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Andre Goy, MD Cancer Center Director Lymphoma Division Head John Theurer Cancer HUMC, NJ Chief Science Officer Research / Innovation RCCA Professor.

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Presentation on theme: "Andre Goy, MD Cancer Center Director Lymphoma Division Head John Theurer Cancer HUMC, NJ Chief Science Officer Research / Innovation RCCA Professor."— Presentation transcript:

1 Andre Goy, MD Cancer Center Director Lymphoma Division Head John Theurer Cancer Center @ HUMC, NJ Chief Science Officer Research / Innovation RCCA Professor of Medicine at Georgetown MCL: Should all Eligible patients with MCL receive HDT-ASCT upfront? agoy@hackensackUMC.org

2 MCL – Clinical Course – EU MCL Network CR-CRu 20-25%

3 MCL: High-Dose Therapy as Consolidation CHOP-> ASCT >CHOP-IFN 69 / 75 pts Dreyling M, et al. Blood. April 2005 ResponseIFN arm ASCT armp value Med DOR3.7y1.6 y0.0004 ITT med TTF1.4y2.6y0.0001 OS5.4 y7.50.075

4 MCL – Management – 4 Phases Induction Consolidation Maintenance Salvage BEFORE CVP, CHOP, FC, CBL Nothing or HDT-ASCT Nothing or IFN More chemo…? Very short response to salvage chemo even with HDT-ASCT More chemo…? Very short response to salvage chemo even with HDT-ASCT Frequent chemoresistance

5 MCL – Management – 1 st Challenge Decide when to treat and recognize “indolent” MCL MIPI Ki-67 Hoster, Blood Jan 2008 Determann, Blood Dec 2007 Indolent?

6 MCL – Management – 1 st Challenge Decide when to treat and recognize “indolent” MCL Fernandez, Can Res, Feb 2010

7 MCL – Management – 1 st Challenge Recognize “indolent” MCL iMCL vs. cMCL Fernandez, Can Res, Feb 2010

8 MCL – Important Steps – Induction Therapy Geisler, Leuk Lymphoma, Aug 2009

9 MCL – Important Steps – Rituximab Impact Meta analysis showed > OS with R-chemo Schulz, J Natl Cancer Inst, May 2007 Griffith et al, Blood 2011; SEER data Elderly “real world” / TTNT med 11 ms, med OS 27 vs 37 ms

10 MCL – Important Steps- Rituximab / R-chemo ResponseCHOPR-CHOPp ORR74%94%0.005 CR7%34%0.00024 TTF14 ms21 ms0.01 Lenz, JCO, March 2005; Hoster ASH 2008 Schulz, J Natl Cancer Inst, May 2007; Griffith et al, Blood 2011; SEER data PFSTTNT OS Rituximab increases ORR, CR rate but med PFS @2y 25%!!! 59 / 62 pts

11 MCL: ASCT remains Relevant in R-chemo Era ASCT vs. Maint IFN in R-chemo era Hoster, ASH 2008 ASCT remains relevant in the R-chemo era Pooled younger / older HDT /vs. stand + maint IFN

12 DIT/ASCT Have Also an Impact Outside of Clinical Trials 167 MCL pts NCCN database – frontline R-chemo - NOT on trial LaCasce A, et al. Blood, 2012 Mar 1;119(9):2093-9 OS K-Mp R-HyperCVAD vs R-CHOPP <.04 R-CHOP/ASCT vs R-CHOPP <.20 R-HyperCVAD vs R-CHOP/ASCTTP =.64 PFS OS 3y PFS R-CHOP 18% 3 times < to any dose- intensive strategy (56-58%) When pooling DI-HDT pts / R-CHOP >>> PFS and OS (p=0.001)

13 MCL - Important Steps - Induction Impact Prior to ASCT (R)-CHOP-DHAP  ASCT Tripled CR rate after R-DHAP (12% vs. 61%) Med EFS: 84 ms vs. 51 ms prior to rituximab EFS Delarue, Blood Jan 2013 OS

14 MCL – Important Steps- Induction Impact Prior to ASCT Geisler, Blood, July 2008 60y / same benefit MCL 2: 55% CR-CRu post induction

15 MCL – Important Steps- Induction Impact Prior to ASCT Geisler, Blood Feb 2010 Geisler, Br JnlHeamatol, Aug 2012 Median follow-up of 6·5 years More than 70% of patients with low- intermediate MIPI-B were alive at 10 years Geisler, Br JnlHeamatol, Aug 2012

16 MCL - Important Steps - Induction Impact Prior to ASCT Geisler, Blood Feb 2010 - Multicenter setting - Med age 56 y (32-65) -Median OS and median response duration BOTH not reached at 10 years

17 MCL - Important Steps - R/AraC Induction Impact 1. Cortelazzo S, et al. ASH 2007. Abstract 1282. 2. Romaguera JE, et al. J ClinOncol. 2005;23:7013-7023. 4. Fayad L, et al. Clin Lymphoma Myeloma. 2007;8, Delarue, Blood Jan 2013 R-CHOP 2y PFS 25% !! StudyTherapy5-Yr EFS, % GITIL [2] (R) HDS-ASCT*61% MDACC [3,4] R-HyperCVAD60% / FFS CALGBR-Maxi CHOP-MTX / VP16-AraC/ CBV- ASCT 56% / PFS EU (GELA)R-CHOP/DHAP- TAM  ASCT 65% / TTF

18 MCL - Important Steps - R/AraC Induction Impact MCL Younger < 65 years R Dexa BEAM Cyclo TBI + Autograft P B S C harvest Ara-C, Melphalan TBI + Autograft 3-monthly follow-up 1 9 5 1317 week R-CHOP/R-DHAP alternating 3-weekly 1 9 5 1317 week R-CHOP 3-weekly 3-monthly follow-up P B S C harvest MRD MRD 2-3 monthly intervals Hermine et al, ASH 2010 abst # 110 AraC benefit confirmed in randomized trial

19 MCL - Important Steps - R/AraC Induction Impact Hermine et al, ASH 2010 abst # 110 / ASH 2012 abst # 151 months TTFT (Primary endpoint) Remission Duration after ASCT w/ med follow up 51 ms, TTF 46 vs 88 ms, p0.038 w/ med follow up 51 ms, remission duration 49 vs 84 ms, p 0.0001 212 pts R-CHOP/ 208 pts R-CHOP/DHAP No diff between arms in pts characteristics or % pts going ASCT (77% / 79%)

20 MCL - Important Steps - R/AraC Induction Impact Hermine et al, ASH 2010 abst # 110 / ASH 2012 abst # 151 HD AraC translates into > OS as well

21 MCL – Important Steps Benefit in all MIPI groups: TTF ITT Hermine O, et al. ASH 2012. Abst # 151 Ki67 in low MIPI

22 MCL – Important Steps Hermine O, et al. ASH 2012. Abst # 151

23 MCL – Important Steps Hermine O, et al. ASH 2012. Abst # 151 Remission duration based on clinical and mol response after induction

24 EU - MCL Younger Pts - Results Hermine et al, ASH 2010 abst # 110 / ASH 2012 abst # 151 R-CHOPR-DHAP PBBMPBBM 0 25 50 75 100 % MRD negative 54% 70% p = 0.04p = 0.01 36% 60% 82% 73% 87% ns * * ** Impact of ASCT on MRD status

25 MCL – Younger Pts – Frontline Summary –Arm R-CHOP-DHAP leads to > outcome TTF, DOR and now OS –Due to higher and earlier rate of CR-CRu and molecular CR in HD AraC arm POST induction ++ Med OS AraC arm NR vs 82 ms, p 0.045 ParameterR-CHOP/R-DHAPR-CHOPp CR-CRu55%40%p=0.0028 Mol CR83%51%p < 0.0001 Hermine et al, ASH 2010 abst # 110 / ASH 2012 abst # 151 Post ASCT similar CR-CRu (79/82%)

26 MCL – Important Steps – ASCT remains relevant in the R-chemo Era TTF w/ R-CHOP vs. R-CHOP/R-DHAP  ASCT Hoster, AH 2008

27 MCL – Important Steps – DIT/ASCT remains relevant in the R-chemo Era “Longest mileage” Cost

28 MCL - DIT/HDT-ASCT - Summary –Med OS improvement recognized mostly due to long unprecedented PFS > 5y with DIT and /or HDT-ASCT (40% MCL are <60y) –Achieving a deep and early response in MCL matters –A CR  translates into >> outcome –Molecular CR ++ might become new surrogate endpoint

29 MCL – DIT-ACST Remains the Best Option in R-Chemo Era –Clearly subset of MCL that are more indolent (nonnodal leukemic phase, hypermutated & SOX11 -ve) –Novel therapies very promising  Platform for combinations (improve mol CR) and /or maintenance post therapy  Alternative to chemotherapy (in elderly)

30 MCL – Management – DIT/ASCT Fit Pts Induction NOW and FORWARD Mol CR as a new endpoint? Beyond standard chemo in MCL Induction: R-chemo with cytarabine Consolidation Still longest PFS Will MOL CR early still need ASCT? Maintenance Still late relapses Novel therapies? PCR based? Novel therapies? PCR based? Salvage Role of HDT/ASCT debated Novel therapies combos? Mini allo? CAR? Novel therapies combos? Mini allo? CAR?

31 Thank you! agoy@HackensackUMC.org


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