Updates in Hematology Disclosure Received honoraria on Speaker s Bureau for Pfizer and Takeda Oncology Received honoraria for Advisory Board of Pfizer and Lilly Manpreet Chahal, PharmD, PhD Oncology Pharmacist, Summit Cancer Centers, Spokane WA Adjunct Clinical Instructor, WSU College of Pharmacy mschahal@wsu.edu Northwest Pharmacy ConvenJon June 3, 2016 Objectives Summarize medicajons approved for hematological indicajons and their mechanism of acjon IdenJfy appropriate pajents and clinical benefits of each medicajon Review common adverse effects and appropriate management strategies Our Setting Summit Cancer Centers OutpaJent Oncology Clinics Spokane WA Spokane Valley WA Post Falls ID Satellite Once-a-month clinics Colfax WA Colville WA St Maries ID 5 Medical Oncologists, 2 NPs Infusion Centers Specialty MedicaJon Dispensing RadiaJon Clinical Trials (Phase II-IV) Darzalex (daratumumab) Relapsed/Refractory MulJple Myeloma AnJ-CD38 monoclonal anjbody CD38 highly expressed on myeloma cells 16 mg/kg IV weekly for weeks 1-8, every 2 weeks for weeks 9-24 and monthly thereaber unjl disease progression Pre-medicate with steroid, anjhistamine & anjpyrejc 1 hr prior to all infusions Post-infusion medicate with oral steroids on days 1 & 2 for delayed reacjons 100 mg/5 ml and 400 mg/20 ml vials in solujon 1
Darzalex (daratumumab) Clinical Trial InformaJon Open-label, single arm monotherapy Most pajents highly pre-treated Primary outcome was overall response rate Table 5: Efficacy results for Study 1 Overall response rate (ORR) 95% CI (%) N=106 31 (29.2%) (20.8, 38.9) Stringent complete response (scr) 3 (2.8%) Complete response (CR) 0 Very good partial response (VGPR) 10 (9.4%) Partial response (PR) 18 (17.0%) ORR = scr+cr+vgpr+pr CI = confidence interval Darzalex (daratumumab) Infusion reacjons (pre & post medicajon needed) Herpes zoster reacjvajon (prophylaxis recommended) Drug-Lab InteracJon Interferes with cross-matching of RBCs, cross-match prior to start FaJgue, back pain, pyrexia, cough, nausea & URIs Empliciti (elotuzumab) Empliciti (elotuzumab) - MOA Relapsed/Refractory MulJple Myeloma, in combinajon with lenalidomide and dexamethasone AnJ-SLAMF7 (CS1) anjbody SLAMF7 expressed on myeloma and NK cells 10 mg/kg IV weekly x 2weeks, then q2weeks thereaber (Jtrate per PI) Pre-medicate with IV steroid, anjhistamine, H2 blocker & anjpyrejc 300 mg & 400 mg single dose vials Empliciti (elotuzumab) Randomized, open-label trial Lenalidomide & dexamethasone +/- elotuzumab Table 7: Efficacy Results EMPLICITI + Lenalidomide/ N=321 Lenalidomide/ N=325 PFS Hazard Ratio [95% CI] 0.70 [0.57, 0.85] Stratified log-rank test p-value* 0.0004 Median PFS in months [95% CI] 19.4 [16.6, 22.2] 14.9 [12.1, 17.2] Response Overall Response (ORR) n (%) 252 (78.5) 213 (65.5) [95% CI] [73.6, 82.9] [60.1, 70.7] p-value 0.0002 Complete Response 14 (4.4) 24 (7.4) (CR + scr), n (%) Very Good Partial Response 91 (28.3) 67 (20.6) (VGPR) n (%) Partial Response (PR) n (%) 147 (45.8) 122 (37.5) Empliciti (elotuzumab) Second primary malignancies Infusion reacjons InfecJon Hepatotoxcicity FaJgue, diarrhea, fever, cough, peripheral neuropathy, nasopharyngijs and pneumonia 2
Ninlaro (ixazomib) Relapsed/Refractory MulJple Myeloma, in combinajon with lenalidomide and dexamethasone Proteosome inhibitor 4 mg orally days 1, 8 and 15 of each 28 day cycle 4 mg, 3 mg and 2.3 mg capsules Ninlaro (ixazomib) - MOA Ninlaro (ixazomib) Randomized, double-blind, placebo controlled trail Ixazomib OR placebo + lenalidomide and dexamethasone Table 7: Progression-Free Survival and Response Rate NINLARO + Lenalidomide and (N = 360) Placebo + Lenalidomide and (N = 362) Progression-free Survival PFS Events, n (%) 129 (36) 157 (43) Median (months) 20.6 (17.0, NE) 14.7 (12.9, 17.6) Hazard Ratio * 0.74 (0.59, 0.94) p-value 0.012 Response Rate Overall Response Rate, n (%) 282 (78) 259 (72) Complete Response 42 (12) 24 (7) Very Good Partial Response 131 (36) 117 (32) Partial Response 109 (30) 118 (33) NE: Not evaluable. Ninlaro (ixazomib) Peripheral neuropathy Hepatotoxcicity Embryo-fetal toxicity N/V/D, rash, fluid retenjon, thrombocytopenia Imbruvica (ibrutinib) Chronic lymphocyjc leukemia (CLL), 1 st line Bruton tyrosine kinase (btk) inhibitor 420 mg po once daily 140 mg capsules Imbruvica (ibrutinib) - MOA 3
Imbruvica (ibrutinib) Randomized, muljcenter, double-blind, placebo controlled trail IbruJnib OR placebo in combinajon with bendamusjne & rituximab Endpoint Progression Free Survival a Table 15: Efficacy Results in Study 4 IMBRUVICA + BR N=289 Placebo + BR N=289 Number of events (%) 56 (19.4) 183 (63.3) Median, months Not reached 13.3 (11.3, 13.9) HR 0.20 (0.15, 0.28) Overall Response Rate a 82.7% 67.8% a IRC evaluated, Twenty four subjects (8.3%) in the IMBRUVICA + BR arm and six subjects (2.1%) in the placebo + BR arm Imbruvica (ibrutinib) Hemorrhage InfecJons Cytopenias Afib HTN TLS Neutropenia, thrombocytopenia, diarrhea, anemia, rash Venclexta (venetoclax) Chronic lymphocyjc leukemia (CLL) with 17p delejon, 2 nd line therapy BCL-2 inhibitor 20 mg daily for 7 days, Jtrate up to 400 mg po daily per PI Tablets 10 mg, 50 mg, 100 mg Venclexta (venetoclax) - MOA Venclexta (venetoclax) Open-label, single arm, muljcenter clinical trial PaJents with CLL with confirmed 17p delejon and post 1 line of therapy Table 10. Efficacy Results for Patients with Previously Treated CLL with 17p Deletion by IRC VENCLEXTA N=106 ORR, n (%) CR + CRi, n (%) CR, n (%) CRi, n (%) 85 (80.2) (71.3, 87.3) 8 (7.5) 6 (5.7) 2 (1.9) npr, n (%) 3 (2.8) PR, n (%) 74 (69.8) CI = confidence interval; CR = complete remission; CRi = complete Venclexta (venetoclax) ContraindicaJons Concomitant use with strong CYP3A inhibitors TLS Assess risk and pre-medicate pajents, ensure adequate hydrajon Neutropenia Embryo-Fetal toxicity Neutropenia, diarrhea, nausea, anemia, UTI, thrombocytopenia and fajgue ImmunizaJon do not administer live alenuated vaccines prior to, during or aber venetoclax treatment 4
Opdivo (nivolumab) Opdivo (nivolumab) - MOA Relapsed Classical hodgkin lymphoma post HSCT and post transplant Adcetris treatment AnJ-PD1 anjbody, immunotherapy 3 mg/kg IV every 2 weeks 40 mg/4 ml single-dose vial & 100 mg/10 ml single-dose vial Opdivo (nivolumab) Single-arm, open-label, muljcenter trial Table 19: Efficacy in chl after Autologous HSCT and Brentuximab Vedotin Objective Response Rate, n (%) a Complete Remission Rate Partial Remission Rate Median Duration of Response (months) Range Median Time to Response (months) Range a Per 2007 revised International Working Group criteria. Trial 8 and Trial 9 (n=95) 62 (65%) (55, 75) 7 (7%) (3, 15) 55 (58%) (47, 68) 8.7 (6.8, NE) 0.0+, 23.1+ 2.1 0.7, 5.7 Opdivo (nivolumab) PneumoniJs ColiJs HepaJJs NephriJs Infusion reacjon FaJgue, rash, pruritus, diarrhea and nausea Which of the following therapeujc agents interferes with crossmatching of RBCs? A. Elotuzumab B. Daratumumab C. IbruJnib D. Nivolumab 5
PaJents should avoid live alenuated vaccines prior to, during and aber treatment with which of the following therapeujc agent? A. Elotuzumab B. Daratumumab C. Venetoclax D. Nivolumab PneumoniJs is a severe adverse effect of the following agent: A. Elotuzumab B. Daratumumab C. IbruJnib D. Nivolumab References Darzalex (daratumumab). Prescribing InformaJon. November 2015. Janssen Biotech, Inc. EmpliciJ (elotuzumab). Prescribing InformaJon. November 2015. Bristol-Myers Squibb Company. Ninlaro (ixazomib). Prescribing InformaJon. November 2015. Takeda PharmaceuJcal Company. Imbruvica (ibrujnib). Prescribing InformaJon. May 2016. Jansen Biotech, Inc. Venclexta (venetoclax). Prescribing InformaJon. April 2016. AbbVie, Inc. Opdivo (nivolumab). Prescribing InformaJon. May 2016, Bristol- Myers Squibb Company. Questions??? mschahal@wsu.edu Go Cougs!! 6