Patient and disease characteristics
| Characteristic . | N = 49 . |
|---|---|
| Age (year) | |
| Median (IQR) | 61.0 (55.0-67.0) |
| Range | 40.0-73.0 |
| Sex | |
| Female | 16 (33%) |
| Male | 33 (67%) |
| ECOG score | |
| 0 | 24 (49%) |
| 1 | 25 (51%) |
| Prior history of or current Richter transformation | 9 (18%) |
| Prior history of Richter transformation | 7 (14%) |
| Current Richter transformation | 2 (4%) |
| No. of prior therapies | |
| Median (IQR) | 5.0 (4.0-7.0) |
| Range | 1.0-10.0 |
| Prior fludarabine | 14 (29%) |
| Prior bendamustine | 25 (51%) |
| Prior venetoclax | 19 (39%) |
| High-risk cytogenetics∗ | 46 (94%) |
| Complex karyotype† (n = 48) | 36 (75%) |
| 17p deletion | 33 (67%) |
| Intolerance to and/or progression on ibrutinib | 47 (96%) |
| Intolerance to ibrutinib | 5 (10%) |
| Progression on ibrutinib | 43 (88%) |
| Prior allogeneic HCT | 7 (14%) |
| Bridging chemotherapy | 8 (16%) |
| Absolute lymphocyte count (109/L) | |
| Median (IQR) | 1.8 (1.0-7.1) |
| Range | 0.2-58.9 |
| Absolute CD4+T-cell count (cells per μL) | |
| Median (IQR) | 547.3 (238.2-937.0) |
| Range | 59.8-4408.7 |
| Absolute CD8+T-cell count (cells per μL) | |
| Median (IQR) | 350.4 (197.8-735.1) |
| Range | 12.4-9403.2 |
| Percentage of CLL cell count in the blood by MFC (% of WBCs; n = 47) | |
| Median (IQR) | 22.3 (4.0-60.0) |
| Range | 0.0-92.0 |
| Marrow CLL burden | |
| Percentage of CLL cells in the BM by IHC (%) (n = 43) | |
| Median (IQR) | 60.0 (12.5-70.0) |
| Range | 0.0-90.0 |
| Percentage of CLL cells in BM by MFC (%) | |
| Median (IQR) | 49.4 (14.1-73.5) |
| Range | 0.0-96.0 |
| Serum LDH concentration (U/L) | |
| Median (IQR) | 200.0 (153.0-308.0) |
| Range | 94.0-1872.0 |
| Tumor cross-sectional area‡ (mm2) | |
| Median (IQR) | 3092.9 (1489.7-4436.4) |
| Range | 0.1-20 406.2 |
| Maximum SUV (n = 37) | |
| Median (IQR) | 5.1 (3.7-7.5) |
| Range | 0.0-27.5 |
| Bulky disease§ | 13 (27%) |
| LD regimen | |
| Concurrent Cy/Flu‖ | 27 (55%) |
| Sequential Cy/Flu¶ | 19 (39%) |
| Cy only (2 g/m2 × 1 day) | 1 (2%) |
| Flu only (25 mg/m2 × 3 days) | 2 (4%) |
| CAR T-cell dose level | |
| 2 × 105 cells per kg | 5 (10%) |
| 2 × 106 cells per kg (recommended phase 2 dose)# | 43 (88%) |
| 2 × 107 cells per kg | 1 (2%) |
| Characteristic . | N = 49 . |
|---|---|
| Age (year) | |
| Median (IQR) | 61.0 (55.0-67.0) |
| Range | 40.0-73.0 |
| Sex | |
| Female | 16 (33%) |
| Male | 33 (67%) |
| ECOG score | |
| 0 | 24 (49%) |
| 1 | 25 (51%) |
| Prior history of or current Richter transformation | 9 (18%) |
| Prior history of Richter transformation | 7 (14%) |
| Current Richter transformation | 2 (4%) |
| No. of prior therapies | |
| Median (IQR) | 5.0 (4.0-7.0) |
| Range | 1.0-10.0 |
| Prior fludarabine | 14 (29%) |
| Prior bendamustine | 25 (51%) |
| Prior venetoclax | 19 (39%) |
| High-risk cytogenetics∗ | 46 (94%) |
| Complex karyotype† (n = 48) | 36 (75%) |
| 17p deletion | 33 (67%) |
| Intolerance to and/or progression on ibrutinib | 47 (96%) |
| Intolerance to ibrutinib | 5 (10%) |
| Progression on ibrutinib | 43 (88%) |
| Prior allogeneic HCT | 7 (14%) |
| Bridging chemotherapy | 8 (16%) |
| Absolute lymphocyte count (109/L) | |
| Median (IQR) | 1.8 (1.0-7.1) |
| Range | 0.2-58.9 |
| Absolute CD4+T-cell count (cells per μL) | |
| Median (IQR) | 547.3 (238.2-937.0) |
| Range | 59.8-4408.7 |
| Absolute CD8+T-cell count (cells per μL) | |
| Median (IQR) | 350.4 (197.8-735.1) |
| Range | 12.4-9403.2 |
| Percentage of CLL cell count in the blood by MFC (% of WBCs; n = 47) | |
| Median (IQR) | 22.3 (4.0-60.0) |
| Range | 0.0-92.0 |
| Marrow CLL burden | |
| Percentage of CLL cells in the BM by IHC (%) (n = 43) | |
| Median (IQR) | 60.0 (12.5-70.0) |
| Range | 0.0-90.0 |
| Percentage of CLL cells in BM by MFC (%) | |
| Median (IQR) | 49.4 (14.1-73.5) |
| Range | 0.0-96.0 |
| Serum LDH concentration (U/L) | |
| Median (IQR) | 200.0 (153.0-308.0) |
| Range | 94.0-1872.0 |
| Tumor cross-sectional area‡ (mm2) | |
| Median (IQR) | 3092.9 (1489.7-4436.4) |
| Range | 0.1-20 406.2 |
| Maximum SUV (n = 37) | |
| Median (IQR) | 5.1 (3.7-7.5) |
| Range | 0.0-27.5 |
| Bulky disease§ | 13 (27%) |
| LD regimen | |
| Concurrent Cy/Flu‖ | 27 (55%) |
| Sequential Cy/Flu¶ | 19 (39%) |
| Cy only (2 g/m2 × 1 day) | 1 (2%) |
| Flu only (25 mg/m2 × 3 days) | 2 (4%) |
| CAR T-cell dose level | |
| 2 × 105 cells per kg | 5 (10%) |
| 2 × 106 cells per kg (recommended phase 2 dose)# | 43 (88%) |
| 2 × 107 cells per kg | 1 (2%) |
Unless otherwise noted, data are n (%).
All variables were assessed before LD chemotherapy, unless specified.
ECOG, Eastern Cooperative Oncology Group; IHC, immunohistochemistry; LDH, lactate dehydrogenase; WBC, white blood cell.
Defined as 17p deletion and/or complex karyotype.
Defined as ≥3 chromosomal abnormalities.
For patients with evaluable nodal disease (n = 45); the sum of the product of the diameters of up to 6 of the largest lymph nodes or masses evaluated on the pre-LD CT.
Defined as largest lymph node ≥5 cm.
Cy 300 to 500 mg/m2 × 3 days + Flu 20 to 30 mg/m2 × 3 days.
Cy 30 to 60 mg/kg or 1 g/m2 × 1 day, then Flu 25 mg/m2 × 3 or 5 days.
One patient with Richter transformation was treated on a dose-dense protocol, in which a second infusion of CAR T cells was administered on day +14 without interval LD.