Summary of 4 HCL Patients Treated With LMB-2
| . | Patient No. 15 . | Patient No. 30 . | Patient No. 32 . | Patient No. 35 . |
|---|---|---|---|---|
| Age (yr) | 63 | 47 | 60 | 66 |
| Years with HCL | 13 | 17 | 12 | 13 |
| Previous chemotherapy | IFN, CdA | IFN, CdA | IFN, CdA, DCF | IFN, CdA |
| Spleen | Removed | Enlarged | Removed | Removed |
| Circulating HCL/μL | 63,900 | 478 | 350 | 60,700 |
| CD25/CD11c/CD103 | ++/++/++ | ++/++/++ | ++/++/+ | ++/++/+ |
| CD25 sites/cell | 7,200 | 6,200 | Not done | 1,400-1,900 |
| Dose level of LMB-2 | 30 μg/kg × 3 | 63 μg/kg × 3 | 63 μg/kg × 1 | 40 μg/kg × 3 |
| No. of cycles | 1 | 2 | 1 | 2 |
| Toxicity (grade) | AST/ALT (1) | AST/ALT (1) | Cardiac (4) | Nausea (1) |
| (LMB-2-related) | Fever (2) | Fever (1) | Diarrhea (3) | Weight gain (1) |
| Fever (1) | Rash (1) | |||
| Peak plasma LMB-2 | 219 ng/mL | 593 ng/mL | 1,094 ng/mL | 487 ng/mL |
| Half life | 361 min | 380 min | 260 min | 26 min (α) |
| 984 min (β) | ||||
| LMB-2 neutralized >75% | No | No | No | Yes |
| Response | PR | CR | PR | PR |
| Maximum % reduction in circulating HCL cells | 99.8 | 99.999-100 | 99 | 98 |
| . | Patient No. 15 . | Patient No. 30 . | Patient No. 32 . | Patient No. 35 . |
|---|---|---|---|---|
| Age (yr) | 63 | 47 | 60 | 66 |
| Years with HCL | 13 | 17 | 12 | 13 |
| Previous chemotherapy | IFN, CdA | IFN, CdA | IFN, CdA, DCF | IFN, CdA |
| Spleen | Removed | Enlarged | Removed | Removed |
| Circulating HCL/μL | 63,900 | 478 | 350 | 60,700 |
| CD25/CD11c/CD103 | ++/++/++ | ++/++/++ | ++/++/+ | ++/++/+ |
| CD25 sites/cell | 7,200 | 6,200 | Not done | 1,400-1,900 |
| Dose level of LMB-2 | 30 μg/kg × 3 | 63 μg/kg × 3 | 63 μg/kg × 1 | 40 μg/kg × 3 |
| No. of cycles | 1 | 2 | 1 | 2 |
| Toxicity (grade) | AST/ALT (1) | AST/ALT (1) | Cardiac (4) | Nausea (1) |
| (LMB-2-related) | Fever (2) | Fever (1) | Diarrhea (3) | Weight gain (1) |
| Fever (1) | Rash (1) | |||
| Peak plasma LMB-2 | 219 ng/mL | 593 ng/mL | 1,094 ng/mL | 487 ng/mL |
| Half life | 361 min | 380 min | 260 min | 26 min (α) |
| 984 min (β) | ||||
| LMB-2 neutralized >75% | No | No | No | Yes |
| Response | PR | CR | PR | PR |
| Maximum % reduction in circulating HCL cells | 99.8 | 99.999-100 | 99 | 98 |
Circulating HCL cells in patient no. 32 were too few to perform binding studies. The half lives represent monoexponential decay, except for patient no. 35, for whom 90% of the initial plasma disappearance was rapid and the remaining plasma level decreased more slowly as indicated. The toxicity and pharmacokinetics are shown for the first cycle. Patient no. 30, who received a second cycle had a higher peak LMB-2 level (1,191 ng/mL), with 90% of the plasma level decreasing with a t1/2α of 77 minutes followed by a t1/2β of 420 minutes (see Fig 4B). Toxicity to cycle 2 included non–dose-limiting grade III AST/ALT and grade I fever and grade II nausea, vomiting, and rash.
Abbreviations: ++, strongly positive; +, positive; AST, aspartate transaminase or SGOT; ALT, alanine transaminase or SGPT; PR, partial response; CR, complete remission.