Yt90 Zevalin & Combination Chemotherapy in Treating Patients With Stage II,Stage III,or Stage IV Diffuse Large B-cell Lymphoma
Diffuse large B-cell lymphomas (DLBCL) are the most common lymphoid neoplasm and account for
30% to 40% of adult non-Hodgkin lymphomas (NHL). DLCBL is a potentially curable disease. The
ultimate goals of introducing new modality treatments such as monoclonal antibody
(Ab)-targeted therapy are to increase complete remission (CR) rate and prolong event-free
survival and overall survival.In phase II trials, it was shown that in DLBL the addition of
rituximab to CHOP was feasible, with an increase in ORR, including CR and an increase in the
OS and PFS in patients with DLBL.2 The benefit of R-CHOP was consistent across all subgroups
of patients tested, including good and poor risks according to IPI and independent of
younger than 70 years and older than 70 years of age.
Recently, new radiolabeled monoclonal antibodies have been established in the therapy of
malignant lymphoma which can induce high remission rates. Radiolabeled antibodies are
particularly effective as lymphoma cells are highly sensitive to radiation. In addition, the
local emission of radiolabeled antibodies is able to destroy cells in close proximity to the
bound antibody (bystander effect) therefore circumventing the problem of limited perfusion
of bulky or poorly vascularized tumors.Ibritumomab is covalently linked to the tiuxetan
chelate and radiolabeled with Yt90, producing Yt90-ibritumomab tiuxetan (Yt90-Zevalin). To
optimize biodistribution, Rituximab is given prior to the radiolabeled antibody.
Yt90-ibritumomab-tiuxetan-treatment was compared to a standard course of Rituximab. ORR in
the Yt90-ibritumomab tiuxetan group was significantly higher than ORR in the Rituximab group
(80% vs. 56% according to International Workshop Response criteria or 73% vs. 47% according
to protocol-defined evaluation of response).
Since radioimmunotherapy represents a significant advance over unlabeled immunotherapy for
the treatment of patients with B-cell non-Hodgkin's lymphoma, it is worthwhile to study the
consolidation therapy with Yt90-ibritumomab tiuxetan (Yt90-Zevalin) in patients who achieved
at least unconfirmed partial remission after 6 cycles of CHOP therapy.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
- Determine the 2-years progression-free survival of consolidation therapy with Yt90-Zevalin.
Surapol Issaragrisil, M.D.
Thailand: Food and Drug Administration