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 (

ASH Abst. 412, 1999
). The addition of rituximab to CHOP improves response in aggressive B-cell lymphomas in the elderly (
Coiffier et al., NEJM 2002:346; 235–42
). Based on these data, a phase II study of RCHOP, substituting SV for free vincristine, was undertaken in patients with previously untreated aggressive NHL (excluding rituximab if T-cell lymphoma).

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 (

ASH Abst. 338, 2002
).

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:

ResultsIPI 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) 
ResultsIPI 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.

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