.0 (66.0–71.0) | 74.0 (70.5–77.5.) |
| Time from symptom onset to PML diagnosis, days, median (IQ25–75) |
39 (19.0–73.5) [78/79] |
45 (19.0–68.0) [37/38] |
47.5 (33.3–77.8) | 37 (11.5–134.3) | 33.5 (27.5–67.3) | 19 (14–53) | 21.5 (16.3–26.8) |
| Time from PML diagnosis to ICI initiation, days, median (IQ25–75) | 22.5 (10.3–39.5) [78/79] | 19 (6–35) [37/38] | 26 (19.8–61.0) | 27.5 (20.8–36.5) | 31.5 (12.3–49.0) | 22 (19–43) | 8.5 (7.3–9.8) |
| mRS, median (IQ25–75) | 3 (2–4) [76/79] | 3 (3–4) [36/38] | 3 (3–4) | 3 (2–4) | 4 (3–4) [7/8] | 3 (2–4) | 5 (5–5) |
| Brain lobes affected, n, median (IQ25–75) | 3 (2–4) | 3 (2–5) | 3 (2–3) | 4 (3–5) | 3 (2–3) | 3 (2–4) | 3 (3–4) |
| Patients with PML contrast‐enhancing lesions, n (%) | 21 (26.6) | 10 (26.3) | 2 (14.3) | 3 (25) | 4 (50) | 2 (40) | 0 (0) |
| Blood lymphocyte count per μl, median (IQ25–75) | 860 (555–1,286.5) [70/79] | 850 (560–1,335.5) [31/38] | 790 (580–879) | 1,308.5 (1,228.3–2,015) | 675 (490–950) [6/8] | 870 (530–1,270) | 331.5 (253.8–409.3) |
| Blood CD4+ T‐cell count per μl, median (IQ25–75) | 185 (107.5–354.5) [70/79] | 196 (109–418.5) [31/38] | 205.5 (102.3–346.3) | 119 (84.3–249) | 203 (158.3–277.8) [6/8] | 154 (140–217) | 181.5 (128.8–234.3) |
| Blood CD8+ T‐cell count per μl, median (IQ25–75) | 273.5 (84.5–584.8) [68/79] | 235 (91.3–373.8) [30/38] | 184.5 (75–497.3) | 853.5 (616–1,036.3) | 203.5 (77.5–330.3) [6/8] | 164.5 (105.3–257.5) [4/5] | 63 (61–65) |
| JCV DNA level in CSF, log copies/ml, median (IQ25–75) f | 3.8 (2.7–4.9) [60/79] | 4.16 (2.7–5.3) [26/38] | 3.7 (2.8–4.5) [12/14] | 4.0 (2.8–4.4) [11/12] | 4.4 (3.2–5.4) [6/8] | 2.8 (2.4–3.5) [4/5] | 2.9 (2.9–2.9) [1/2] |
| Immunosuppressive treatment before PML diagnosis, n (%) g | 47 (59.5) | 36 (94.7) | 2 (14.3) | 1 (8.3) h | 6 (75) | 0 (0) | 2 (100) |
All baseline variables refer to data at or closest to the time of ICI initiation, unless specified.
In cases of missing data, the actual number of patients is indicated in brackets after each result.
B‐cell non‐Hodgkin lymphoma (23/38, 60.5%), chronic lymphoid leukemia (8/38, 21.1%), Hodgkin lymphoma (3/38, 7.9%), T‐cell lymphoma (2/38, 5.3%), myeloma (1/38), and acute myeloid leukemia (1/38).
Primary immunodeficiencies included idiopathic common variable immunodeficiency (n = 11, 1 defect in DOCK8, 1 defect in CD40 ligand, others without an identified genetic defect), idiopathic CD4 T‐cell lymphocytopenia (n = 2), idiopathic CD8 T‐cell lymphocytopenia (n = 1).
Multiple sclerosis (n = 2), sarcoidosis (n = 1), rheumatoid arthritis (n = 1), myasthenia gravis (n = 1), Erdheim–Chester disease (n = 1), systemic lupus erythematosus (n = 1), overlap syndrome (n = 1). Seven received immunosuppressive drugs; the patient with Erdheim–Chester disease received interferon‐alpha.
Lung cancer (n = 2), prostate cancer (n = 1), cholangiocarcinoma (n = 1), hepatocellular carcinoma (n = 1). None had chemotherapy before PML onset, but 1 had radiotherapy for prostate cancer, and 1 had hepatic embolization for cholangiocarcinoma.
Kidney transplant (n = 2).
Among the 71 patients with CSF JCV DNA positivity at diagnosis, 11 patients (15.5%) had qualitative results only.
Immunosuppressive medications were represented by chemotherapy with or without rituximab or ibrutinib for 35/47 patients (74.5%, including 1 allogeneic hematopoietic stem cell transplantation), rituximab only for 5 patients (10.7%), fingolimod only for 1 patient (1.8%), steroids, methotrexate, or leflunomide for 3 patients (10.6%), and antirejection therapies for 2 patients (4.3%).
This HIV/AIDS patient received etoposide and rituximab for a multicentric Castleman disease.
Abbreviation: AIDS = acquired immunodeficiency syndrome; CSF = cerebrospinal fluid; HIV = human immunodeficiency virus; ICI = immune checkpoint inhibitor; IQ25–75 = interquartile range; JCV = JC polyomavirus; mRS = modified Rankin Scale; PML = progressive multifocal leukoencephalopathy.