Phase II Study of Sphingosomal Vincristine in CHOP+/ − Rituximab for Patients with Aggressive Non-Hodgkin’s Lymphoma (NHL): Promising 3 Year Follow-Up Results in Elderly Patients.

Background: Individuals older than 60 years have a worse prognosis than younger patients with aggressive NHL. Vincristine is an active drug in the treatment of malignant lymphomas. Sphingosomal vincristine (SV) was well tolerated with 45% ORR in patients with multiple relapses of aggressive NHL (ASH abst. 412, 1999). Based on these data, a phase II study of CHOP with rituximab (no rituximab for T-cell histology), and substituting SV for free vincristine, was undertaken in patients with previously untreated aggressive NHL.

Methods: Aggressive NHL histologies eligible for study were diffuse large B-cell lymphoma (DLCL), peripheral T-cell lymphoma (PTCL), follicular lymphoma grade 3 (FL gr3), anaplastic large cell lymphoma (ALCL), and indolent lymphomas with aggressive transformation (TL). 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 on study, 68 were evaluable for response. Median age was 61 (range 22–80), 36 patients (53%) were >60 years old. Overall, 24 patients (23 elderly) had an IPI score ≥3. Patients received a median of 6 study treatments (range 1–8). Diagnoses were: DLCL = 56; FL gr 3 = 4; PTCL = 4; ALCL = 2 and TL = 2. ORR was 92.6% (63/68 pts) with 55 pts achieving CR (80.1%), 7 CRu (10.3%), and 1 PR (1.5%); 3 patients had PD (4.4%) and 2 were not assessed for response (2.9%). ORR was similar in both elderly (>60) and younger pts (≤60): 91.9% and 93.5% respectively. Neuropathy was generally mild (Gr.1–2). Hematological toxicities were as follows: 56% Gr.3–4 neutropenia, 6% Gr.3 anemia, and 13% Gr.3–4 thrombocytopenia. Toxicites were comparable in elderly and younger patients. The median follow up for the study is 39.6 months (mos), and overall survival 94%. There have been 9 relapses (5 DLCL, 3 T-cell, 1 FL gr3, 1 transformed) for elderly patients and 5 relapses (4 DLCL, 1 T-cell) for patients ≤60. The table below shows progression free survival (PFS) at 3 years, for all histologies, and DLCL by age. There is no difference between the age groups.

Conclusions: This regimen, with sphingosomal vincristine in CHOP +/− Rituximab, has a high overall response rate. It is a well-tolerated therapy with mild neurotoxicity for all patients. At 3 years, the PFS in elderly patients with DLCL treated with RCHOP is comparable to that of younger patients, despite a larger fraction of high risk IPI in the older patients. This regimen merits randomized comparison to RCHOP in DLCL.