A POwerful New Treatment for

Lymphoma

Pharmacy Hangman!

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http://www.rxlist.com/imbruvica-drug.htm

Imbruvica (ibrutinib)

PHARMACYCLICS, Inc

FDA Approval on November 13, 2013

Antineoplastic Tyrosine Kinase Inhibitor

Oral Capsule (140 mg)

Bottle (#90) = $9840 MCL ~8 mo = $80k CLL ~16 mo = $160k

http://images.ddccdn.com/images/pills/fio/PHC01400.JPG

Source: UpToDate

Mechanism of ActionBCR

BTK

PLC-gamma

MAPKActivation

PI3K/AKTActivation

Nuclear FactorActivation

Lyn

Syc

ibrutinib•Covalently binds to Cys(481) on BTK Active Site• Inhibits B-cell proliferation and survival

Source: Journal of Clinical Oncology

Alternate Treatment Plans

Early Case No Treatment Monitor Progression

Intermediate/Advanced Chemotherapy Rituximab Stem Cell Transplant

http://itpandme.com/wp-content/uploads/2013/08/mum-300x300.jpg

http://www.rescuepost.com/.a/6a00d8357f3f2969e2015392a0e1bb970b-pi

Source: Journal of Clinical Oncology

Clinical Trial Overview

Mantle Cell Lymphoma 111 patients 68 yo,

77% male, 92% caucasian

Overall Response = 65.8% (56-75) Complete = 17.1% Partial = 48.6%

Duration = 17.5 months

FDA

Approval

Source: New England Journal of Medicine

Clinical Trial Overview

Source: New England Journal of Medicine

Contraindications/Precautions

Contraindications NONE Listed

Precautions Bleeding Events Infections Hematological Effects Renal Toxicity Secondary Primary

Malignancies Hyperuricemia Renal Function Hepatic Function Elderly

Source: Package Insert

Interactions

Anticoagulant/Anti-Platelets NSAIDs, SSRIs

CYP3A4 Inducers Rifampin, Phenobarbital,

Tocilizumab, etc St John’s Wort

CYP3A4 Inhibitors Ketoconazole, Ritonavir,

Clarithromycin, Diltazem Grapefruit/Seville

Oranges

Source: Package Insert

https://encrypted-tbn2.gstatic.com/images?q=tbn:ANd9GcShSIWaXmbNFTSpEMZ5p_o1PMlMxoR5_L836nFQy8yle1Ldh58p

http://contraceptivesvsantibiotics.files.wordpress.com/2012/04/rifampin.jpg?w=490

http://pics2.ds-static.com/prodimg/40491/300.jpg

http://www.aicr.org/assets/images/foods-that-fight-cancer/grapefruit-and-half.jpg

Pregnancy/Lactation

Pregnancy Category D Adverse events

observed in animal studies

Lactation Unknown Not Recommended

http://americanpregnancy.org/content/uploads/2013/06/shutterstock_18257989.jpg

Source: Package Insert

What to Watch For

Common SE (%) Headache (19%) Dizziness (21%) Back Pain (37%) Diarrhea (63%) Lack of Appetite (21%) Constipation (25%)

Serious ADR (%) Peripheral Edema (35%) Rash (27%) Hemorrhage (63%) Neutropenia (54%) Infection (35%) Hyperuricemia (40%)

Source: Package Insert

Dosing

CLL = 420 mg qDAY

MCL = 560 mg qDAY Administer Orally

w/Water at Same Time Everyday

Reduce dose by 140 mg for Toxic Events

Interrupt treatment for Surgery

http://www.yaopha.com/wp-content/uploads/2013/11/Imbruvica_Ibrutinib-Capsule_Mantle-Cell-Lymphoma_Covalent-BTK-inhibitor_Pharmacyclics_Janssen.jpg

Source: Package Insert

Lecture Limerick™

I have a patient on Imbruvica

To treat his Mantle Lymphoma

He comes once a month

For blood tests and stuff

Cause the pill he takes at homa!

Recommendations

Second Line Treatment for: MCL – 540 mg PO qDay CLL – 480 mg PO qDay

Irreversible Inhibitor of BTK (primarily on B-cells)

Avoid use with CYP3A4 Inducers/Inhibitors

Carefully Monitor: Blood Counts, Renal/Hepatic Function, Bleeding, Infections, Second Primary Malignancy

http://www.rxlist.com/imbruvica-drug.htm

References

1. Ibrutinib: Drug information. In: Rose B, ed. Uptodate. Waltham, MA: UpToDate; 2014.

2. Imbruvica [Package Insert]. Sunnyvale, CA: Pharmacyclics, Inc; 2014.

3. Herman S, Gordon A, Hertlein E, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011;117(23):6287-6296.

4. Ponader S, Burger J. Bruton's tyrosine kinase: From X-linked agammaglobulinemia toward targeted therapy for B-cell malignancies. J Clin Oncol. 2014;32:1-10.

5. Rossi D, Gaidano G. Lymphocytosis and ibrutinib treatment of CLL. Blood. 2014;123:1772-1774.

6. Wang M, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. New Engl J Med. 2013;369(6):507-516.