ORLANDO-Preliminary results of a French study show improved event-free survival for patients with indolent non-Hodgkin’s lymphoma (NHL) who received high-dose chemotherapy with purged autologous stem cell transplantation as first-line therapy, compared with conventional standard therapy.
ORLANDOPreliminary results of a French study show improved event-free survival for patients with indolent non-Hodgkin’s lymphoma (NHL) who received high-dose chemotherapy with purged autologous stem cell transplantation as first-line therapy, compared with conventional standard therapy.
Eric Deconinck, MD, of Besançon University Hospital, and his associates in the GOELAMS group, reported the preliminary findings of the multicenter randomized phase III study at the 43rd Annual Meeting of the American Society of Hematology (ASH abstract 3573).
At the time of the ASH meeting, the GOELAMS 064 protocol, begun in April 1994, had enrolled 172 patients (age 18 to 60) with newly diagnosed stage II bulky or stage III/IV follicular lymphoma and at least one criteria of high tumor burden. Stage IV NHL was diagnosed in 70% of patients. A total of 144 patients had been analyzed at the time of the ASH presentation, and 124 were evaluable.
Sixty-six patients received standard CHVP (cyclophosphamide, doxorubicin, teniposide, prednisone) chemotherapy plus interferon-alfa-2b (IFN, Intron A) at a dose of 5 × 106 three times a week. They received CHVP monthly for 6 months, then every other month for a total of 12 courses over 18 months.
Fifty-eight patients randomized to high-dose therapy/transplant received three cycles of VCAP (vindesine 3 mg/m² on day 1, cyclophosphamide 1,500 mg/m² on day 2, Adriamycin 80 mg/m² on day 2, and prednisolone 80 mg/m² on days 1 to 5).
The 43 patients in complete or very good partial remission were mobilized after the second or third VCAP cycle with one cycle of IMVP16 (ifosfamide, methotrexate, etoposide). The 15 patients in partial remission or relapse received two cycles of DHAP (dexamethasone, cytarabine, cisplatin) before harvest and stem cell transplant if possible.
Peripheral blood stem cells or bone marrow was harvested followed by B cell purging via negative selection (with immunomagnetic beads) or positive selection (with CD34+ selection).
The overall response rate for patients on the standard chemotherapy arm was 83% vs 90% for the high-dose therapy arm. Although the response rates are comparable in the two groups, the response intensity was better in the high-dose chemotherapy arm: 76% of transplant patients had a complete response or very good partial response vs 46% of standard therapy patients, Dr. Deconinck reported. The investigators saw twice the rate of initial failure to respond in the conventional therapy group (11 vs 5 transplant patients).
At a median follow-up of 31 months, the 4-year event-free survival rate was 61% for the transplant patients vs 37% for the standard therapy patients (P = .018). Overall survival at 4 years, however, did not differ significantly between the two groups (78% for the transplant patients vs 83% for the standard therapy patients). "Longer follow up is needed to determine the impact on overall survival," Dr. Deconinck said.
The purging technique was predictive of relapse: B-cell depletion with immunomagnetic beads resulted in a disease-free survival rate of 33% vs 65% for CD34+ selection, he reported. Dr. Deconinck cautioned that the occurrence of eight cases of secondary cancer (five myelodysplasias) with autologous stem cell transplantation is leading the investigators to reevaluate the benefit of purging in the ongoing trial.