New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida Brentuximab Vedotin + ESHAP in R/R Classical Hodgkin’s Lymphoma *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This program is supported by educational grants from Amgen, Celgene Corporation, Merck, Incyte, Seattle Genetics, and Takeda Oncology.

Brentuximab Vedotin + ESHAP for R/R cHL: Background 1. Graf SA, et al. ASH Education Book. 2014: Sureda A, et al. Ann Oncol. 2005;16: Majhail NS, et al. Biol Blood Marrow Transplant. 2006;12: Moskowitz CH, et al. Blood. 2012;119: Kuruvilla J, et al. Blood. 2011;117: Slide credit: clinicaloptions.comclinicaloptions.com  20% to 30% of pts with cHL relapse following or are refractory to upfront chemotherapy [1]  SOC for R/R cHL after frontline therapy is salvage therapy followed by ASCT [2,3] –Pts who achieve CR on salvage therapy are more likely to have better outcomes [4]  Standard salvage chemotherapy regimens associated with toxicity and variable CR rates (19% to 60%) [5]  Induction therapy prior to transplantation in R/R cHL ‒ CR rates vary considerably depending on regimen

Brentuximab Vedotin + ESHAP for R/R cHL: Transplantation-Eligible Pts  Brentuximab vedotin: anti-CD30 antibody–drug conjugate –Induces cell death by inhibiting mitotic spindle [1]  Approved for –cHL that has failed ASCT or, if transplantation ineligible, after failure of 2 or more multiagent chemotherapy regimens –sALCL after failure of 1 or more multiagent chemotherapy regimens  Current study evaluated the role of brentuximab vedotin + ESHAP (BRESHAP) in transplantation-eligible pts with R/R cHL [2] 1. Younes A, et al. Hematol Oncol Clin North Am. 2014;28: Garcia-Sanz R, et al. ASH Abstract 582. Slide credit: clinicaloptions.comclinicaloptions.com

Brentuximab Vedotin + ESHAP for R/R cHL: Phase I/II Open-Label Study  Autologous PBSC collection before cycles 2, 3 of ESHAP; CD34+ quantification: ≥ x 106/kg CD34+ cells  Neutropenia prophylaxis: mandatory G-CSF from Day +7, peg-filgrastim recommended  Phase II: up to 66 pts  Primary objectives: phase I, MTD; phase II, ORR/CR after BRESHAP salvage therapy before ASCT  Secondary objectives: toxicity and stem cell mobilization capacity after BRESHAP; and TRM, TTF, PFS, and OS after BRESHAP, chemotherapy, ASCT, and brentuximab vedotin Slide credit: clinicaloptions.comclinicaloptions.com Garcia-Sanz R, et al. ASH Abstract 582. Relapsed or refractory cHL (N = 66) BRESHAP ESHAP* Q21-28 Days x 3 Brentuximab Vedotin 0.9, 1.2, or 1.8 mg/kg Day 1 each cycle and 21 days post 3rd ESHAP (n = 9-18) ASCT/BEAM Brentuximab post-ASCT From Day +28 to doses, every 21 days ± Radiotherapy *ESHAP: etoposide 40 mg/m 2, 2-hr infusion Days 1-4; methylprednisone 200 mg/day Days 1-4; cytarabine 2 g/m 2, 2-hr infusion, 1 dose Day 5; cisplatin 25 mg/m 2, continuous infusion Days 1-4; G-CSF support.

Brentuximab Vedotin + ESHAP for R/R cHL: Phase I Response and Safety  All 9 pts had CR by CT pre- and posttransplantation and were PET negative pre-and posttransplantation –Exception: 1 pt was PET positive before but PET negative after transplantation  No DLT identified  Brentuximab vedotin MTD: 1.8 mg/kg every 21 days  Grade 4 hematologic toxicity: neutropenia (n = 2), thrombocytopenia (n = 1) Slide credit: clinicaloptions.comclinicaloptions.com Garcia-Sanz R, et al. ASH Abstract 582. Severe AEsWhenRelated toTime to Resolution, Days Nonneutropenic feverEnd of 1st cycleCytarabine3 Nonneutropenic feverPost-2nd cycleCatheter insertion1 PneumothoraxPre-2nd cycleCatheter insertion1 Febrile neutropeniaPost-1st cycleNeutropenia7

Brentuximab Vedotin + ESHAP for R/R cHL Lymphoma: Phase I + Phase II  N = 36  Median age: 33 yrs (range: 18-60)  Male/female: 20/16 –Primary refractory: 58% –Relapsed: 42% (6 early, 9 late)  145 courses of BRESHAP have been administered –Serious AEs (n = 19), febrile neutropenia (n = 9); all resolved –No deaths, 1 discontinuation due to PD  Stem cell collection (n = 24); no mobilization failures  Evaluable for pre-ASCT response (n = 24) –ORR: 96%; CR: 83% Slide credit: clinicaloptions.comclinicaloptions.com Garcia-Sanz R, et al. ASH Abstract 582.

Brentuximab Vedotin + ESHAP for R/R cHL: Phase I/II Toxicity Slide credit: clinicaloptions.comclinicaloptions.com Garcia-Sanz R, et al. ASH Abstract 582. AE, %Grade 1234 Nonhematologic Pain19600 Emesis14600 Asthenia11630 Constipation11000 Mucositis81180 Hyporexia8600 Renal dysfunction6300 CMV reactivation0300 Hematologic Neutropenia Anemia Thrombocytopenia

Brentuximab Vedotin + ESHAP for R/R cHL: Conclusions  BRESHAP appears well tolerated in pts with R/R cHL who are eligible for high-dose therapy and ASCT –No stem cell mobilization failures were reported  Promising pre-ASCT response after BRESHAP –ORR: 96% –Metabolic CR: 83%  Recommended dose for brentuximab vedotin when combined with ESHAP is the same dose as in the label: 1.8 mg/kg every 21 days Slide credit: clinicaloptions.comclinicaloptions.com Garcia-Sanz R, et al. ASH Abstract 582.

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