POLATUZUMAN EN LINFOMA NO HODGKIN.1.2DR ZETINA.pptx

POLATUZUMAB EN LINFOMAS NO HODGKIN TRIPLE HIT

1. PRESENTATION OF CLINICAL CASES POLATUZUMAB DR.LUIS MIGUEL ZETINA-TOACHE CANCER CONSULTANTS GUATEMALA ONCOSALUD PERSONALIZADA GT DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) (FIRST LINE AND RELAPSE)

2. ESPECTRO DE LAS Rearranged Ig genes ( IgH , IgK , IgL )

3. ) Post transplant lymphomas Classic Hodgkin’s LymphomA Follicular lymphoma Burkitt’s lymphoma DLBCL (GC Type) Lymphocyte Predominant Hodgkin’s lymphoma

4. MONOMETHYL AURISTATINA VEDOTINA

5. CLINICAL CASE

6. STAGING: WHOLE BODY FDG 18 PET/CT

7. STAGING: WHOLE BODY FDG 18 PET/CT

8. Hipermetabolic lytic lesion of right sacrum , with infiltration of neuroforamina , spinal canal, pre- V vertebral space , right piriformis muscle and gluteus m maximus muscle . SUV15.5. Prevertebral ganglia of 1.5 cm SUV 9.3 Lytic lesión in the left femoral head and neck SUV 6.5

9. MATURE B-CELL LYMPHOMA CONSISTENT WITH GERMINAL CENTER DLBCL

10. CLINICAL CASE: DLBCL TREATMENT: R-CHOP VRS POLARIX ?

11. APRIL 2023 POLARIX JUNIO 2019 GO29365

12. POLARIX: Study Design Multicenter, double-blind, placebo-controlled phase III trial Primary endpoint: investigator-assessed PFS Secondary endpoints: EFS, CRR at end of treatment, DFS, OS, safety Slide credit: clinicaloptions.com Tilly. ASH 2021. Abstr LBA1. Tilly. NEJM. 2021;[Epub] Patients aged 18-80 yr with previously untreated DLBCL, IPI 2-5, ECOG PS 0-2 (N = 879) Cycles 7 and 8 Polatuzumab Vedotin 1.8 mg/kg + R-CHP + Vincristine placebo (n = 440) R-CHOP + Polatuzumab Vedotin placebo (n = 439) Stratification by IPI score (2 vs 3-5); bulky disease (<7.5 vs ≥7.5 cm); and geographic region (Western Europe, US, Canada and Australia vs Asia vs rest of world) Rituximab 375 mg/m 2 Cycles 1-6 (21-day cycles) R-CHOP: IV rituximab 375 mg/m 2 , cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², and vincristine 1.4 mg/m² administered on Day 1 + oral prednisone 100 mg QD Days 1-5. 

13. POLARIX: Polatuzumab Vedotin + R-CHP vs R-CHOP PFS and EFS PFS (Primary Endpoint) EFS Slide credit: clinicaloptions.com Tilly. ASH 2021. Abstr LBA1. Tilly. NEJM. 2021;[Epub] Median follow-up: 28.2 mo 24-mo PFS: 76.7% polatuzumab vedotin + R-CHP vs 70.2% R-CHOP PFS (%) EFS (%) Mo Mo Pola-R-CHP R-CHOP 440 404 353 327 246 78 NE NE 439 389 330 296 220 78 3 NE HR: 0.75 (95% CI: 0.58-0.96; P = .02) Patients at Risk, n Pola-R-CHP R-CHOP HR: 0.73 (95% CI: 0.57-0.95; P = .02) 440 402 348 323 243 78 NE NE 439 386 327 294 218 78 3 NE 100 80 60 40 20 6 12 18 24 30 36 42 Pola-R-CHP R-CHOP 100 80 60 40 20 6 12 18 24 30 36 42 Patients at Risk, n Pola-R-CHP R-CHOP

14. CLINICAL CASE: DLBCL TREATMENT OPTIONS: R-CHOP VRS POLARIX ?

15. Use of Polatuzumab / Bendamustine in Relapse DLBCL Previous experience in our center

16. APRIL 2023 POLARIX JUNIO 2019 GO29365

17. Approval of polatuzumab vedotin in R/R DLBCL is based on GO29365 results 1,2 *Patients with Grade >1 PN were excluded; † 6–8 weeks after completion of study treatment. BCR, best complete response; BOR, best overall response; BR, bendamustine + rituximab; CR, complete response; DLBCL, diffuse large B-cell lymphoma; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; IRC, Independent review committee; OS, overall survival; PET/CT, positron emission tomography/computed tomography; PFS, progression-free survival; PN, peripheral neuropathy; Pola, polatuzumab vedotin; PRA, primary response assessment; R, randomized; R/R, relapsed/refractory. 1. Polivy Summary of Product Characteristics. Available at: www.ema.europa.eu/polivy-epar-medicine-overview_en.pdf . [Accessed October 17, 2022]; 2. Sehn LH, et al. J Clin Oncol 2020;38:155–65; 3. Sehn LH, et al. Blood Adv 2022;6:533–43. Primary endpoint: IRC-assessed CR at PRA † measured by PET/CT Secondary endpoints: BOR, BCR, DOR, IRC-assessed PFS, OS, and safety In GO29365 the primary endpoint was met, with an IRC‐assessed CR rate of 40.0% with Pola+BR versus 17.5% with BR 2 An extension cohort including patients who received Pola+BR was later enrolled, resulting in a CR rate of 38.7% 3 We report final results from the GO29365 study with extended follow-up of up to 5 years, including updated results from the Phase lb safety run-in, Phase ll randomized, and extension cohorts R 1:1 BR (n=40) Pola+BR (n=40) Pola+BR (n=6) Pola+BR (n=106) Patients* R/R DLBCL Age ≥18 years old Stem cell transplant ineligible ECOG PS 0–2 Received ≥1 prior line of therapy Safety run-in cohort (Phase Ib ) Extension cohort (Phase II) Randomized cohort (Phase II)

18. Polatuzumab Vedotin + BR vs BR for R/R DLBCL Polatuzumab vedotin: antibody – drug conjugate targeting CD79b with a toxic payload (MMAE) Patients with histologically confirmed R/R DLBCL; received ≥1 prior tx; ECOG PS 0-2; ineligible for SCT; no grade IIIb FL; no transformed DLBCL; no CNS lymphoma; no prior allo HSCT; no auto HSCT within 100 days (N = 80) Polatuzumab Vedotin 1.8 mg/kg, D1 of each cycle + Bendamustine 90 mg/m 2 on D1,3 (C1), then D1,2 (each cycle) + Rituximab 375 mg/m 2 , D1 (each cycle) (n = 40) Bendamustine 90 mg/m 2 on D1,3 (C1), then D1,2 (each cycle) + Rituximab 375 mg/m 2 , D1 (each cycle) (n = 40) Primary endpoints: CR rate (PET/CT) Key secondary endpoints: ORR at EOT, DoR, PFS Stratified by DoR to last tx (≤12 vs >12 mo) Sehn. JCO. 2020;38:155. ≤6 21-day cycles Phase II trial

19. Improved PFS and OS with Pola+BR persisted with extended follow up HR, hazard ratio. No. of patients at risk Pola+BR 40 36 33 30 25 22 19 16 16 15 12 11 11 11 11 10 10 9 9 9 9 9 8 8 7 7 7 7 7 7 5 4 4 1 BR 40 28 17 11 10 7 7 7 6 6 5 5 5 4 3 3 3 2 2 2 2 2 2 2 2 2 2 2 2 2 1 No. of patients at risk Pola+BR 40 32 28 25 20 18 16 13 12 10 9 9 9 9 9 6 6 5 5 5 5 5 4 4 4 4 4 4 4 4 2 1 1 BR 40 24 13 6 6 6 5 5 4 4 4 2 2 1 Randomized cohort Median duration of follow-up for patients treated with Pola+BR was 59.9 months Time (months) OS (probability) 1.0 0.8 0.6 0.4 0.2 4 8 28 68 64 60 56 52 48 44 40 36 32 24 20 16 12 Pola+BR BR Censored Median OS, months (95% CI) Pola+BR (n=40): 12.4 (9.0–32.0) BR (n=40): 4.5 (3.7–6.0) HR: 0.4; 95% CI: 0.2–0.7 No. of patients at risk Pola+BR 40 36 33 30 25 22 19 16 16 15 12 11 11 11 11 10 10 9 9 9 9 9 8 8 7 7 7 7 7 7 5 4 4 1 BR 40 28 17 11 10 7 7 7 6 6 5 5 5 4 3 3 3 2 2 2 2 2 2 2 2 2 2 2 2 2 1 Pola+BR BR Censored Median PFS, months (95% CI) Pola+BR (n=40): 9.2 (6.0–13.9) BR (n=40): 3.7 (2.1–4.5) HR: 0.4; 95% CI: 0.2–0.7 PFS (probability) 1.0 0.8 0.6 0.4 0.2 4 60 48 28 16 12 8 64 56 52 44 40 36 32 24 20 Time (months) No. of patients at risk Pola+BR 40 32 28 25 20 18 16 13 12 10 9 9 9 9 9 6 6 5 5 5 5 5 4 4 4 4 4 4 4 4 2 1 1 BR 40 24 13 6 6 6 5 5 4 4 4 2 2 1 No. of patients at risk Pola+BR 106 82 69 53 45 37 32 29 25 20 19 18 15 14 12 4 3 3 2 2 1 106 93 83 68 58 51 48 45 40 37 37 36 34 32 29 12 8 8 6 5 4 2 Extension cohort Median duration of follow-up for was 29.2 months Pola+BR Censored Median PFS, months (95% CI) Pola+BR (n=106): 7.0 (5.1–9.8) PFS (probability) 1.0 0.8 0.6 0.4 0.2 Time (months) No. of patients at risk 2 4 14 42 38 32 28 26 24 22 20 18 16 12 10 8 6 40 36 34 30 Pola+BR 106 82 69 53 45 37 32 29 25 20 19 18 15 14 12 4 3 3 2 2 1 Time (months) OS (probability) 1.0 0.8 0.6 0.4 0.2 Pola+BR Censored Median OS, months (95% CI) Pola+BR (n=106): 12.3 (8.3–17.0) No. of patients at risk 2 4 14 44 40 34 30 26 24 22 20 18 16 12 10 8 6 42 38 36 32 28 Pola+BR 106 93 83 68 58 51 48 45 40 37 37 36 34 32 29 12 8 8 6 5 4 2

20. Relapse RCHOP Pola/ Benda

21. Relapse Pola/ Benda

22. Linfoma No Hodgkin Tipo Folicular.