Yttrium-90 ibritumomab tiuxetan (Zevalin) followed by BEAM (Z-BEAM) conditioning regimen and autologous stem cell transplantation (ASCT) in relapsed or refractory high-risk B-cell non-Hodgkin lymphoma (NHL): a single institution Italian experience

Abstract

Chemo-refractory NHL has a very poor outcome; the addiction of RIT to salvage regiment pre ASCT had recently demonstrated promising results.We performed a retrospective sequential study to determine the feasibility of standard Zevalin with BEAM in high-risk relapse/refractory NHL. A matched cohort analysis with a group treated with standard BEAM without Zevalin was performed as secondary endpoint. Between October 2006 and January 2013, 37 NHL patients at high risk for progression or early (< 1 year) or multiple relapses were treated with Z-BEAM and ASCT after R-DHAP or R-ICE as salvage therapy. Clinical characteristics were 19 refractory and 18 early or multiple relapse; 16 patients received 1, and 21 had 2 or more previous rituximab-containing chemotherapy. At the end of treatment, response was CR 22 (59%), PR 10 (27%), PD 4 (11%), and toxic death (TD) 1 (3%). With a median follow up of 61 months, 3-year PFS was 61% and OS 61%. Fifteen patients died, 12 of lymphoma. Comparison with 21 treated with BEAM alone showed a numerical higher 3-yr PFS rate in favor of Z-BEAM but not statistically significant (57 vs 48%). With the limitation of the small sample subgroup analysis, a significant benefit was observed in relapsed patients for PFS (78% Z-BEAM vs 22% BEAM p = 0.016) and OS (83% Z-BEAM vs 22% BEAM p = 0.001). In relapsed/refractory high-risk NHL, Z-BEAM+ASCT is able to achieve a good ORR. Three-year PFS is promising for early relapsed patients but is not satisfactory for those with refractory disease.

Antibody Therapies for Large B-Cell Lymphoma

“…Despite the safe toxicity profile of Z-BEAM, the primary endpoint (12-year PFS) was not met, though a trend of better OS using BEAM was observed. 33 Similarly, a nonsignificant trend of better PFS with the Z-BEAM–conditioning regimen compared with BEAM alone in R/R DLBCL transplantcandidates has been reported by a single-center retrospective analysis. 34 Due to a lack of clear evidence of effectiveness on DLBCL, interest in further investigations and clinical use of Zevalin for this disease is relatively sparse nowadays.…”

A Systematic Review of Clinical Applications of Anti-CD20 Radioimmunotherapy for Lymphoma

“…A numerically, but nonstatistically significant, higher 3-year PFS was observed for those receiving 90Y-IT, compared to the control group. 31 An earlier study comparing BEAM with iodine-131 tositumomab/BEAM with ASCT for chemotherapy-sensitive relapsed DLBCL produced similar 2-year PFS and OS rates. 32 …”

“…Ciochetto conducted a retrospective analysis of patients with aggressive NHL, R/R to rituximab-containing chemotherapy, who received 90Y-IT followed by the high-dose conditioning regimen BEAM (carmustine, etoposide, citarabine, and melphalan) and ASCT or matched controls who received only BEAM before ASCT. 31 The 90Y-IT group had a CR and PR of 59% and 27%, respectively, and at 61 months, the 3-year PFS and OS were both 61%. Within the study period, 15 died, 12 of lymphoma.…”

Anti-CD25 radioimmunotherapy with BEAM autologous hematopoietic cell transplantation conditioning in Hodgkin lymphoma

“…21,22 Radioimmunotherapy (RIT) is a targeted approach for delivery of RT that has been shown to be safe and effective as a treatment for non-Hodgkin lymphoma (NHL) and has been incorporated into AHCT conditioning regimens. [23][24][25][26][27][28][29][30][31][32][33][34] CD25 is the interleukin-2 receptor α-subunit (IL-2αR) and is expressed on Reed-Sternberg (RS) cells and lymphocytes in the surrounding tumor microenvironment in HL. There have been several RIT trials evaluating radio-labeled antibodies directed against CD25 in patients with lymphoma, including HL, which have demonstrated tolerability and anti-tumor activity.…”