Treatment Response to Single Agent Sphingosomal Vincristine in Patients with Relapsed and/or Refractory Diffuse Aggressive Non-Hodgkin's Lymphoma (NHL): Subgroup Analyses.

Abstract

There is a substantial need for new effective therapies for patients with recurrent or refractory diffuse aggressive NHL. Efficacy and safety of sphingosomal vincristine (SV), a novel formulation of vincristine encapsulated in sphingomyelin liposomes or ‘sphingosomes', were evaluated in a multinational study in aggressive NHL patients with multiple unfavorable prognostic factors. Methods: 119 pts with relapsed or refractory aggressive NHL were enrolled. SV was administered at 2 mg/m2 without capping the dose as a 1 hr IV infusion every 2 weeks. The objective response rate (ORR) and 95% CI for the proportions and difference in proportions were calculated for the following subgroups: by age (≤ 60 vs. > 60); sensitive disease vs. resistant (refractory or relapsed within 3 months of prior treatment); IPI score 0–2 vs. 3–5; prior therapies 2 vs. >2; bone marrow involvement at baseline; and prior ABMT. Results: ORR in the entire group was 25% (7% CR/Cru and 18% PR) (ASH Abstr. 2353, 2003).No of Prior Regimens/Disease SensitivityORR %Sensitive (n=39) Resistant (n=80)41% 18%2 Regimens (n=24)a -Sensitive (n=11) -Resistant (n=13)46% 64% 31%>2 Regimens (n=95) -Sensitive (n=28) -Resistant (n=67)20% 32% 15%aone patient had 1 prior regimenOther Subgroup AnalysesORR %Bone MarrowInvolved (n=20) Not involved (n=93)10% 27%Ageb≥60 (n=60) >60 (n=59)25% 25%IPIb0–2 (n=59) 3–5 (n=58)19% 31%Prior ABMTbYes (n=39) No (n=80)26% 25%bnot statistically significant as 95% CI on the difference in ORR includes zeroConclusion: Single-agent SV was active in heavily pretreated patients with relapsed and/or refractory NHL. A multivariate analysis showed that the two strongest predictors for response were number of prior regimens and sensitivity to the last therapy. The highest level of activity was observed in patients with sensitive disease and 2 prior regimens (ORR 64%). Response to SV in older patients was the same as in younger patients. Prior ABMT did not impact response with ORR being similar in both groups. SV was well tolerated and the safety profile was similar to standard vincristine despite a doubling of dose intensity.