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Rituximab in Patients with HIV-associated Multicentric Castleman Disease (HIV-MCD). Castlema B-ANRS 117 Trial
Laurence Gérard*1, A Bérezné1, L Galicier1, M Obadia2, N De Castro1, C Jacomet3, R Verdon4, V Meignin1, F Agbalika1, E Oksenhendler1, and CastlemaB-ANRS 117 Study Group
1St Louis Hosp, Paris, France; 2Purpan Hosp, Toulouse, France; 3Hotel Dieu Hosp, Clermont-Ferrand, France; and 4Cote de Nacre Hosp, Caen, France
Backroung: HIV-MCD is a
KSHV/HHV-8 related lymphoproliferative disorder, characterized by a rapidly
progressive and often fatal course and high lymphoma incidence rate. Vinca
alkaloids produce frequent but short-lived responses, and most patients remain
dependant upon chemotherapy. Rituximab, a humanized anti-CD20 monoclonal
antibody, has been reported to be effective in some cases. The present trial
reports the efficacy of rituximab in HIV-infected patients (pts) with MCD.
Methods: Prospective,
multicenter, phase II, open label trial, including patients with confirmed MCD
and dependance upon chemotherapy for at least 3 months. Pts should be on HAART
for at least 3 months, without threshold of CD4 cell count neither HIV-RNA,
with no prior treatment with rituximab, no evolutive lymphoma or Kaposi sarcoma
(KS) requiring specific therapy. Chemotherapy was withdrawn 6 days before the
first of the 4 weekly doses of rituximab (375 mg/m2). Efficacy was assessed by
the complete response (CR) rate at day 60. Pts were followed until day 365 to
assess overall, and disease-free survival, relapse rate, lymphoma-free
survival, and tolerance of rituximab. Data were analysed using an
intent-to-treat analysis.
Results : 24 patients (median
age, 43.7 years ; 21 men) were included between May 03 and Dec 04. At
baseline, median CD4 cell count was 270/mm3, and 18/24 pts had a
plasma HIV-RNA <50 c/ml. All pts received HAART, for a median of 53.5
months. KS (stable or in remission) was associated in 12 pts. Median duration
of MCD was 25 months. MCD treatment at baseline was vinblastine in 4 pts,
etoposide in 18 pts, and adriamycine in 2 pts. Median duration on chemotherapy
was 20.4 months.
Twenty-three pts received the 4
courses of rituximab, and 22 were in CR at day 60. One pt died with MCD (d15)
and 1 pt had a MCD relapse just after the last rituximab infusion (d23). During
rituximab infusions, no severe adverse events were reported.
Relapse was observed
in 3 pts between day 60 and day 365 (5.7, 8.8 and 9.8 months) and one pt died
at 3.7 months, with acute respiratory failure. At day 365, 16 pts were alive in
CR. Two further pts, to date alive in CR, are still ongoing follow-up until Dec
2005. The one-year overall survival and disease-free survival were 92% and
73.5%, respectively. Eight pts experienced mild progression of KS that did not
required specific therapy. No pt developed lymphoma.
Conclusion: Rituximab is an effective therapy in chemodependant
pts with MCD.
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