Allogeneic SCT for. 1st TKI. Vienna Austria. Dr. Eduardo Olavarría Complejo Hospitalario de Navarra

Transcription

1 The International Congress on Controversies in Stem Cell Transplantation and Cellular Therapies (COSTEM) Berlin, Germany September 8-11, 2011 Vienna Austria Allogeneic SCT for CML Allogeneic after failure SCT for to CML 1st after line failure TKI to 1st TKI Dr. Eduardo Olavarría Complejo Hospitalario de Navarra

2 What is 1st line TKI? Traditional definition: Imatinib Alone In combination New definition: Nilotinib or Dasatinib Today s definition: Judicious use of all available TKIs

3 What is 2nd line TKI? Traditional definition : Imatinib Alone In combination A different TKI from the one you tried first New definition: Nilotinib or Dasatinib Today s definition: Judicious use of all available TKIs A different therapy: NOT a TKI Allogeneic SCT

4 Allo-SCT for CML in Europe CML-CP allo CML non 1st CP allo CML-CP auto CML non 1st CP auto Updated from Gratwohl A, et al. Haematologica 2006;91:

5 SCT for CML: the EBMT score 1.0 CML 0.8 Score 0 Survival Score 1 Score 2 Score 3 Score 4 Score Score 6-7 Yrs After Transplantation Prognostic factors for survival (defined before SCT): Age Disease phase Disease duration Histocompatibility Patient/Donor gender Gratwohl A, et al. Haematologica. 2006;91:

6 Overall survival after diagnosis of BC German CML I, II and III- A studies (n = 605) CA : Dasatinib (n = 156) SCT in BC between (n = 400) 1,00 0,80 0,60 0,40 Unrelated Donor 0,20 Sibling Donor 0, Saglio et al. Blood (ASH Annual Meeting) 2008; 112: Abst Hehlmann et al. Haematologica 2008; 93: Courtesy of CLWP-EBMT

7 Survival after SCT for early CML-CP Survival of patients in early first chronic phase according to the revised chronic phase risk score (N=2049) 1.0 Survival Risk score 0.0(0 2 points per category) Age, years: 0<30 (0); (1); >40 2 (2) Donor: sibling (0); unrelated (2) Years Interval diagnosis SCT: <1 year (0); >1 year (1) Sex match: female male (1); all other (0) Passweg JR, et al. Br J Haematol 2004;125:

8 Progress in allo-sct for CML Overall survival among good risk patients (score=0 1) N = N = N = 594 Gratwohl A, et al. Haematologica 2006;91:

9 Progress in allo-sct for CML EBMT % at 5 years (95% CI 83 93%) Patients previously treated with imatinib Probability of survival of 214 patients with CML and an allo-hsct from their HLA identical sibling and an EBMT risk score of 0 2 Courtesy of Dr Heim (CLWP-EBMT).

10 Allo SCT for CML in the Imatinib Era 1.0 Survival Probability Elective, n = 19, 3-yr survival: 88% Imatinib failure in 1 CP, n = 37, 3-yr survival: 94% Advanced phase, n = 28, 3-yr survival: 59% Months After Transplantation Saussele S, et al. Blood. 2010;115:

11 Impact of previous imatinib on SCT Lee SJ, et al. Blood 2008;112:

12 Survival in post-sct CML relapse 1.0 treated with imatinib Probability of Survival CP (n=51) AP (n=31) BC (n=46) p< Months Olavarria E, et al. Leukemia 2003;17:

13 Prophylactic imatinib post RIC-SCT: Chimerism analysis Whole Blood T-cell fraction 100% 80% Patients (%) 60% 40% 20% 0% Post SCT Post Imatinib Post DLI Post SCT Post Imatinb Post DLI 100% Donor 90 99% Donor Mixed Updated from Olavarria et al, Blood 2007; 110:

14 Possible role of SCT in CML in 2011 After failing BCR-ABL inhibitors Imatinib failure, suboptimal response, intolerance (ELN guidelines) Failure to 2 nd -generation BCR-ABL inhibitor (instead or after Imatinib) Resistance to BCR-ABL inhibitors associated with the T315I mutation

15 Overall Survival after failing BCR-ABL inhibitor therapy due to T315I mutation Probability of overall survival Log-rank: p<0.001 Months since T315I detection Nicolini F, et al. Blood Accepted.

16 Indications for SCT as 2 nd -line treatment for CML After judicious use of all available TKIs, SCT is to be considered as preferential therapy in patients not achieving a CCyR if: EBMT score of 0-2 EBMT Score 3 5 and 1 of the following: Clonal evolution ABL mutations resistant to 2 nd -generation BCR-ABL inhibitor Failure to achieve at least minor CyR to 1 st -line Imatinib High Sokal score at diagnosis Loss of CHR and MCyR after initial response Provisional. Unpublished. Olavarria E.

17 Indications for SCT as 2 nd -line treatment for CML Second line therapy for patients who relapse after an initial response to TKI should be based on the risk of the transplant (EBMT risk score) and the likelihood of responding long-term to a different TKI. For patients who relapse after TKIs, SCT is to be considered as preferential therapy if: EBMT Score 0 2 and 1 of the following: Lack of CCyR (at least MCyR) after 6-12 months of 2 nd -line TKI Clonal evolution EBMT Score 0 5 and 1 of the following: AP at diagnosis or during 1 st -line BCR-ABL inhibitor therapy ABL mutations resistant to 2 nd -generation BCR-ABL inhibitor Failure after all 3 BCR-ABL inhibitors currently available Regardless of EBMT score if: Progression to BP (after attempting to achieve a 2nd CP) Provisional. Unpublished. Olavarria E.

18 THANK YOU! Allo-SCT Investigational Agents Imatinib Nilotinib Dasatinib