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BioOncology Watch Timely Information for Practicing
Physicians |
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FEBRUARY 2002 Non-Hodgkin's Lymphoma (NHL) CHOP plus rituximab vs. CHOP
alone. In Phase II
studies rituximab in combination with CHOP chemotherapy was well tolerated
and induced responses in >90% of patients with indolent or aggressive
lymphoma. As a result, a multicenter,
randomized trial to compare CHOP (cyclophosphamide 750 mg/m2 on
day 1, doxorubicin 50 mg/m2 on day 1, vincristine 1.4 mg/m2,
and prednisone 40 mg/m2 for 5 days every 3 weeks) plus rituximab
(375 mg/m2 on day 1 of each cycle) to CHOP alone (8 cycles) in
elderly (60 to 80 years old) previously untreated patients with diffuse large
B-cell lymphoma was conducted by the Groupe d'Etude des Lymphomes de l'Adulte
(GELA) in France, Belgium, and Switzerland (N=399). The complete response (CR) rate was greater in the CHOP plus
rituximab group (76% vs 63%; p=0.005).
Event-free survival was longer in patients treated with CHOP plus
rituximab (p<0.001) and the 2-year survival rate was 70% compared to 57%
for those treated with CHOP alone (p=0.007).
Adverse experiences were similar in the two treatment groups. These data indicate that the addition of
rituximab to CHOP increases the CR rate and prolongs survival in elderly
patients with diffuse large B-cell lymphoma.
An accompanying editorial by Bruce Cheson concluded that these results
are exciting but cautioned that they need to be confirmed (a large US trial
of CHOP vs CHOP plus rituximab has recently been completed and is undergoing
analysis) and that longer follow-up is required to show that the advantage
conferred by rituximab persists.
(Coiffer B, et al. N Engl J Med 2002; 346:235-242 and Cheson B.
N Engl J Med 2002;346:280-282) B-Cell Chronic Lymphocytic Leukemia (CLL) CD20 levels and response to
rituximab.
Complement-dependent cytotoxicity is thought to be an important
mechanism of action for rituximab.
Josee Golay and colleagues showed that the level of CD20 expressed in
cells isolated from patients with B-CLL, prolymphocytic leukemia, and mantle
cell lymphoma (as measured by immunofluorescence or calibrated beads)
correlated linearly with lytic response to rituximab and complement in
vitro. Although CD55 and CD59
levels did not predict susceptibility to complement, blocking both CD55 and
CD59 increased lysis 5- to 6-fold in B-CLL samples responding poorly to
rituximab. Thus, these data show that
CD20, CD55, and CD59 are important determinants of response to rituximab and
complement in vitro. Other
factors may be important as previous investigations (Weng W-K and Levy R. Blood
2001;98:1352-1357) have not found the expression of CD55 and CD59 or in
vitro susceptibility to complement-mediated lysis to predict clinical
outcome to rituximab. (Golay J, et al. Blood 2001;98:3383-3389) Neuroblastoma
(NB) Anti-GD2 monoclonal
antibody therapy. The
activation of complement by 3F8 (a murine IgG monoclonal antibody directed
against the ganglioside GD2) may mediate the destruction of
neuroblasts observed in vitro.
Brian Kushner and coworkers conducted a phase II study in NB patients
who were incomplete responders to intensive chemotherapy and were treated
with 3F8 (10 mg/m2/day intravenous infusion on days 6-10 and
13-17) combined with subcutaneous granulocyte-macrophage colony-stimulating
factor (GM-CSF). Twelve (80%) of 15 patients with bone marrow refractory
disease achieved a CR and 3 other patients had prolonged progression-free
survival (12 to 21+ months). Five of
10 patients with recurrent NB had CRs in bone marrow. However, 15 patients with bulky
progressive disease continued to progress through 3F8/GM-CSF treatments
(although 2 patients did have scintographic findings suggestive of a
transient response). These preliminary findings suggest that 3F8/GM-CSF treatments
are potentially effective therapy for minimal residual NB in bone marrow.
(Kushner BH, et al. J Clin Oncol 2001;19:4189-4194) Chronic
Myelogenous Leukemia (CML) Effect of pretransplant
interferon (IFN) therapy. The
impact of prior IFN therapy on allogeneic transplantation outcome is
unclear. In a previous study limited
to recipients of unrelated bone marrow, IFN was found to have an adverse
effect on survival if it had been given for >6 months before transplantation
(Morton AJ, et al. Blood 1998;92:394-401). Stephanie Lee and associates reviewed data on 740 patients who
had received unrelated donor transplants for CML in first chronic phase
provided by the International Bone Marrow Transplant Registry and the
National Marrow Donor Program. Prior
IFN had been administered to 489 (66%) patients while 251 (34%) patients had
not been exposed to IFN. Disease
characteristics for the two groups were similar at diagnosis. No effect of IFN exposure was detected for
overall survival, leukemia-free survival, nonrelapse mortality, engraftment,
relapse, or acute/chronic graft-versus-host disease. Thus, this retrospective review failed to
uncover an adverse effect of prior IFN therapy on the outcome of unrelated
donor transplantation. (Lee SJ, et
al. Blood 2001;98:3205-3211) Transplantation
Nonablative allogeneic
hematopoietic transplantation. Issa Khouri et al performed a pilot study of combination
therapy with fludarabine and cyclophosphamide given at conventional
non-myeloablative doses in 20 consecutive patients with recurrent follicular
or small-cell lymphocytic lymphoma (9 patients also received rituximab). Twelve patients were in CR by the time of
transplantation and all patients achieved engraftment of donor cells. All patients achieved a CR and none have
relapsed after a median follow-up of 21 months. These early findings suggest that nonablative chemotherapy with
fludarabine and cyclophosphamide followed by allogeneic stem cell transplantation
is a promising therapy for patients with indolent lymphoma and further study
is warranted. (Khouri IF, et al. Blood
2001;98:3595-3599) |
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