1. A new possible conditionning regimen before Autologous Stem Cell Transplantation for refractory high-grade lymphoma Z-BeEAM (Ibritumomab tiuxetan, Bendamustine, Etoposide, Cytarabine, Melphalan)
TARDY M., GASTAUD L., OJEDA-URIBE M., BOSCAGLI A., CARUSO S., SKAF R., GUTNECHT J., THYSS A., PEYRADE F.

2. Indications of Autologous Stem Cell Transplantation (ASCT)
Relapsing follicular lymphoma
Relapsing diffuse large B cell lymphoma
Mantle cell lymphoma
=> High Dose chemotherapy followed by ASCT
BEAM is most commonly used regimen before ASCT :
Carmustine (300 mg/m² at day 1)
Etoposide (200 mg/m² every 12H for 4 days)
Cytarabine (200 mg/m² every 12H for 4 days)
Melphalan (140 mg/m² at day 5)
For chemosensitive lymphoma
Mills W. et al., BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin’s lymphoma, JCO, 1995; 13:

3. Replacement of carmustine
BeEAM regimen :
Bendamustine (180 mg/m² at day 1)
Etoposide (200 mg/m² every 12H for 4 days)
Cytarabine (200 mg/m² every 12H for 4 days)
Melphalan (140 mg/m² at day 5)
=> Safe and effective
Visani G. et al., Bendamustine, etoposide, cytarabine, melphalan, and autologous stem cell rescue produce a 72% 3-year PFS in resistant lymphoma, Blood, 2014;124:

4. Use of BEAM as conditionning regimen Shortage of carmustine BeEAM
(Mills, 1995)
Shortage of carmustine
BeEAM
(Visani , 2014)
1995
2004
2012
2013
2014
Zevalin® (Ibritumomab Tiuxetan): Approval in Europe

5. Ibritumomab tiuxetan (Zevalin ®)
Action mode
Monoclonal anti-cd20 antibody
Chelator
Radioisotope
Indications
Low-grade or follicular Lymphoma relapsing during or after treatment
Newly diagnosed follicular Lymphoma in response after initial anticancer therapy

6. Use of BEAM as conditionning regimen Shortage of carmustine BeEAM
(Mills, 1995)
Shortage of carmustine
BeEAM
(Visani , 2014)
1995
2004
2012
2013
2014
Zevalin® (Ibritumomab Tiuxetan): Approval in Europe
Z-BEAM
(Shimoni , 2012)
P = 0,05
Z-BEAM group : 22 patients
BEAM group : 21 patients
Shimoni A. et al., A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as conditioning regimen before ASCT , Cancer, 2014;118:

7. Use of BEAM as conditionning regimen Shortage of carmustine BeEAM
(Mills, 1995)
Shortage of carmustine
BeEAM
(Visani , 2014)
1995
2004
2012
2013
2014
Addition of Ibritumomab tiuxetan to high dose chemotherapy before ASCT is safe and effective
Zevalin® (Ibritumomab Tiuxetan): Approval in Europe
Z-BEAM
(Shimoni , 2012)
P = 0,05
Z-BEAM group : 22 patients
BEAM group : 21 patients

8. Ibritumomab tiuxetan + BeEAM before ASCT?
Safe
Feasible
Effective ? ? ?

9. Patients and disease characteristics
Number of patients
Median age: years (median range)
60 (51-66)
Anatomopathology:
Follicular lymphoma
Mantle lymphoma
Diffus large B cell lymphoma 1 2 3
Gender:
Male
Female 5
Performans Status (PS):
>0 6
Number of previous chemotherapies:
Disease status at transplantation:
Complete response
Partial response
PET-CT before transplantation:
Negative
Positive
Median time between diagnosis or relapse and ASCT (months)
8.5 (7-12)
Retrospective study
2 centers in France
Tardy et al., Z-BeEAM before ASCT is safe and efficient for refractory large B cell lymphoma, Experimental Hematology and Oncology, 2015:4-18.

10. Conditionning regimen before ASCT
Rituximab (250 mg/m²) + Zevalin ® (1200UI)
Rituximab
(250 mg/m²)
BeEAM regimen
Day -21
Day -14
Day -7 to Day - 2
Day 0
Stem cells reinjection (IV)

11. Engrafment characteristics
Tardy et al., Z-BeEAM before ASCT is safe and efficient for refractory large B cell lymphoma, Experimental Hematology and Oncology, 2015:4-18.

12. Non hematologic toxicities
Renal toxicity
Tardy et al., Z-BeEAM before ASCT is safe and efficient for refractory large B cell lymphoma, Experimental Hematology and Oncology, 2015:4-18.

13. Efficiency After a median follow-up time of 5 months (1st March 2015)
=> All patients alive, in complete response (clinical, biologic and radiologic on PET-CT) and with a good hematologic recovery
After a median follow up of 20,6 months (1st June 2016)
=> 1 lost to follow up
=> 5 alive :
3 complete response
2 patients relapsed after a median PFS of 16 months
Tardy et al., Z-BeEAM before ASCT is safe and efficient for refractory large B cell lymphoma, Experimental Hematology and Oncology, 2015:4-18.

14. Conclusion
‟ Phase I” study to evaluate Z-BeEAM as a conditionning regimen before ASCT
NO unexpected toxicities
NO increase in the risk of Grade III/IV mucositis
NO long term toxicities
Efficient

15. Z-BeEAM is safe and effective before ASCT

16. Thank you for your attention