Plerixafor: mechanism of action

Transcription

1 Plerixafor and GCSF in patients with lymphoma and multiple myeloma previously failing mobilization with G- CSF +/- chemotherapy for autologous hematopoietic stem cell mobilization: The Austrian experience on a named patient program Nina Worel Dept. for Bloodgroup Serology and Transfusion Medicine Medical University of Vienna Plerixafor: mechanism of action SDF-1α and CXCR4 play key regulatory roles in stem cell trafficking to, and retention by the bone marrow. Plerixafor blocks the CXCR4/SDF-1α interaction, releasing stem cells from the bone marrow into the circulating blood. Lapidot T and Petit I, Exp Hematol. 2002; Martin et al, BJH

2 Known risk factors for suboptimal mobilisation Age > 60 years 1 Underlying disease 1,2 Previous RT and chemotherapy 1,2 Multiple chemotherapy cycles 1,2 Previous treatment with melphalan, carmustine or fludarabine 1,2 Novel induction strategies (e.g. lenalidomide in MM) 3 Poor or failed mobilisation is often defined as a collection of < cells/kg 1,2 1. Stiff. Bone Marrow Transplant 1999;23(suppl 2):S29 S Micallef et al. Hematol J 2000;1: Rajkumar et al. Blood 2005;106: NPP Inclusion and Exclusion Criteria Inclusion Criteria: - MM, NHL, Hodgkin s disease - Failed previous stem cell collection - Age: 18 to 70 years - WBC > 3.0 x 10 9 /L; ANC > 1.5 x 10 9 /L; PLT > 100 x 10 9 /L - LFTs < 2.5 ULN - Serum creatinin 1.5 mg/dl Exclusion Criteria: - Acute and chronic leukemia, myelodysplasia - Acute infection - Brain metastasis - Pregnancy Calandra G, et al. Blood. In submission 2

3 Patient Characteristics (n=27) Male/Female Age in years Diagnosis MM NHL HD Time since diagnosis in months # prior CHT cycles Patients with prior radiotherapy # previous HSC mobilizations attempts 9/18 58 (19-70) 8* 17* 2 25 (2-166) 8 (3-27) 3 1 (1-8) * 1 MM + 2 NHL pts. ad 2 cycles with plerixafor median (range) Results (n=27 pts) Median (Range) Day 4 before Plerixafor Day 5 Plerixafor Number of CD34 + cells x10 6 /kg Number of HSC collections/patients Enough cells for HSCT n (%) CD34+ cells 5.6 (0-12) /µl 12.9 (0-74.6) /µl 2.8 ( ) 2 (1-4) 17 (63%) 3

4 CD34 cells increase plerixafor CD34/µl CD34 x10 6 /kg day 4 before 1st Plerixafor day 5 1st Plerixafor day 6 2nd Plerixafor day 7 3rd Plerixafor day 8 4th Plerixafor >2 x10 6 CD34+ /kg plerixafor + G-CSF 63% overall re-mobilization success rate % 60 75% 40 53% 20 0 NHL (n=17) MM (n=8) HD (n=2) 4

5 Most Common Adverse Events (%) Gastrointestinal Disorders Diarrhea 4 (14) Nausea, Vomiting 3 (10) Abdominal pain 2 (7) Administration Site Conditions Injection site erythema 5 (16) *Mobilisation and treatment/ apheresis phase DiPersio et al. J Clin Oncol 2009; 27: Outcome HSCT (n=13) MM / NHL HD M / F CD34 x10 6 /kg Day ANC > 0.5 G/l Day Plt > 20 G/l RBC Units Plt Units 6/ / ( ) 12 (9-16) 15 (9-38) 2 (0-8) 2 (0-13) 5

6 Summary The safety of plerixafor has be shown in randomised Phase III trials. Plerixafor + G-CSF offers the possibility to collect sufficient numbers of CD34+ cells in poor mobilizing patients. Side effects of plerixafor are restricted to gastrointestinal problems (nausea, vomiting, diarrhea) and erythema at the injection site. Transplantation of plerixafor mobilized CD34+ cells enables comparable engraftment time and graft durability compared to transplantation of CD34+ cells collected G-CSF ± CHT mobilization. Co-authors Medical University of Vienna - H. Greinix - P. Kalhs - N. Worel Medical University of Graz - K. Rosskopf - P. Neumeister - W. Linkesch Medical University Salzburg - K. Namberger - G. Russ Medical University Innsbruck - D. Nachbaur Elisabethinen Hospital Linz - H. Kasparu Wilhelminen Hospital Vienna - N. Zojer Hanusch Hospital Vienna - E. Schlögl St. Anna Childrens Hospital - V. Witt Hospital Leoben - F. Keil 6