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
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.