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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 Action
BCR
BTK
PLC-gamma
MAPK
Activation
PI3K/AKT
Activation
Nuclear Factor
Activation
Ly
n
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
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 Johns Wort
CYP3A4 Inhibitors
Ketoconazole, Ritonavir,
Clarithromycin, Diltazem
Grapefruit/Seville Oranges
Source: Package Insert
https://encrypted-
tbn2.gstatic.com/images?q=tbn:ANd9GcShSIWaXmbNFTSpEMZ5p_o1PMlMxoR5_L83
6nFQy8yle1Ldh58p
http://contraceptivesvsantibiotics.files.wordpress.com/201
2/04/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.