New Drugs Update: Targeted Therapies

Transcription

1 NEW DRUG UPDATES

2 New Drugs Update: Targeted Therapies Megan Derba, Pharm.D. Supervising Pharmacist Hematology/Oncology Lafayette Family Cancer Institute Brewer, Maine November 2, 2018

3 Introduction Disclosures I have no conflicts of interest to disclose. Learning Objective Summarize the safety and efficacy data for recently approved targeted therapies. Presentation Outline Breast Cancer Chronic Lymphocytic Leukemia NSCLC

4 Learning Assessment Select all that apply: Abemaciclib is to be used: A) Alone with no other agents B) In combination with fulvestrant C) In combination with an aromatase inhibitor D) After progression on palbociclib

5 New Targeted Therapy Agents/Indications Breast Talazoparib Neratinib Ribociclib Abemaciclib Hepatocellular Lenvatinib NSCLC Dacomitinib Osimertinib Afatinib Alectinib Ceritinib Brigatinib Ovarian Rucaparib Olaparib CLL Duvelisib Venetoclax Acalabrutinib Melanoma Encorafenib + binimetinib Dabrafenib + trametinib

6 Updates in Breast Cancer

7 Spring L, Bardia A, Modi S. Targeting the cyclin D-cyclin-dependent kinase (CDK) 4/6-retinoblastoma pathway with selective CDK 4/6 inhibitors in hormone receptor-positive breast cancer: rationale, current status, and future directions. Discov Med. 2016;21(113):65-74.

8 CDK 4/6 Inhibitors Palbociclib (Ibrance TM ) First line + aromatase inhibitor (post-menopausal) Second line + fulvestrant Ribociclib (Kisqali TM ) First line + aromatase inhibitor (pre- and post-menopausal) First or second line + fulvestrant Abemaciclib (Verzenio TM ) First line + aromatase inhibitor (post-menopausal) Second line + fulvestrant Monotherapy, following endocrine therapy AND prior chemotherapy in metastatic setting

9 Palbociclib Ribociclib Abemaciclib Dosing Daily x21 days, 7 days off Daily x21 days, 7 days off Twice Daily Adverse Effects Neutropenia, nausea, fatigue QT prolongation, increased LFTs, neutropenia Diarrhea, neutropenia, increased LFTs, increase in VTE risk DDIs CYP3A4 CYP3A4, tamoxifen CYP3A4 Unique First, well tolerated Pre-menopausal Monotherapy

10 Neratinib (Nerlynx TM ) Kinase inhibitor for early stage HER2 breast cancer, to follow adjuvant trastuzumab therapy Dose: 240 mg daily x 1 year (6 x 40 mg tablets) Side Effects: Diarrhea: Prophylactic anti-diarrheal therapy starting with first dose of neratinib Reported in nearly 95% of patients Hepatotoxicity: Monitor LFTs at least every 3 months

11 Talazoparib (Talzenna TM ) Approved October 16, 2018 gbrca mutation, HER2-negative Dual acting PARP inhibitor inhibits PARP enzyme and traps PARP enzyme on single-strand breaks Patients must be selected for therapy based on FDAapproved companion diagnostic Dose: 1 mg daily DDIs: Reduce dose when administered with P-gp inhibitors Side effects: neutropenia, fatigue, nausea Severe adverse events: myelodysplastic syndrome

12 Updates in Relapsed or Refractory CLL BTK inhibitors PI3K inhibitors BCL-2 inhibitor

13 Duvelisib (Copiktra TM ) Phosphoinositide 3-kinase (PI3K inhibitor) with activity against multiple isoforms Indication: Relapsed or refractory CLL and FL after 2 prior therapies Dose: 25 mg twice daily Side effects: diarrhea, neutropenia, rash, fatigue, nausea, infection Severe adverse events: infections, colitis, cutaneous reactions, pneumonitis Antibiotic prophylaxis recommended PJP and CMV

14 Venetoclax (Venclexta TM ) B-cell lymphoma 2 (BCL-2) inhibitor Indication: CLL with or without 17p deletion, after at least one prior therapy Can be given with or without rituximab Dose: Target dose is 400 mg daily Starting dose is 20 mg, titrated up weekly to target dose DDIs: CYP3A4 Venetoclax is P-gp substrate and inhibitor Side effects: neutropenia, fatigue, headache, infection Serious adverse events: tumor lysis syndrome Consider inpatient stay for first dose Prophylactic allopurinol

15 Acalabrutinib (Calquence TM ) Second-generation bruton tyrosine kinase (BTK) inhibitor Indication: mantle cell lymphoma with at least one prior therapy Dose: 100 mg twice daily DDIs: CYP3A4, avoid PPIs, stagger doses with H2- receptor agonists Side effects: headache, diarrhea, fatigue, nausea, weight increase Severe adverse events: atrial fibrillation, bleeding events Similar to ibrutinib, fewer reported side effects

16 Updates in NSCLC

17 Dacomitinib (Vizimpro TM ) Kinase inhibitor Indication: first line treatment with EGFR exon 19 deletion or exon 21 L858R substitution mutation in NSCLC Dose: 45 mg daily DDIs: Avoid PPIs, separate H2-receptor antagonist, CYP2D6 Side effects: diarrhea, rash, decreased appetite, cough Severe adverse events: Interstitial lung disease, diarrhea, rash

18 Osimertinib (Tagrisso TM ) Kinase inhibitor Indication: first line treatment with EGFR exon 19 deletion or exon 21 L858R substitution mutation in NSCLC and second line therapy in patients with EGFR T790M mutation Dose: 80 mg daily DDIs: CYP3A4 Side effects: diarrhea, rash, decreased appetite, stomatitis Severe adverse events: Interstitial lung disease, QTc prolongation, cardiomyopathy, keratitis

19 Learning Assessment Select all that apply: Abemaciclib is to be used: A) Alone with no other agents B) In combination with fulvestrant C) In combination with an aromatase inhibitor D) After progression on palbociclib

20 Advances in Leukemia Therapeutics Robert Cade, PharmD BCOP Department of Pharmacy Services University of Vermont Medical Center

21 Disclosures As an accredited provider of continuing education, the Northern New England Clinical Oncology Society must ensure balance, independence, objectivity, and scientific rigor in all its educational activities. Any individual who is in a position to control content is required to disclose any financial relationship with commercial interests. Robert Cade has no relationships to disclose.

22 Learning objective Select an appropriate novel antineoplastic for the treatment of AML, given patient and diseasespecific factors

23 Learning assessment question DD is a 65 year old female patient. Her PMH is notable for mantle cell lymphoma diagnosed in She has received a number of lines of chemotherapy, including bendamustine, rituximab, lenalidomide, lomustine, etoposide, cytarabine, melphalan, and ibrutinib. She has been in remission from her mantle cell lymphoma for about 2 years. Now she has been newly diagnosed with AML with myelodysplastic related changes. It has complex cytogenetics, including del(5q) and 7, with a loss offunction mutation in TP57. She is otherwise in good health, with a good performance status, and wants curative treatment. Among currently FDAapproved therapies, which option is most likely to achieve this goal: A. Gemtuzumab ozogamicin (Mylotarg) B. Daunorubicin cytarabine liposome (Vyxeos) C. Enasidenib (Idhifa) D. Induction chemotherapy with the 7+3 regimen, consolidation with CAR T cell therapy E. Induction chemotherapy with the 7+3 regimen, followed by midostaurin (Rydapt)

24 Acute myeloid leukemia Most common acute leukemia in adults 19,520 estimated to be diagnosed in ,670 estimated deaths in 2018 Median age at diagnosis is 66 Increased incidence in Males European ethnicity Siegel RL, et al. Ca Cancer J Clin 2018; 68:7 30.

25 Diagnosis Therapy Induction Consolidation High dose cytarabine Allogeneic stem cell transplant Cure Reinduction CLAG±M FLAG IDA MEC High dose cytarabine Palliation Azacitidine Decitabine Low dose subcutaneous cytarabine Best supportive care

26 What is FLT3? FMS like tyrosine kinase 3 Important transmembrane signaling protein involved in hematopoiesis regulation FLT3 ligand Downstream signal molecule phosphorylation Cell division Normal FLT3 function

27 Two forms of activating FLT3 mutations No FLT3 ligand present FLT3 ITD No FLT3 ligand present FLT3 TKD Downstream signal molecule phosphorylation Cell division Internal tandem duplication Poor prognostic feature Downstream signal molecule phosphorylation Cell division Tyrosine kinase domain Prognostic impact controversial

28 Midostaurin Multi targeted tyrosine kinase inhibitor Activity against many proteins implicated in cancer Platelet derived growth factor receptor α and β Vascular endothelial growth factor receptor 1 (VEGFR 1) H RAS K RAS Multidrug resistant gene C kit FLT3 ITD and TKD Orally active Weisburg E et al. Canc Cell 2002; 1(5):

29 Midostaurin Induction: 50 mg by mouth twice daily Days 8 21 of induction Starts the day after 7+3 ends Gives time for FLT3 mutation assay to be finalized Avoids interaction with chemotherapy Consolidation: 50 mg by mouth twice daily Days 8 21 of consolidation (off label) Maintenance: 50 mg by mouth twice daily Continuously for 12 x 28 day maintenance cycles (off label)

30 Midostaurin Adverse effects: Most adverse effects will be caused by the induction or consolidation therapy Anemia, thrombocytopenia, leukopenia Neutropenic fever Mucositis Alopecia Pulmonary toxicity Interstitial lung disease Pneumonitis Rare one case of each reported in an early proof of concept trial Mild moderate nausea give with antiemetic prophylaxis QTc prolongation Monitor EKGs if other QTc prolonging drugs cannot be avoided CYP3A4 substrate interacts with CYP3A4 inhibitors and inducers Stone RL, et al. Blood 2005; 105:54 60.

31 CALGB RATIFY trial 717 patients with newly diagnosed FLT3(+) AML (either FLT3 ITD or TKD) midostaurin placebo Up to 4 cycles of consolidation + midostaurin Up to 4 cycles of consolidation + placebo Up to 1 year of midostaurin maintenance Up to 1 year of placebo maintenance Patients in remission could undergo allogeneic stem cell transplant at any time

32 Economic toxicity Cost per 25mg tablet: $ Cost per day of therapy: ~$500 Cost per induction and consolidation cycle: ~$7000 Cost per month during maintenance phase: ~$14,000 Total cost of treatment: $203,000

33 Therapy Induction Consolidation Diagnosis midostaurin Reinduction CLAG±M FLAG IDA MEC High dose cytarabine High dose cytarabine Allogeneic stem cell transplant High dose cytarabine + midostaurin Cure Palliation Azacitidine Decitabine Low dose subcutaneous cytarabine Best supportive care

34 Secondary AML AML caused by previous treatment (chemo or radiation) OR AML evolving from myelodysplastic syndrome AML with myelodysplastic related changes Poor prognosis Median survival: 6 months Allogeneic stem cell transplant recommended, if patient can be kept in remission Remission rates with standard chemotherapy: ~25 30% Bhatioa S. Semin Oncol 2013; 40:

35 Daunorubicin-cytarabine liposome Often known as CPX 351 Precise 1:5 molar ratio of daunorubicin to cytarabine Attempt to optimize exposure of each Based on maximum synergy in vitro Packed inside lipid double bilayer Preferentially taken up by marrow Increased plasma halflife Detectable 2 weeks after treatment Brilliant purple color Lancet JE, et al. Blood 2014; 123:

36 Daunorubicin-cytarabine liposome 44 mg daunorubicin = 100 mg cytarabine Induction: 44mg/m2 on Days 1, 3, and 5 Reinduction: 44mg/m2 on Days 1 & 3 Consolidation: 29mg/m2 on Days 1 & 3 Up to two cycles All doses given IV over 90 minutes

37 Adverse effects Prolonged anemia, thrombocytopenia, anemia Similar to 7+3 Mucositis Alopecia Moderate nausea/vomiting Febrile neutropenia Cardiomyopathy Tissue necrosis after extravasation Sepsis Invasive fungemia Pneumonia central line Anti infective prophylaxis

38 Adverse effects of particular interest Hemorrhage, including CNS hemorrhage Grade 3 4: 12% Fatal: 2% Neutropenia or thrombocytopenia prolonged more than 42 days following induction Death 30 day fatality rate: 6% 60 day fatality rate: 14% Causes: respiratory failure, infections, CNS hemorrhage

39 309 patients with newly diagnosed treatment related or myelodysplasticrelated AML Age Lancet, et al trial CPX 351 induction Up to 2 cycles of CPX 351 consolidation Up to 2 cycles of 5+2 consolidation 7+3 induction Financial toxicity Avg cost per dose: $15,500 Avg cost per induction cycle: $46,500 Avg cost per consolidation cycle: $31,000 Daunorubicin cytarabine 7+3 liposome (CPX 351) Overall survival 9.56 months 5.95 months Complete response 47.7% 33.3% 60 day mortality 13.7% 21.2% Grade 3 5 adverse effects 92% 91% Allogeneic transplant 34% 25% Allogeneic transplant at discretion of investigator Median survival after transplant Not reached months Lancet JE, et al. J Clin Oncol 2016; 34: (17suppl) abstr 7000.

40 Therapy Induction midostaurin CPX 351 Consolidation High dose cytarabine Allogeneic stem cell transplant High dose cytarabine + midostaurin Cure Diagnosis Reinduction CLAG±M FLAG IDA MEC High dose cytarabine CPX 351 consolidation Palliation Azacitidine Decitabine Low dose subcutaneous cytarabine Best supportive care

41 What is IDH mutation? Narayanese, et al. Licensed under the GNU Free Documentation License.

42 What is IDH mutation

43 IDH inhibitors Mutation Drug Dose IDH 1 Ivosidenib 500mg po daily IDH 2 Enasidenib 100mg po daily Approved for relapsed refractory AML with IDH mutations Orally active small molecule Reduces 2 hydroxyglutarate levels Decreases DNA and histone methylation Promotes normal myeloid differentiation of blasts Not cytotoxic May take up to six months before clinical response is seen

44 Adverse effects Generally mild Nausea, vomiting, diarrhea, decreased appetite No significant anemia, thrombocytopenia, or neutropenia Non infectious leukocytosis as blasts differentiate hydroxyurea QTc prolongation (ivosidenib) Blackbox warning: differentiation syndrome A large amount of myeloid blasts may get unstuck, differentiate, and leave the marrow in a short amount of time These may secrete large amounts of cytokines Cellular damage and inflammation result Potentially fatal Fathi AT, et al. JAMA Oncol 2018; doi: /jamaoncol [Epub ahead of print]

45 Differentiation sydrome Shortness of breath, fever, peripheral edema Patients should weigh themselves twice daily Any weight gain could be a sign of differentiation syndrome Radiography: Pulmonary infiltrates Pleural effusions Highly concerning Pericardial effusions New or increasing O2 need Increasing LFTs or SCr Fathi AT, et al. JAMA Oncol 2018; doi: /jamaoncol [Epub ahead of print]

46 Differentiation syndrome Patients should be thoroughly educated in signs and symptoms Present to ED if they occur, or if unexplained weight gain more than 2 kg Treatment: Admit patient Hold enasidenib Dexamethasone IV 10mg twice daily

47 AG221-C-001 trial Expansion cohort from phase I trial: 103 patients with relapsed refractory AML with IDH 2 mutation Enadesinib 100mg daily indefinitely Overall response rate Median time to response Median duration of response 38.5% 1.9 months 5.6 months Complete response 20.2% Stable disease for > 8 weeks 53.2% Stein EM, et al. Blood 2017; 130: Adverse effects Rate Hyperbilirubinemia 8% Differentiation 7% syndrome Anemia 7% Thrombocytopenia 5% Tumor lysis syndrome 3% Decreased appetite 2% Leukocytosis 1% Relatively few hematological toxicities Financial toxicity: $24,872 per month

48 Therapy Induction midostaurin CPX 351 Consolidation High dose cytarabine Allogeneic stem cell transplant High dose cytarabine + midostaurin Cure Diagnosis Reinduction CLAG±M FLAG IDA MEC High dose cytarabine CPX 351 consolidation Palliation Azacitidine Decitabine Low dose subcutaneous cytarabine Best supportive care Ivosidenib or enasidenib (relapsed/refractory)

49 A brief word about gemtuzumab ozogamicin An anti CD33 monoclonal antibody complexed to a cytotoxic molecule Dosing: Newly diagnosed AML, intensive therapy Induction: gemtuzumab on Days 1, 4, and 7 Consolidation: chemotherapy + gemtuzumab 3 mg/m2 IV on Day 1 Newly diagnosed AML, not fit for intensive therapy Loading: gemtuzumab on Days 1 and 3 Maintenance: gemtuzumab every 4 weeks Relapsed/refractory AML Gemtuzumab on Days 1, 4, 7 Adverse effects: thrombocytopenia, infection, hepatic toxicity after transplant

50 Diagnosis Therapy Induction midostaurin CPX gemtuzumab Consolidation High dose cytarabine Allogeneic stem cell transplant High dose cytarabine + midostaurin CPX 351 consolidation Chemotherapy + gemtuzumab Cure Reinduction CLAG±M FLAG IDA MEC High dose cytarabine Gemtuzumab Palliation Azacitidine Decitabine Low dose subcutaneous cytarabine Best supportive care Ivosidenib or enasidenib (relapsed/refractory) Gemtuzumab

51 Summary The therapeutic landscape for AML has changed little in the last two decades Since April 2017, several new drugs have entered clinical use that are specific to disease cytogenetics and molecular abnormalities Midostaurin (Apr 28, 2017) Enasidenib (Aug 1, 2017) Daunorubicin cytarabine liposome (Aug 3, 2017) Gemtuzumab ozogamicin (Sep 1, 2017) Ivosidenib (Jul 20, 2018) These drugs have unique indications and toxicities

52 Learning assessment question DD is a 65 year old female patient. Her PMH is notable for mantle cell lymphoma diagnosed in She has received a number of lines of chemotherapy, including bendamustine, rituximab, lenalidomide, lomustine, etoposide, cytarabine, melphalan, and ibrutinib. She has been in remission from her mantle cell lymphoma for about 2 years. Now she has been newly diagnosed with AML with myelodysplastic related changes. It has complex cytogenetics, including del(5q) and 7, with a loss offunction mutation in TP57. She is otherwise in good health, with a good performance status, and wants curative treatment. Among currently FDAapproved therapies, which option is most likely to achieve this goal: A. Gemtuzumab ozogamicin (Mylotarg) B. Daunorubicin cytarabine liposome (Vyxeos) C. Enasidenib (Idhifa) D. Induction chemotherapy with the 7+3 regimen, consolidation with CAR T cell therapy E. Induction chemotherapy with the 7+3 regimen, followed by midostaurin (Rydapt)

53 This is not the end This is only the beginning

54 New Drugs Update: Immunotherapy Katie A. Karkowski, PharmD, BCOP Clinical Pharmacist Lead Hematology/Oncology Dartmouth Hitchcock Medical Center November 2, 2018

55 Introduction Disclosures I have no conflicts of interest to disclose. Learning Objectives Summarize the safety and efficacy data for recently approved immunotherapy agents Presentation Outline Immune Checkpoint Inhibitor Updates Blinatumomab Updates Chimeric antigen receptor (CAR) T Cells

56 Learning Assessment Excluding clinical trials and considering only FDAapproved indications for tisagenlecleucel and axicabtagene ciloleucel Which of the following patients would be appropriate for referral for CAR T cell therapy? A. A 3 yr old male with newly diagnosed B cell ALL B. A 67 yr old female with PCNSL who has relapsed following two prior lines of therapy C. A 64 yr old male with DLBCL who has relapsed following two prior lines of therapy D. A 59 yr old female with MM who has relapsed following three prior lines of therapy

57 Immune Checkpoint Inhibitor Updates

58 Immune Checkpoint Inhibitors Pembrolizumab Nivolumab Atezolizumab Avelumab Durvalumab Cervical Colorectal Gastric Head and Neck Hodgkin Lymphoma Melanoma Non Hodgkin Lymphoma NSCLC Urothelial MSI high and MMR deficient Colorectal Head and Neck Hepatocellular Hodgkin Lymphoma Melanoma Renal Cell SCLC NSCLC Urothelial NSCLC Urothelial *Renal Cell *SCLC Merkel Cell Urothelial NSCLC *Merkel Cell *off label use *off label use Gold Standard, Inc. Clinical Pharmacology [database online]. Available at: Accessed: October 18, 2018.

59 Cemiplimab rwlc 1. Metastatic cutaneous squamous cell carcinoma (CSCC) 2. Locally advanced CSCC not eligible for curative surgery or curative radiation ORR = 47.2% (3.7% CR and 43.5% PR) DOR = months (61% had DOR > 6 months) Dose = 350 mg IV over 30 minutes every 3 weeks 1. Immune mediated adverse reactions 2. Infusion related reactions Libtayo (cemiplimab rwlc) [prescribing information]. Tarrytown, NY: Regeneron; September 2018.

60 Blinatumomab Updates

61 Blinatumomab 2014 Ph Relapsed or Refractory B Cell ALL 2017 Ph+ Relapsed or Refractory B Cell ALL 2018 B Cell ALL in CR with MRD 0.1% 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% The TOWER Study 52% 24% % of Patients in CR but MRD+ Blinatumomab SOC Chemo The BLAST Study Enrolled 86 MRD positive patients in first or second CR 70 patients (81.4%) achieved MRD negative status Median number of cycles = 2 Blincyto (blinatumomab) [prescribing information]. Thousand Oaks, CA: Amgen Inc; May 2018.

62 Blinatumomab REMS Cycle 1 Cycle 2 5 Cycle 6 9 Cycle 1 4 Fixed dosing for R/R patients weighing 45 kg Days 1 7 Days 8 28 Days mcg/day 28 mcg/day 14 days off Days 1 28 Days mcg/day 14 days off Days 1 28 Days mcg/day 56 days off Fixed dosing for MRD+ patients weighing 45 kg Days 1 28 Days mcg/day 14 days off Blincyto (blinatumomab) [prescribing information]. Thousand Oaks, CA: Amgen Inc; May 2018.

63 Blinatumomab REMS Cytokine Release Syndrome Median onset = 2 days Fever, headache, nausea, asthenia, hypotension, increased ALT/AST/bilirubin, and DIC Grade 3 Hold and Grade 4 Discontinue Neurotoxicity Median onset 2 weeks Headache, tremor, encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion, disorientation, and coordination and balance disorders Grade 3 Hold Grade 4 or > 1 Seizure Discontinue Blincyto (blinatumomab) [prescribing information]. Thousand Oaks, CA: Amgen Inc; May 2018.

64 CAR T Cell Therapy

65 CAR T Cell Therapy Leukapheresis Viral Vector Cells Gain CARs Proliferation Reinfusion Tisagenlecleucel Patients up to 25 years of age with B cell precursor ALL that is refractory or in second or later relapse. Adults with relapsed or refractory large B cell lymphoma after two or more lines of systemic therapy. Not for use for PCNSL. Axicabtagene Ciloleucel Adults with relapsed or refractory large B cell lymphoma after two or more lines of systemic therapy. Not for use for PCNSL. Kymriah (tisagenlecleucel) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; May Yescarta (axicabtagene ciloleucel) [prescribing information]. Santa Monica, CA: Kite Pharma; October 2017.

66 Ongoing Clinical Trials Hematologic Malignancies Adult Acute Lymphoblastic Leukemia Solid Tumors Tumor infiltrating lymphocytes Chronic Lymphocytic Leukemia Acute Myeloid Leukemia Multiple Myeloma

67 CAR T Cell Supportive Care Patient Identification Collection Manufacturing Chemotherapy, Reinfusion, Acute Monitoring Long Term Monitoring Acute Monitoring: The REMS require patients to remain within proximity of the certified healthcare facility for at least 4 weeks following reinfusion. Hypersensitivity reactions CRS median time to onset = 2 3 days Neurotoxicity median time to onset = 4 6 days Kymriah (tisagenlecleucel) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; May Yescarta (axicabtagene ciloleucel) [prescribing information]. Santa Monica, CA: Kite Pharma; October 2017.

68 CAR T Cell Supportive Care Prolonged Cytopenias Grade 3 cytopenias not resolved by day 28 are common Thrombocytopenia = 18 40% Neutropenia = 15 40% Hypogammaglobulinemia Monitor IgG levels and consider supplementation with IVIG if IgG < 400 mg/dl Serious Infections Infections occur in a high percentage of patients (38 55%) Provide patients with bacterial, viral, fungal, and pneumocystis prophylaxis Kymriah (tisagenlecleucel) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; May Yescarta (axicabtagene ciloleucel) [prescribing information]. Santa Monica, CA: Kite Pharma; October 2017.

69 CAR T Cell Supportive Care Medications Seizure prophylaxis until day +30 or +60 Levetiracetam 750 mg orally twice daily Fungal prophylaxis until ANC > 500 cells/mcl Fluconazole 400 mg orally once daily Bacterial prophylaxis until ANC > 500 cells/mcl Levofloxacin 750 mg orally once daily Viral prophylaxis until CD4 > 200 cells/mcl Acyclovir 800 mg orally twice daily Valacyclovir 500 mg orally twice daily Pneumocystis pneumonia prophylaxis from day +30 until CD4 > 200 cells/mcl Sulfamethoxazole/trimethoprim double strength once daily or three times weekly Mahmoudjafari Z, Hawks KG, Hsieh AA, et al. Biol Blood Marrow Transplant Sep 25. Prevention and Treatment of Cancer Related Infections v Accessed October 21, 2018.

70 Learning Assessment Excluding clinical trials and considering only FDAapproved indications for tisagenlecleucel and axicabtagene ciloleucel Which of the following patients would be appropriate for referral for CAR T cell therapy? A. A 3 yr old male with newly diagnosed B cell acute lymphoblastic leukemia B. A 67 yr old female with primary central nervous system lymphoma who has relapsed following two prior lines of therapy C. A 64 yr old male with diffuse large B cell lymphoma who has relapsed following two prior lines of therapy D. A 59 yr old female with multiple myeloma who has relapsed following three prior lines of therapy

71 Questions?