TREATMENT ADHERENCE ESSENTIALS

FOR NURSES

A comprehensive pocket guide created in partnership with nurses at AstraZeneca

PATIENTS MAY BE ABLE TO GET HELP PAYING FOR THEIR ASTRAZENECA TREATMENT THROUGH THE

ASTRAZENECA ACCESS 360TM PROGRAM

AstraZeneca Access 360 is a trademark of the AstraZeneca group of companies.©2020 AstraZeneca. All rights reserved. US-42287 7/20

References: 1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019. 2. IMBRUVICA [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2020. 3. BRUKINSA [package insert]. San Mateo, CA: BeiGene USA, Inc.; 2019. 4. Singh SP, Dammeijer F, Hendriks RW. Role of Bruton’s tyrosine kinase in B cells and malignancies. Molecular Cancer. 2018;17(1):57. 5. Low red blood cell counts (anemia). American Cancer Society. Accessed July 13, 2020. https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/low-blood-counts/anemia.html 6. Cancer fatigue: why it occurs and how to cope. Mayo Clinic. Accessed July 13, 2020. https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/cancer-fatigue/art-20047709 7. Common Terminology Criteria for Adverse Events (CTCAE). US Department of Health and Human Services. Accessed July 13, 2020. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf 8. Bleeding and bruising (thrombocytopenia) and cancer treatment. National Cancer Institute. Accessed July 13, 2020. https://www.cancer.gov/about-cancer/treatment/side-effects/bleeding-bruising 9. Diarrhea. Cancer.net. Accessed July 13, 2020. https://www.cancer.net/coping-with-cancer/physical-emotional-and-social-effects-cancer/managing-physical-side-effects/diarrhea 10. Headaches. Cancer.net. July 13, 2020. https://www.cancer.net/coping-with-cancer/physical-emotional-and-social-effects-cancer/managing-physical-side-effects/headaches 11. Castillo JJ, Treon SP. What is new in the treatment of Waldenstrom macroglobulinemia? Leukemia. 2019;33(11):2555-2562. 12. Lustberg MB. Management of neutropenia in cancer patients. Clin Adv Hematol Oncol. 2012;10(12):825–826. 13. Preventing infections in cancer patients. Centers for Disease Control and Prevention. Accessed July 13, 2020. https://www.cdc.gov/cancer/preventinfections/symptoms.htm 14. Gauer RL, Braun MM. Thrombocytopenia. Am Fam Physician. 2012;85(6):612-622. 15. Low blood cell count. Mayo Clinic. Accessed July 13, 2020. https://www.mayoclinic.org/symptoms/low-white-blood-cell-count/basics/definition/sym-20050615 16. Low white blood cell count. Breastcancer.org. Accessed July 13, 2020. https://www.breastcancer.org/treatment/side_effects/low_white_blood_cell 17. Musculoskeletal pain. Cleveland Clinic. Accessed July 13, 2020. https://my.clevelandclinic.org/health/diseases/14526-musculoskeletal-pain 18. Musculoskeletal pain: management and treatment. Cleveland Clinic. Accessed July 13, 2020. https://my.clevelandclinic.org/health/diseases/14526-musculoskeletal-pain/management-and-treatment 19. NCI dictionary of cancer terms – rash. National Cancer Institute. Accessed July 13, 2020. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/798604 20. Skin conditions. Cancer.net. Accessed July 13, 2020. https://www.cancer.net/coping-with-cancer/physical-emotional-and-social-effects-cancer/managing-physical-side-effects/skin-conditions 21. Balentine JR, Siamak NN, Shiel WC Jr. Upper respiratory tract infection (URTI). MedicineNet. Accessed July 13, 2020. https://www.medicinenet.com/upper_respiratory_infection/article.htm 22. Adherence to long-term therapies: evidence for action. World Health Organization. Published 2003. Accessed July 13, 2020. https://apps.who.int/iris/bitstream/handle/10665/42682/9241545992.pdf 23. Neuss MN, Gilmore TR, Belderson KM, et al. 2016 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards, including standards for pediatric oncology. J Oncol Pract. 2016;12(12):1262-1271.

Healthcare providers (HCPs) are encouraged to report AEs to the FDA. To report suspected adverse reactions, contact AstraZeneca at 1-800-236-9933 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

2 3

Introduction

TREATMENT ADHERENCE: HELPING PATIENTS STAY ON TRACK

BTKis FOR B-CELL MALIGNANCIES

Dear healthcare professional,

As you may know, adherence is a fundamental aspect of a patient’s treatment plan. Without it, treatment success may be put at serious risk.

We play a pivotal role in helping patients stay on track during treatment. The ability to bridge the gap between prescriber and patient, and educate patients during treatment, is crucial to improving and maintaining adherence.

Our oncology team is here to support your hard work and efforts to partner with patients. Use this guide to help you in your discussions about treatment adherence. You can also get in touch with your local AstraZeneca hematology Oncology Nurse Educator (ONE).

—The AstraZeneca Hematology ONE Team

If patients have either chronic lymphocytic leukemia (CLL) or relapsed/refractory mantle cell lymphoma (MCL), Bruton tyrosine kinase inhibitors (BTKis) are one of the treatments that oncologists can prescribe.1-3

CLL and MCL are cancers that start in B cells, and an enzyme (or kinase) called Bruton tyrosine kinase (BTK) contributes to the growth and survival of these cells. BTKis help stop growth and survival signals to B cells by inhibiting BTK, causing malignant B cells to die.4

BTKis for CLL or relapsed/refractory MCL are taken orally. Following the recommended dosing regimen enables sustained inhibition of BTK, which is why it’s important for patients to take BTKis as prescribed.1-3

BTKi adverse events (AEs)

AEs can happen with any oncology medication. The AEs shown here are representative of the most common (≥30%) AEs in patients with B-cell malignancies treated with FDA-approved BTKis. Knowing which AEs could occur and how to address them can help patients make the most of their treatment. Note: only the AEs in bold below are common to all 3 FDA-approved BTKis.1-3

MOST COMMON (≥30%) AEs AMONG FDA-APPROVED BTKis1-3

Anemia

Bruising

Leukopenia

Diarrhea

Fatigue

Headache

Neutropenia

Rash

Thrombocytopenia

Upper respiratory tract infection

Musculoskeletal pain

Other potential AEs of clinical interest with certain but not all BTKis include lymphocytosis, myalgia, arthralgia, hypertension, and atrial fibrillation. Please consult the Prescribing Information for individual BTKis for more information about AEs, as well as the effect of food, drug interactions (including strong and moderate CYP3A inhibitors and inducers), and pathway interactions.1

In addition, serious and potentially fatal AEs have been reported. Consult the Warnings and Precautions sections of Prescribing Information for individual BTKis for more information.1-3

FOR TIPS ON HOW TO MANAGE THESE AEs, PLEASE SEE THE NEXT PAGE.

Most common AEs are based on each product’s specific pooled safety population for B-cell malignancies as reported in each product's respective Prescribing Information.

4 5

AE management

Leukopenia

A low white blood cell count, generally defined as less than 4000/μL. Signs and symptoms include those of infection, such as a fever or chills15,16

✦ If a patient presents with any signs or symptoms of leukopenia, please contact the relevant healthcare provider for management

Low blood cell count. Signs and symptoms include but are not limited to increased heartbeat, extreme tiredness, and shortness of breath5

✦ If a patient presents with any signs or symptoms of anemia, please contact the relevant healthcare provider for management5

Anemia Diarrhea

Typified by frequent and loose or watery bowel movements9

✦ Counsel patients on diarrhea with possible tips such as drinking clear liquids, avoiding fatty foods and alcohol, and eating small meals9

Fatigue

Often characterized by feeling tired, weak, or exhausted6

✦ Suggestions to alleviate fatigue may include conserving energy by drinking fluids and eating well, as well as light exercise6

Any exercise should be approved by the patient's primary care physician.

Headache

Characterized by a painful sensation in any part of the head10

✦ Taking over-the-counter acetaminophen and drinking caffeinated drinks may be helpful10,11

Bruising

Occurs when an injury causes blood to leak into surrounding tissues in the body7

✦ Ice may be applied to the bruise. Advise patients to consult with the relevant healthcare provider if bruising and bleeding is occurring easily8

Neutropenia

Generally defined as an absolute neutrophil count of less than 1500 cells/mm³. Signs and symptoms include but are not limited to signs of infection, such as a fever or chills12,13

✦ If a patient presents with any signs or symptoms of neutropenia, please contact the relevant healthcare provider for management13

Rash

Inflammation that leads to red, dry, and/or itchy skin19

✦ Advise patients to use mild soaps or skin products. Corticosteroids may be prescribed if needed20

Upper respiratory tract infection (URTI)

Musculoskeletal pain

Signs and symptoms of URTI include cough, runny nose, sore throat, and nasal congestion21

✦ If a patient presents with any of these signs or symptoms, please contact the relevant healthcare provider for management21

Muscle and bone pain that feels like aches or stiffness occurring in an isolated area or across the entire body17

✦ Have patients apply heat or cold to affected areas, and educate patients about stretching or strengthening and conditioning exercises18

Thrombocytopenia

Defined by a platelet count of less than 150 × 109/L. Signs and symptoms include but are not limited to unexpected bruising, small purple or red spots under the skin (petechiae), or bleeding14

✦ If a patient presents with any signs or symptoms of thrombocytopenia, please contact the relevant healthcare provider for management14

Please note that these management considerations are not BTKi product label recommendations.Each patient’s clinical history may affect AE management. Patients should be treated based on their individual needs.

Consult with appropriate healthcare providers for management of these AEs.

BTKi AE MANAGEMENT CONSIDERATIONS

6 7

Barriers

BARRIERS TO TREATMENT ADHERENCE

If patients aren’t taking their treatment as prescribed, you may need to understand the underlying causes. Below are some potential reasons why patients may be non-adherent with their medications.

Treatment

Patient history

Healthcare system

Socioeconomic

Do patients understand why they are on a treatment?22

How are patients feeling physically, and what past behavioral traits may

lead to non-adherence?22

Are patients comfortable talking about potential concerns with

their healthcare team?22

Do patients have any financial concerns?22

By uncovering the reasons why patients may not be taking their therapy, you can help educate them and ensure they feel empowered throughout their treatment journey.

The latter sections of this guide will examine potential barriers to treatment adherence and provide checklists to help you talk to your patients.

Initial visit assessment23

Effective patient counseling

Asking questionsConsider asking patients questions to understand any potential barriers to long-term treatment adherence. Asking patients about specific points from your conversation may help you uncover what the patient has understood from the conversation and what they are still confused about.

“What have you learned from our conversation today?” is a good example of an open-ended question that allows you to learn what key takeaways the patient remembers.

During the initial visit with patients taking an oral treatment, ask about the following to ensure they understand their treatment plan and uncover any questions they may have:

✦ The name of the disease they have and treatment they are taking✦ How they should take their treatment (including any other treatments or foods

to avoid)✦ This may include confirming if patients are taking any antacids, H2-receptor

antagonists, CYP3A inhibitors or inducers, or proton pump inhibitors1-3

✦ What they should do if a dose is missed✦ How long they should take their treatment for✦ Where they plan to store their medication✦ How often they should be refilling their prescription✦ What potential AEs they should expect and when, and who to contact when

they experience an AE✦ Assess the risk of AEs of special interest, such as atrial fibrillation

✦ Whether they have questions about paying for their medications✦ If they know when to return for a follow-up visit

8 9

Treatment factors

TREATMENT FACTOR ADHERENCE CHECKLIST

What do you expect from this treatment?

What is your plan for taking your treatment on a regular basis?

What do you plan to do if you miss a dose?

What is your plan for tracking potential side effects?

What medications are you currently taking (including any vitamins, herbs, or other supplements)?

✦ Encourage patients to keep a record of any AE they experience ✦ Tell patients who they should contact if they do experience an AE

✦ Ensure you know how many other treatments the patient may be taking, what conditions they are for, and how often the patient is taking them per day

✦ Make sure patients know when and how to manage taking multiple medications, particularly if there is a potential interaction

✦ Ask whether patients are having any difficulty taking other treatments (eg, trouble swallowing)

Healthcare providers (HCPs) are encouraged to report AEs to the FDA. To report suspected adverse reactions, contact AstraZeneca at 1-800-236-9933 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

✦ Make sure patients know what AEs to expect, as well as what to do if they experience AEs (for example, who they should call)

✦ Confirm that patients know the dosing schedule✦ Share tips with patients to help them remember to take their medications, such as

using one or more of the following:✦ Treatment calendar✦ Daily medication checklist✦ Treatment journal✦ Electronic reminders, such as calendar reminders and alarms✦ Pillboxes

✦ Encourage patients to have their caregivers or friends help them stay on track through actions like the following:✦ Reminding patients about when to take their medications✦ Reminding patients to pack enough medication when traveling or when they are

otherwise away from home✦ Ensure patients are closely tracking the doses they’re taking

✦ Patients should keep the tracker in an obvious place so they see it every day

✦ Remind patients not to get discouraged if they miss a dose. Counsel them to be patient with themselves

✦ Advise patients on what they should do if they miss a dose

10 11

Additional factors

HEALTHCARE SYSTEM FACTOR ADHERENCE CHECKLIST

✦ Give patients useful resources and help them access the type of information that can empower them to comply with their treatment

✦ Contact your AstraZeneca Hematology ONE Team to request any supplementary patient resources, including tools that can assist patients on BTKi treatments

✦ Establish what the best lines of communication are for the patient (eg, texting vs calling), as well as the frequency of contact, to ensure patients feel connected with the broader healthcare team

What additional information about your treatment can I offer that would be helpful to you right now?

✦ Make sure the patient has a reliable way to get to the doctor’s office✦ If in doubt, ask if anyone in the patient's family or social circle can provide transportation

✦ Ensure you understand the insurance vetting process: who will call the patient with co-pay information, and who will obtain foundation funding or a co-pay card, if needed

✦ Always remember to provide any co-pay/financial support information about the treatment when it’s first prescribed

✦ Remind patients that many manufacturers have specific programs to help patients pay for their treatments

✦ Remind patients they can consult a number of foundations that can provide financial assistance, including:

Information about independent third-party foundation financial assistance can be found by visiting https://www.myaccess360.com/calquence-acalabrutinib/patient-affordability.html, and clicking on “Learn More” in the Foundations bucket on the right side of the page. These foundations are not associated with AstraZeneca.

SOCIOECONOMIC FACTOR ADHERENCE CHECKLIST

How will you fill your prescription? Does your insurance cover your treatment?

What is the best way for me to follow up with you?

What kind of support do you have for treatment?

What help do you need with submitting insurance claims or working with your insurance company?

American Cancer Societyhttps://www.cancer.org/treatment/finding-and-paying-for-treatment

CancerCare® Co-Payment Assistance Foundation http://cancercarecopay.org

HealthWell Foundation www.healthwellfoundation.org

The Leukemia & Lymphoma Society® Co-Pay Assistance Program www.lls.org/copay

PAN Foundation www.panfoundation.org

Independent Third-party Foundation Financial Assistance

TREATMENT ADHERENCE ESSENTIALS

FOR NURSES

A comprehensive pocket guide created in partnership with nurses at AstraZeneca

PATIENTS MAY BE ABLE TO GET HELP PAYING FOR THEIR ASTRAZENECA TREATMENT THROUGH THE

ASTRAZENECA ACCESS 360TM PROGRAM

AstraZeneca Access 360 is a trademark of the AstraZeneca group of companies.©2020 AstraZeneca. All rights reserved. US-42287 7/20

References: 1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019. 2. IMBRUVICA [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2020. 3. BRUKINSA [package insert]. San Mateo, CA: BeiGene USA, Inc.; 2019. 4. Singh SP, Dammeijer F, Hendriks RW. Role of Bruton’s tyrosine kinase in B cells and malignancies. Molecular Cancer. 2018;17(1):57. 5. Low red blood cell counts (anemia). American Cancer Society. Accessed July 13, 2020. https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/low-blood-counts/anemia.html 6. Cancer fatigue: why it occurs and how to cope. Mayo Clinic. Accessed July 13, 2020. https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/cancer-fatigue/art-20047709 7. Common Terminology Criteria for Adverse Events (CTCAE). US Department of Health and Human Services. Accessed July 13, 2020. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf 8. Bleeding and bruising (thrombocytopenia) and cancer treatment. National Cancer Institute. Accessed July 13, 2020. https://www.cancer.gov/about-cancer/treatment/side-effects/bleeding-bruising 9. Diarrhea. Cancer.net. Accessed July 13, 2020. https://www.cancer.net/coping-with-cancer/physical-emotional-and-social-effects-cancer/managing-physical-side-effects/diarrhea 10. Headaches. Cancer.net. July 13, 2020. https://www.cancer.net/coping-with-cancer/physical-emotional-and-social-effects-cancer/managing-physical-side-effects/headaches 11. Castillo JJ, Treon SP. What is new in the treatment of Waldenstrom macroglobulinemia? Leukemia. 2019;33(11):2555-2562. 12. Lustberg MB. Management of neutropenia in cancer patients. Clin Adv Hematol Oncol. 2012;10(12):825–826. 13. Preventing infections in cancer patients. Centers for Disease Control and Prevention. Accessed July 13, 2020. https://www.cdc.gov/cancer/preventinfections/symptoms.htm 14. Gauer RL, Braun MM. Thrombocytopenia. Am Fam Physician. 2012;85(6):612-622. 15. Low blood cell count. Mayo Clinic. Accessed July 13, 2020. https://www.mayoclinic.org/symptoms/low-white-blood-cell-count/basics/definition/sym-20050615 16. Low white blood cell count. Breastcancer.org. Accessed July 13, 2020. https://www.breastcancer.org/treatment/side_effects/low_white_blood_cell 17. Musculoskeletal pain. Cleveland Clinic. Accessed July 13, 2020. https://my.clevelandclinic.org/health/diseases/14526-musculoskeletal-pain 18. Musculoskeletal pain: management and treatment. Cleveland Clinic. Accessed July 13, 2020. https://my.clevelandclinic.org/health/diseases/14526-musculoskeletal-pain/management-and-treatment 19. NCI dictionary of cancer terms – rash. National Cancer Institute. Accessed July 13, 2020. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/798604 20. Skin conditions. Cancer.net. Accessed July 13, 2020. https://www.cancer.net/coping-with-cancer/physical-emotional-and-social-effects-cancer/managing-physical-side-effects/skin-conditions 21. Balentine JR, Siamak NN, Shiel WC Jr. Upper respiratory tract infection (URTI). MedicineNet. Accessed July 13, 2020. https://www.medicinenet.com/upper_respiratory_infection/article.htm 22. Adherence to long-term therapies: evidence for action. World Health Organization. Published 2003. Accessed July 13, 2020. https://apps.who.int/iris/bitstream/handle/10665/42682/9241545992.pdf 23. Neuss MN, Gilmore TR, Belderson KM, et al. 2016 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards, including standards for pediatric oncology. J Oncol Pract. 2016;12(12):1262-1271.

Healthcare providers (HCPs) are encouraged to report AEs to the FDA. To report suspected adverse reactions, contact AstraZeneca at 1-800-236-9933 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.