From July 1994 until March 1998, 131 patients with follicular lymphoma, all grades, were randomized between 12 courses of CHVP (cyclophophamide, doxorubicin, VP-26, and prednisone) + 18 months of interferon-alfa-2b (Intron A), 5 MU three times weekly (arm A; 70 patients) or fludarabine (Fludara), 12 courses of 5 days in 18 months (arm B; 61 patients). All patients were older than 60 years and had a high tumor burden, defined as at least one of the following parameters: poor performance status, high lactic dehydrogenase (LDH) or beta-2-microglobulin levels, lymph node tumor > 7 cm, serous localization, huge splenomegaly, or compressive syndrome.
All analyses were done on an intent-to-treat basis, with 11 patients having a nonfollicular indolent lymphoma after centralized review. Twelve percent of patients had follicular large cell lymphoma; 66%, bone marrow infiltration; 66%, a tumor mass > 7 cm; 13%, a performance status > 1; 28%, B-symptoms; 43%, high LDH; 61%, high beta-2-microglobulin levels; and 77%, more than one criterion of adverse prognosis. No statistical difference existed between the two arms with respect to clinical or biological parameters, as well as parameters defining aggressive disease.
Three patients died during treatment, two in arm A and one in arm B. More toxic events were observed in arm A: 26% of courses with grade 3-4 neutropenia, compared to 5% in arm B, with < 1% of courses with grade 3-4 infection in both arms. In arm A, 22 patients stopped interferon and 8 had a dose reduction because of adverse events (43% of the patients).
After 6 months, 71% and 59% of patients in arms A and B, respectively, responded, and 21% and 39% progressed (P = .005). At 18 months, 19 patients were not analyzable for response (treatment not yet finished), 57% and 39% of patients in arms A and B, respectively, reached a complete response (CR)/partial response (PR), and 36% and 52% progressed (not significant). With a median follow-up of 25 months, time to progression and survival were significantly shorter in arm B (P = .02 and P = .04, respectively) with a 2-year survival of 81% vs 59% in arms A and B, respectively.
In a multiparametric analysis, only the number of adverse criteria and the treatment were statistically associated with survival. Results were identical if only follicular lymphoma patients were analyzed.
CONCLUSION: These results confirmed the good outcome of patients treated with CHVP + interferon and showed that this combination is associated with a longer survival than fludarabine alone in elderly patients with high-risk follicular lymphoma.