Abstract
Sphingosomal vincristine (SV) is a novel formulation of vincristine encapsulated in sphingomyelin liposomes or ‘sphingosomes’. SV was well tolerated with 45% ORR in multiply relapsed aggressive NHL (
Methods: Patients were treated with standard dose CHOP that included SV 2.0 mg/m2 without dose capping ± rituximab 375 mg/m2, given every 21 days for 6 to 8 courses (
Results: Of 73 patients enrolled in the study, 68 were evaluable for response. Median age was 63 (range 22–80). IPI score was 0–2 in 44 pts and ≥ 3 in 24 pts. Patients received a median of 6 study treatments (range 1–8). ORR was 93% (63/68 pts) with 62 pts achieving CR and Cru (91%), and 1 PR (2%). 3 pts had PD (4%) and 2 were not assessed for response (3%). The median PFS and OS have not been reached at a median follow up of 29.5 months. Responses according to IPI score were as follows:
| Results . | IPI 0–2 (n=44) . | IPI ≥3 (n=24) . | Total (n=68) . |
|---|---|---|---|
| ORR | 93% (41) | 92% (22) | 93% (63) |
| −CR | 77% (34) | 88% (21) | 81% (55) |
| −Cru | 14% (6) | 4% (1) | 10 (7) |
| −PR | 2% (1) | 0% (0) | 2% (1) |
| PD | 5% (2) | 4% (1) | 4% (3) |
| Not Assessed | 2% (1) | 4% (1) | 3% (2) |
| Results . | IPI 0–2 (n=44) . | IPI ≥3 (n=24) . | Total (n=68) . |
|---|---|---|---|
| ORR | 93% (41) | 92% (22) | 93% (63) |
| −CR | 77% (34) | 88% (21) | 81% (55) |
| −Cru | 14% (6) | 4% (1) | 10 (7) |
| −PR | 2% (1) | 0% (0) | 2% (1) |
| PD | 5% (2) | 4% (1) | 4% (3) |
| Not Assessed | 2% (1) | 4% (1) | 3% (2) |
The probability of being progression free at 25 months was 86% (5 relapses and 1 death, reason unknown) for pts with IPI 0–2 and 77% (6 relapses) for pts with IPI ≥3. Overall survival probability was 94% at 28 months (1 death in the group with IPI 0–2 and 2 deaths in the group with IPI ≥3). Neuropathy was generally mild (Gr.1–2). Hematological toxicities were as follows: 64% Gr.3–4 neutropenia, 6% Gr.3 anemia, and 14% Gr.3–4 thrombocytopenia.
Conclusions: CHOP plus rituximab regimen with sphingosomal vincristine substituted for free vincristine demonstrated promising activity with durable responses similar in both groups of patients with IPI score 0–2 and IPI ≥ 3. The treatment was well tolerated with only mild neurotoxicity.
