Trial Information

Targeted Intensification by a New Preparative Regimen for Patients With Low-Grade B-Cell Lymphoma Utilizing Standard-Dose Yttrium-90 Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy (RIT) Combined With High-Dose Beam Followed by Autologous Stem Cell Transplantation (ASCT)

The indolent course of the low-grade B-cell lymphoma is thus characterized by multiple
remissions and relapses with ever-shortening “time to progression” intervals, and by
ultimately becoming refractory to treatment. In this situation of recurrences, intensive
therapy including high-dose chemotherapy or chemo-radiotherapy followed by autologous
hematopoietic stem cell transplantation appears as a therapeutic option. With the use of
peripheral blood stem cell, the autologous stem cell transplantation (ASCT) procedure has
become easier and cheaper, and it has a mortality rate of below 5% and manageable morbidity.
EBMT registry data or institution driven studies have shown an improvement in event free
survival when compared to chemotherapy in relapsing patients. Recently Schouten et al
reported in a randomized study a significant benefit in survival for patients submitted in
relapse to ASCT. Consolidation with ASCT has been studied in first line treatment and showed
a significant improvement in survival in one randomized study. BEAM regimen is a referent
high-dose chemotherapy used in intensive therapy followed by ASCT in the treatment of
malignant lymphoma. It could therefore be considered for patients with indolent lymphoma if
it could be shown to improve survival. In most studies the conditioning regimen was
associating chemotherapy and Total Body Irradiation (TBI) for indolent lymphoma as it is
very sensitive to even low dose of radiotherapy. TBI however is time consuming and
technically not available in all transplant centers and associated with some long term
toxicities; a search for more specific targeted irradiation has been a goal for several
years.

Recently, a new preparative regimen for older patients with aggressive CD20-positive B-cell
lymphoma utilizing standard-dose 0.4 mCi/kg 90Y ibritumomab tiuxetan combined with high-dose
BEAM followed by ASCT showed a CR rate of 92% with a follow-up of 9 months. Finally,
high-dose radioimmunotherapy with 90Y ibritumomab tiuxetan and high-dose
cyclophosphamide/etoposide followed by ASCT for poor-risk or relapsed B-cell NHL have been
reported, with a 2-year DFS of 80%. The use of conventional dose of Yttrium did not need
heavy radioprotection procedures, and can be widely distributed in transplant centers.

Overall toxicities were comparable to standard autologous transplantation conditioning
regimens, and the combined treatment was well tolerated. The hematological reconstitution
after transplantation occurred without delay, except in two cases than in control-based
high-dose chemotherapy alone population. Mucositis and neutropenic fever were reported
without increase of severity. Nonhematological adverse events have been observed, three
interstitial pneumonitis, mild abnormalities on liver or kidney function tests, except one
case of veno-occlusive disease, and 4 fatal infection (disseminated aspergillosis with a
brain abscess, streptococcal sepsis, staphylococcal sepsis, and disseminated varicella
zoster).

Therefore, all these data support a phase II trial evaluating efficacy and toxicities in
patients with low grade B-Cell lymphoma of a new preparative regimen combining a standard
dose 90Y ibritumomab tiuxetan and high-dose BEAM chemotherapy followed by ASCT.