90-Yttrium Ibritumomab Tiuxetan (Zevalin) and BEAM Chemotherapy (Z-BEAM) Vs BEAM for Autologous Stem Cell Transplantation in Lymphoma: Toxicity and Long Term Outcome From a Retrospective Multicentric Study of 123 Patients.

There is a need for improving conditioning regimens in poor risk Non Hodgkin Lymphoma (NHL) patients (pts) eligible for autologous stem cell transplantation (ASCT). Incorporating radioimmunotherapy in the conditioning is an option. Bexxar-BEAM does not appear to be superior to BEAM in relapsed Diffuse Large B –cell lymphoma (DLBCL). The benefic risk ratio of 90-yttrium ibritumomab tiuxetan (Zevalin) BEAM remains to be established.

We analyzed retrospectively the efficacy and the toxicity of Zevalin combined with BEAM chemotherapy (Z-BEAM) compared with BEAM alone followed by ASCT. From January 2000 to November 2004 (BEAM group) and from June 2005 to December 2011 (Z-BEAM group), 55 and 68 pts respectively were treated in 6 French centers (male n=78, female n=45). Zevalin was administered on day-14 prior to ASCT with standard dose of 0.4 mci/kg (n=32) or 0.3 mci/kg (n=36) chosen according to bone marrow reserve. The efficacy and toxicity were compared between the two groups.

The study included 123 pts (median age: 53 years old; range 21–69) with different histological subtypes (58 DLBCL, 19 Mantle cell lymphomas, 37 follicular lymphoma, 3 marginal zone lymphoma, 4 MALT lymphoma and 2 B-lymphocytic lymphoma). Fifty-four pts were treated in first line (20 in the Z-BEAM group and 34 in the BEAM group) and 69 pts in second line (Z-BEAM, n=48; BEAM, n=21). The median time to platelets engraftment (>20000/mm3) was 9 days and 10 days in the Z-BEAM and BEAM group respectively (p=0.334), and the median time to neutrophil engraftment (>500/mm³) was 11 days and 12 days respectively (P=0.117). Grade 3/4 infectious events were more frequent in the Z-BEAM group (80.9%) than in the BEAM group (56.4%), p=0.0001. Grade 3/4 mucositis were observed in 42.6% in the Z-BEAM group Vs 12.7% in the BEAM group (p<0.0001). Admissions to intensive care unit were more frequent in the Z-BEAM group (20.6%) than in the BEAM group (7.3%), p=0.038. Transplant-related mortality (TRM) occurred in six (8.8%) patients in the Z-BEAM group and only one patient (1.8%) in the BEAM group (P=0.071). Median follow up was 73 months in the BEAM group (range 3.1–141 months) and 31 months in the Z-BEAM group (1.4–80.9 months). The 3-years OS is 80% (95%CI, 69–89%) and 78.1% (95%CI, 64.5–88%) in the Z-BEAM and the BEAM group respectively (P=0.864), and 3-years PFS was 65% (95%CI, 56–79%) and 63.4% (95%CI, 51–77%) respectively (P=0.539). Outcome was not statically different with Age (>60 y.o), histological subtype, first line treatment Vs second line, or IPI (0–1 Vs 2–3). In a subset analysis of the Z-BEAM group, female gender was associated with worse outcome; 3 years-OS was 69% (95%CI, 48–85%) in female and 93% (95%CI, 79–98%) in male (p=0.042); 3 years-PFS was 54% (95%CI, 34–73%) in female and 81% (95%CI, 65–91%) in male (p=0.032). Those results may be linked to a higher TRM, 23.1% Vs 0% (P=0.002), more respiratory complications 23.1% Vs 4.8 % ( P=0.047) and more admissions to intensive care unit 46,1% Vs 2 % (P< 0.0001) in female than in male group respectively.

Z-BEAM is possibly as effective as BEAM alone as a conditioning regimen for ASCT with an increased toxicity. Surprisingly, our series report for the first time an increased toxicity and TRM in female. A longer follow up is needed to asses this results.

No relevant conflicts of interest to declare.