Is photopheresis treatment of choice for cgvhd?

Transcription

1 Is photopheresis treatment of choice for cgvhd? Univ. Klinik für Innere Medizin I Hildegard Greinix Medical University of Vienna Vienna, Austria

2 Treatment Challenges of Chronic GvHD Control of GvHD activity TRM due to infections and organ toxicities Impaired quality of life due to disabilities Side effects of immunosuppression Steroid-sparing important for less toxicity, fewer infections, improved survival Relapse

3 Extracorporeal Photopheresis

4 ECP in Refractory Chronic GvHD High response rates Skin 40-90%, liver 0-80%, mucosal 20-90% Excellent safety profile ECP as frequently applied salvage therapy in adults and childrenwithsteroidrefractory cgvhd Randomized Study Flowers MED et al, Blood 2008;112:

5 Phase II Study of ECP in Steroid-Refractory/Dependent/Intolerant cgvhd Resolution or Improvement in Extracutaneous cgvhd at Week ECP w12 ECP w24 non-ecp w oral liver lungs eye joint GI Flowers MED et al, Blood 2008;112:

6 Phase II Study of ECP in Steroid- Refractory/Dependent/Intolerant cgvhd CR+PR w12 during standard non-ecp therapy and after cross-over to ECP CR+PR in early vs. late use of ECP Original Randomized Non ECP % 53% % 0 Oral 30% Mucosa 43% 50% 21% Liver Cross over Open label ECP Study 27% 7% Ocular 12% Joint 36% % 70% Oral Mucosa Week 24 29% 50% Liver Week 24 26% 47% Ocular Week 24 Original Randomized ECP Crossover Open Label ECP Study 50% 42% Joint Week 24 CR+PR of skin by investigator assessment in 9 (31%) pts at week 24. 8/24 (33.3%) pts achieved >50% reduction in steroid dose at week 24. Similar response rates in skin and extracutaneous cgvhd compared with original ECP cohort despite longer duration of cgvhd. Greinix H et al, BBMT 2011

7 Results of German/Austrian/Swiss Survey on Salvage Therapy of Chronic GvHD

8 ECP in Steroid-Refractory BOS after HCT

9 Bronchiolitis Obliterans Syndrome New onset of noninfectious progressive airflow obstruction Almost exclusively associated with cgvhd Incidence: 2-26% Poor prognosis: 5-yr OS 10-20% Initial therapy: protracted steroids 8-20% improvement; stable disease = success No controlled studies available

10 ECP in BOS after HCT Author No pts Prior tx Response (%) Comment Child 99 5 P,CNI,T,A,PUVA 2 PR (40) Dall Amico CR,2 PR (54) Messina CR,2 PR (43) IS, OS Couriel P,CNI, MMF, I, D, S, PUVA 1 CR,5 PR (54) DC IS Flowers (22) Randomiz. Lucid (67) Med. 24 d to response Greinix (75) Cross-over 100 pts published: 51 (51%) responded; 14 CR, 20 PR, 17 improved.

11 Treatment Challenges of Chronic GvHD Control of GvHD activity TRM due to infections and organ toxicities Impaired quality of life Side effects of immunosuppression Steroid-sparing important for less toxicity, fewer infections, improved survival Relapse

12 Steroid-Sparing Effect of ECP in Chronic GvHD Author No pts ORR% Steroidsparing OS n (%) Greinix /15 (93) Salvaneschi /14 (79) Messina /44 (77) Apisarnthanarax /32 (59) Foss /25 (60) Rubegni Couriel /71 (18) Greinix /47 (89) Flowers vs 10 Jagasia Greinix

13 Phase II Study of ECP in Steroid-Refractory/Dependent/Intolerant cgvhd TSS and Steroid Response to ECP Week 12 Week 24 Parameter ECP Non- ECP P value ECP Non- ECP Median % change in TSS N/A No (%) pts > 50% reduction in steroid dose No (%) pts > 50% steroids and > 25% TSS No (%) pts > 50% steroids and final steroids < 10 mg/day 12 (25) 6 (12.8) Flowers MED et al, Blood 2008;112: (39.6) N/A 4 (8.3) (22.9) N/A 10 (20.8) 3 (6.4) (35.4) N/A

14 Impact of ECP on Survival

15 Improved Survival of ECP Responders Messina et al, Brit Haematol 2003 Couriel et al, Blood 2006 High efficacy of ECP with excellent safety profile Steroid-sparing effect of ECP: complications, NRM

16 Safety Excellent safety profile Reported adverse events Hypotension in 2-4% Dizziness in up to 4% Chills in up to 5% Anemia Catheter-related side effects CVC-related infections Venous thrombosis

17 Efficacy of ECP is not a result of generalized immunosuppression

18 Efficacy of ECP is not a result of generalized immunosuppression No increase of opportunistic infections or relapse during ECP Improvement in immune reconstitution after ECP in experimental allo BMT No suppression of T-or B- cell responses to novel or recall antigens after ECP Suchin et al, J Am Acad Dermatol 1999 Gatza et al, Blood 2008

19 Wolff et al BBMT 2011 Therapy Rec. Evid. Comment Steroid B III-1 Serious side effects Photopheresis C-1 II Steroid-sparing, excellent safety profile mtor Inhib. C-1 III-1 TAM with CNI Cyclosporin / FK506 C-1 III-1 Spare steroids MMF C-1 III-1 viral infections, GI toxicity Imatinib C-2 III-1 Best in sclerodermoid GvHD and BO Rituximab C-2 II Effective in autoab mediated diseases Total nodal Rx C-2 III-2 Best in fasciitis and mucocutaneous cgvhd

20 ECP in chronic GvHD Conclusions Goal in chronic GvHD Achieved Efficacy in skin GvHD as salvage Efficacy in extracut. GvHD as salvage Steroid-sparing effect D.C. other immunosuppressants Excellent safety profile GVL effect unimpaired Immune reconstitution unimpaired Optimal schedulle and duration??? Efficacy as upfront therapy???

21 GvHD Study Group Vienna BMT Unit R. Weigl P. Kalhs W.Rabitsch Z. Kuzmina C. Zielinski Dept. Immunology W.F. Pickl U. Körmöczy Dept. Dermatology R. Knobler G. Stary U. Just A. Tanew Dept. Transfusion Medicine N.Worel G. Leitner Dept. Gastroenterology - G. Vogelsang - E. Penner Dept. Pulmonology - V. Petkov