Roche Holding Ltd · SIX:RO

Roche — ICML 2021

20 slides from Roche's conference presentation, 2021

  1. Slide 1: Genetic markers and outcome with front line obinutuzumab plus either chlorambucil or venetoclax

    Genetic markers and outcome with front line obinutuzumab plus either chlorambucil or venetoclax - updated analysis of the CLL14 trial. Eugen Tausch, Christof Schneider, Deyan Yosifov, Sandra Robrecht, Can Zhang, Othman Al-Sawaf, Barbara Eichhorst, Anna-Maria Fink, Karl-Anton Kreuzer, Johannes Bloehd

  2. Slide 2: COI: Eugen Tausch

    COI: Eugen Tausch (Advisory board, Travel support and Speakers Bureau: Abbvie, Roche, Janssen-Cilag)

  3. Slide 3: CLL14: G-Clb vs. Ven-G in untreated patients with CLL and relevant comorbidities

    CLL14: G-Clb vs. Ven-G in untreated patients with CLL and relevant comorbidities Population: • Untreated CLL n=432 with “active disease” GClb • Median Age 72 years, CIRS score 8, Creat Clear 66.4m CLL14 • Randomized into VenG • 12 cycles Obinutuzumab + Chlorambucil (GClb) • 12 cycles Obinutuzumab +

  4. Slide 4: CLL14: G-Clb vs. Ven-G in untreated patients with CLL and relevant comorbidities

    CLL14: G-Clb vs. Ven-G in untreated patients with CLL and relevant comorbidities Population: • Untreated CLL n=432 with “active disease” GClb • Median Age 72 years, CIRS score 8, Creat Clear 66.4m CLL14 • Randomized into VenG • 12 cycles Obinutuzumab + Chlorambucil (GClb) • 12 cycles Obinutuzumab +

  5. Slide 5: Incidence of aberrations, mutations and IGHV status

    50% Incidence of factor minor 25% Incidence of aberrations, mutations and IGHV status major 1 0 0 0 0 0 5 5 5 5 5 5 5 5 5 5 5 5 5 0 0 0 1 1 0 0 0 0 5 5 5 5 5 5 5 5 5 5 5 5 5 0 0 0 0 1 0 0 0 0 5 5 5 5 5 5 5 5 5 5 5 5 5 0 0 0 0 1 0 0 0 0 5 5 5 5 5 5 5 5 5 5 5 5 5 0 0 0 0 1 0 0 0 0 5 5 5 5 5 5 5 5 5 5

  6. Slide 6: IGHV mutation status and PFS

    IGHV mutation status and PFS 1.0 Prognostic impact of IGHV VenG - IGHVmut VenG- IGHVunm VenG- IGHVmut HR 2.14 (95%CI 1.15-3.98) 0.8 GClb– IGHVunm GClb – IGHVmut HR 3.07 (95%CI 2.07-4.53) Cum Survival 0.6 IGHV status is a prognostic marker in CLL14. VenG - IGHVunm 0.4 GClb - IGHVmut VenG vs. GClb in

  7. Slide 7: Del(17p) and PFS

    Del(17p) and PFS Prognostic impact of del(17p) VenG- del(17p) VenG, no del(17p) VenG- no del(17p) HR 3.19 (95%CI 1.66-6.14) GClb– del(17p) HR 3.15 (95%CI 1.77-5.62) GClb – no del(17p) del(17p) is a prognostic marker in CLL14. VenG- del(17p) GClb, no del(17p) VenG vs. GClb in dependence of del(17p) N

  8. Slide 8: Acquired del(17p) after treatment with GClb but not VenG

    Acquired del(17p) after treatment with GClb but not VenG % at baseline GCLB_Pat1 % at relapse 0 GCLB_Pat2 patients with decreasing del17p fraction VenG, no del(17p) GCLB_Pat3 GClb GCLB_Pat4 VenG- del(17p) GCLB_Pat5 3 patients with GCLB_Pat6 increasing del17p fraction GCLB_Pat7 GClb, no del(17p) 0% 2

  9. Slide 9: Del(11q): PFS and acquired aberrations after therapy

    Del(11q): PFS and acquired aberrations after therapy GCLB_Pat01 % at baseline GCLB_Pat02 GCLB_Pat03 % at relapse GCLB_Pat04 5 GCLB_Pat05 patients with GCLB_Pat06 VenG, no del(11q) GCLB_Pat07 decreasing del11q fraction GCLB_Pat08 GClb GCLB_Pat09 GCLB_Pat10 GCLB_Pat11 GCLB_Pat12 VenG- del(11q) GCLB_Pa

  10. Slide 10: TP53 mutations: PFS and VAF changes over time

    TP53 mutations: PFS and VAF changes over time >10% VAF decrease >10% VAF increase stable VAF (<10% change) GClb VenG TP53wt, VenG 1 1 TP53mut, VenG 0.5 0.5 TP53wt, GClb TP53mut, GClb 0 0 decrease stable increase decrease stable increase Patients at risk VenG - TP53mut 0 2 4 6 8 10 12 14 16 18 20 22

  11. Slide 11: TP53 major mutations without del(17p) and TP53minor mutation do not have an impact on PFS

    TP53 major mutations without del(17p) and TP53minor mutation do not have an impact on PFS PFS: TP53 and del(17p) PFS: TP53 major and minor mutations 1.0 TP53minor (n=11) 0.8 TP53wt, no del(17p) TP53wt (n=368) Cum Survival 0.6 TP53mut, no del(17p) TP53major (n=43) 0.4 TP53mut, del(17p) 87% 0.2 88% TP

  12. Slide 12: BIRC3 mutations: PFS and VAF changes over time

    BIRC3 mutations: PFS and VAF changes over time >10% VAF decrease >10% VAF increase stable VAF (<10% change) 1.0 PFS: BIRC3 GClb VenG 0.8 1 1 BIRC3wt, VenG Cum Survival 0.6 BIRC3mut, VenG 0.5 0.5 0.4 BIRC3wt, GClb 0.2 0 0 BIRC3mut, GClb decrease stable increase decrease stable Increase 0.0 0 12 24 36

  13. Slide 13: BIRC3 minor mutations associate with short PFS

    BIRC3 minor mutations associate with short PFS >10% VAF decrease >10% VAF increase stable VAF (<10% change) PFS: BIRC3 GClb VenG 1 1 BIRC3wt 0.5 0.5 BIRC3major 91% BIRC3minor 0 0 5% 4% decrease stable increase decrease stable Increase 0 4 8 12 16 20 24 28 32 36 n0 1 2 3 4 5 6 7 8 9 10 11 n BIRC3maj

  14. Slide 14: Minor mutations in SF3B1 and NOTCH1 and PFS

    Minor mutations in SF3B1 and NOTCH1 and PFS NOTCH1 SF3B1 SF3B1min SF3B1wt NOTCH1wt 73% NOTCH1maj 80% SF3B1maj 23% NOTCH1min 4% 5% 15% NOTCH1maj vs. NOTCH1wt: HR 1.67 (95%CI 1.21-2.30) SF3B1maj vs. SF3B1wt: HR 1.60 (95%CI 1.12-2.28) NOTCH1min vs. NOTCH1wt: HR 2.25 (95%CI 1.27-3.99) SF3B1min vs. SF3B1

  15. Slide 15: IGHV status, del(17p) and overall survival

    IGHV status, del(17p) and overall survival OS: del(17p) OS: IGHV mutation status GClb - IGHVmut VenG, no del(17p) VenG - IGHVmut GClb, no del(17p) VenG - IGHVunm GClb - IGHVunm VenG- del(17p) GClb, del(17p) VenG- IGHVunm VenG – del(17p) HR 3.52 (95%CI 1.53-8.17) VenG- IGHVmut HR 1.61 (95%CI 0.74-3.5

  16. Slide 16: SF3B1 and NOTCH1 mutation status and overall survival

    SF3B1 and NOTCH1 mutation status and overall survival OS: SF3B1 OS: NOTCH1 VenG- SF3B1mut VenG – NOTCH1unm VenG – SF3B1unm GClb, SF3B1unm VenG- NOTCH1mut GClb, NOTCH1unm GClb, NOTCH1mut GClb, SF3B1mut VenG – SF3B1mut VenG – NOTCH1mut HR 0.76 (95%CI 0.23-2.49) HR 1.51 (95%CI 0.70-3.26) VenG – SF3B1un

  17. Slide 17: Multivariate analysis and PFS for GClb and VenG

    Multivariate analysis and PFS for GClb and VenG PFS HR 95%CI p VenG treatment 0.24 0.17-0.34 <0.001 IGHV unmutated 2.51 1.77-3.58 <0.001 del(17p) 1.98 1.20-3.29 0.008 CKT 1.92 1.28-2.87 0.002 TLS risk category high 1.53 1.08-2.16 0.016 OS HR 95%CI p del(17p) 4.58 2.59-8.15 <0.001 Serum β2mg > 3.5 2.

  18. Slide 18: Acquired mutations after VenG and GClb treatment

    Acquired mutations after VenG and GClb treatment VenG GClb n=25 n=88 (number of analysed patients) 2 1 0 0 1 2 3 4 5 6 newly mutated patients ATM BIRC3 BRAF EGR2 FBXW7 No acquired mutations in POT1 BCL2, BIM, BAX, RPS15 BCL-XL or MCL1 SF3B1 detected TP53 VenG GClb

  19. Slide 19: Summary

    Summary At a median follow up of 52 months VenG is superior to GClb independent of IGHV and del(17p) status. Del(17p) and unmutated IGHV remain prognostic factors for PFS. TP53 mutations, minor or major, have no impact on PFS in absence of del(17p) in CLL14. Mutated BIRC3 and del(11q) is prognostic

  20. Slide 20: Acknowledgements

    ACKNOWLEDGEMENTS We thank all patients, their families and their physicians for trial participation and donation of samples. This work was supported by Hoffmann-La Roche and Abbvie.

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