Haploidentical Transplants for Lymphoma. Andrea Bacigalupo Universita Cattolica Policlinico Gemelli Roma - Italy

Transcription

1 Haploidentical Transplants for Lymphoma Andrea Bacigalupo Universita Cattolica Policlinico Gemelli Roma - Italy

2 HODGKIN NON HODGKIN

3 Non Myelo Ablative Regimen Luznik L et al BBMT 2008

4 Comparison of Outcomes of HLA-Matched Related, Unrelated, or HLA-Haploidentical Related HSCT following Nonmyeloablative Conditioning for Relapsed or Refractory Hodgkin Lymphoma Burroughs et al. BBMT 2008 HLA-Matched Related n =38 Unrelated n =24 HLA-Haploidentical Related n = 28 Previous autologous HSCT: 92% Median follow up: 25m

5 Outcomes according to different donor types SIB MUD HAPLO 2 yy OS 53% 58% 58% 2 yy EFS 23% 29% 51%* 2 yy rel 56% 63% 40%* 2 yy NRM 21%* 8% 9% *=statistically significant differences Burroughs et al. BBMT 2008

6 acute GvHD II-IV AM Raiola et al, BMT 2014 N=26 GE-SM and Humanitas Mi 24% chronic GvHD 9% Non relapse mortality Relapse 31% 4% Fig.2

7 Clinical characteristics 68 HD: GE SM haplo other HD Age 30 (18-59) 30 (18-43) Donor haplo 39 0 SIB/1Agmm/UD/CB 13/4/8/4 Act disease 77% 82% Year Tx (09-14) (02-12) FU surv.pts ( ) (8-3881)

8 Acute GvHD II-III Chronic GvHD mod-severe P=0.4 HAPLO n=39 Other n=29 18% 11% HAPLO n=39 Other n=29 17% 14%

9 HD: Transplant related mortality (TRM) P=0.04 Other n=29 27% HAPLO n=39 5%

10 Hodgkin: relapse P=0.9 56% HAPLO n=39 Other n=29 49%

11 Hodgkin: survival HAPLO: Low TRM Rescue of relapse HAPLO n=39 74% Other n=29 37% P=0.0007

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13 Regimen for relapsed HD Chemo Gemcitabine n=3 Bendamustine+ Rituximab n=7 N courses before DLI = 3 (1-4) Interval chemo- DLI =9 days (5-21) N DLI given 1-4; median dose 1x10^5 CD3/kg (range 1x10^4-1x10^7/kg) GvHD grade II = 1 (10%); DLI-death =0

14 RESPONSE to DLI for 10 relapsed HD 4 CR (PET neg) (40%) 3 PR 1 stable disease 2 progression Of the 7 responders 4 alive DF Survival 8/10 (18 mm from DLI 4-34)

15 HODGKIN # Excellent survival with HAPLO grafts # very low TRM # Relapse can be rescued in 40% Can relapse be predicted?

16 PET scans pre transplant in 39 HD undergoing HAPLO Tx chemosensitive chemorefractory P value N. of patients PET pre Tx -/+ 13 / 10 0 Median age, yy 30 (18-50) 32 (23-59) 0.6 N.Lines of therapy 5 (3-8) 5 (3-12) 0.7 Interv Dx-BMT Previous auto 100% 100% Prev Auto+Allo 0 2 patients Brentuximab pre Tx 8 3 Engraft day PMN (14-26) 18 (13-25) 0.6 Acute GvHD II-IV 24% 18% 0.1 Chronic GvHD 19% 18% 0.9 Median days FU (range) 686 ( ) 442 ( ) 0.2

17 % of patients relapse chemosensitve chemorefractory HD: Disease free survival Overall Survival Chemosensitive, n=23 87% Chemosensitive, n=23 61% Chemorefractory, n=13 84% P= P=0.8 Chemorefractory, n=13

18 HODGKIN It is crucial to bring patients to Allo TX in remission= PET neg # brentuximab # check point inhibitors Post-transplant therapy may be relevant (ipilimumab: Dana Farber data)

19 HODGKIN NON HODGKIN

20 2091 Outcomes Of Nonmyeloablative (NMA) Haploidentical Blood Or Marrow Transplantation (haplobmt) With High-Dose Posttransplantation Cyclophosphamide (PT/Cy) dor older patients Baltimore, aged 50-75; NMA conditioning; n=273

21 Myelo Ablative Regimen Raiola et al BBMT 2013; 19:117 BM CY CY Thiotepa 5 mg /kg day -6-5 tot 10 mg/kg Fludarabine 50 mg/m^2 day tot 150 mg/m^2 Busulfan 3.2 mg/kg q24h day tot 9,6 mg/kg

22 Myelo Ablative Regimen Raiola et al BBMT 2013; 19:117 BM CY CY Thiotepa 5 mg /kg day -6-5 tot 10 mg/kg Fludarabine 50 mg/m^2 day tot 150 mg/m^2 Busulfan 3.2 mg/kg q24h day tot 9,6 mg/kg

23 Haplo transplants with PT-CY: MA regimens 165 = AML+ALL+RAEB CR1 49 (17-69) CR2 44 (17-67) advanced, 58 (19-74) CR1, n=79 77% CR2, n=49 50% advanced, n=108 38% P<

24 Clinical chacteristics NHL haplo other n= CY-TBI 23% 47% TBF 77% 2% RIC 51% AGE 47 (22-63) 44 (19-65) Year Tx >CR2 79% 76%

25 Donor chacteristics NHL haplo other n= SIB ag mm 0 4 UD 0 19 CB 0 5 HAPLO 17 0

26 Clinical chacteristics NHL in the HAPLO Histology CR DLBCL 23% 20% FC (III) 47% 30% LBL 23% 75% PTCL 7% 0%

27 NHL: Transplant related mortality (TRM) P=0.02 Other n=49 36% HAPLO n=17 5%

28 NHL: relapse P=0.1 HAPLO n=17 Other n=49 29% 22%

29 Overall Survival, NHL HAPLO n=17 70% Other n=49 50% P=0.1

30 NON HODGKIN LYMPHOMA # low TRM # same relapse # OS not inferior to other donors What abou stem cell source?

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32 BBMT 2015 in press TBI 1500 rads + FLU 25 x3 Day 0 unmanipulated G-PB (CD34 5x10^6/kg) CY 50/kg day +3+4 Day 5: FK (target 5-15 n/ml) + MMF 15 mg/kgx3

33 30 patients in CR; age 46 (24-60) donor = familt HAPLO mismatched SC source : G-PB 40% 23% 56% 22% 10%

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35 28 patients ; age 47 (21-65) ; AML (15) ALL (10) other (3) All patients were in CR at the time of transplant (19 CR1)

36 UN-MANIPULATED HAPLO GRAFTS: myeloablative regimens SC Age Rem N GvHD cgvhd TRM III-IV BM+PB ATG 25y CR+ad % 53% 18% GBM ATG 37y CR+ad 80 5% 17 36% PB + Ly 2step 47y CR 28 4% 22% 4% G-PB PTCY 46y CR 30 23% 56% 3% G-PB ATG 25y CR 99 17% 41% 30% BM PTCY 47y CR+Ad 231 3% 16% 14%

37 STEM CELL SOURCE FOR HAPLO BM PREFERRED PB ACCEPTABLE if NMA if MA GvHD ++ counteracted by ATG + PT-CY?

38 BM (w/wo G) and HAPLO = a standard (Baltimore- Pecking) PB : trying to prove it can also work Why should we go through the hassle? # less relapse? (meta-analysis of randomized trials)

39 CML 50% of pts CML 10% of pts

40 A 10-year estimate 28.3% BMT 13.0% PBPCT p log rank = 0.13 (HR 0.61; CI 95% ) B 10-year estimate 62,3% BMT 47.1% PBPCT p log rank = 0.16 (HR 0.67; CI 95% ) Time after transplantation (months) Time after transplantation (months) C C D 10-year estimate 40.2% BMT 48.5% PBPCT p log rank = 0.81 (HR 0.93; CI 95% ) 10-year estimate 46.5% BMT CR1, 39.0% BMT > CR1 43.5% PBPCT CR1, 36.5% PBPCT > CR1 p log rank = 0.81 Time after transplantation (months) Time after transplantation (months) Friedrichs et al., Lancet Oncol. 2010; 11: 331

41 CONCLUSION HAPLO for LYMPHOMA # HD : low TRM; same REL; improved OS # NHL: low TRM; same REL; samos # relevant variables:.type of conditioning. SC source.gvhd proph.disease phase (risk)

42 Thank you for your attention