What is Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma?¹

Lymphoma is the most common blood cancer. The main forms of lymphoma are classified as Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL), which includes several B-cell lymphomas and T-cell lymphomas
Lymphoma occurs when cells of the immune system called lymphocytes, a type of white blood cell, uncontrollably grow and multiply
The body has two main types of lymphocytes that can develop into lymphomas: B lymphocytes (B cells) and T lymphocytes (T cells)
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are forms of non-Hodgkin lymphoma that arise from B lymphocytes
When most of the cancer cells are located in the bloodstream and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved
When the cancer cells are located mostly in the lymph nodes and are rare in the blood, the disease is called SLL

What is relapsed or refractory CLL/SLL?²

When CLL/SLL returns after medical care and treatment, this is called a relapse.
When cancerous cells are resistant, do not respond to a treatment, or return within six months of treatment, they are called refractory.

https://www.lls.org/leukemia/chronic-lymphocytic-leukemia/treatment/relapsed-and-refractory

Helpful Tips for People with CLL/SLL

What you can do for your health.

Living with CLL or SLL can be unpredictable. How you feel may change from day to day. You’re also an individual, so your body will react differently—both to the disease and the treatments your doctor prescribes. However, there are some steps you can take to try to stay healthy. Use these tips as a starting point for discussion with your healthcare team.

Follow Healthy Nutritional Guidelines

Eating healthy is important. To ensure the food you’re eating is helpful to your body:

Talk to your doctor about foods to eat, foods to avoid, portions, and frequency of meals
Be cautious with raw or uncooked foods
Stay hydrated
Avoid strong or overpowering smells that may trigger nausea
Talk to your doctor if you experience nausea

Try to Avoid Infections and Fever

Low white blood cell counts can increase your risk of infection and fever. To reduce your risk:

Remind people around you to wash their hands frequently
Take precautions to minimize your exposure to bacteria and viruses

Rest When Needed

Getting rest is very important to your overall health. To make sure you’re getting enough rest:

Talk with your doctor if you are experiencing tiredness or fatigue and ask how to improve your sleep quality, if needed
Avoid drinking caffeine or alcohol right before you go to sleep; do something that will relax you instead
Try to have a consistent bedtime and avoid long naps during the day
Talk to your doctor about how to add appropriate exercise into your routine. Physical activity may decrease feelings of fatigue and encourage healthy sleep patterns

Always remember to talk with your doctor about how you are feeling during treatment. It is important that they know how your treatment is affecting you so that adjustments can be made if needed.

IMPORTANT SAFETY INFORMATION

Treatment-related mortality occurred in 15% of COPIKTRA treated patients.
Fatal and/or serious infections occurred in 31% (4% fatal) of COPIKTRA-treated patients. Monitor for signs and symptoms of infection. Withhold COPIKTRA if infection is suspected.
Fatal and/or serious diarrhea or colitis occurred in 18% (<1% fatal) of COPIKTRA-treated patients. Monitor for the development of severe diarrhea or colitis. Withhold COPIKTRA.
Fatal and/or serious cutaneous reactions occurred in 5% (<1% fatal) of COPIKTRA-treated patients. Withhold COPIKTRA.
Fatal and/or serious pneumonitis occurred in 5% (<1% fatal) of COPIKTRA-treated patients. Monitor for pulmonary symptoms and interstitial infiltrates. Withhold COPIKTRA.

WARNINGS AND PRECAUTIONS

Treatment-related Mortality: In a randomized controlled study in patients with relapsed or refractory CLL or SLL, treatment with COPIKTRA caused increased treatment-related mortality. With extended follow-up with a median of 63 months, treatment-related deaths occurred in 15% (23/158) of those patients in the overall population. In the indicated patient population, patients with relapsed or refractory CLL or SLL after at least two prior lines of systemic therapy, treatment related deaths following treatment with COPIKTRA occurred in 14% (13/93) of patients. The most common cause of the treatment-related deaths were infections, which occurred in 9% and 11% of patients with relapsed or refractory CLL following at least one or two prior systemic therapies, respectively. COPIKTRA is not indicated and is not recommended for any patients in the initial or second-line treatment setting.

Infections: Serious, including fatal (18/442, 4%), infections occurred in 31% of patients receiving COPIKTRA. The most common serious infections were pneumonia, sepsis, and lower respiratory infections. Median time to onset of any grade infection was 3 months, with 75% of cases occurring within 6 months. Treat infections prior to initiation of COPIKTRA. Advise patients to report new or worsening signs and symptoms of infection. Cases of Pneumocystis jirovecii pneumonia (PJP) (1%) and cytomegalovirus (CMV) reactivation/infection (1%) occurred in patients taking COPIKTRA. Provide prophylaxis for PJP during treatment and following completion of treatment until the absolute CD4+ T cell count is greater than 200 cells/μL. Consider prophylactic antivirals during COPIKTRA treatment to prevent CMV infection including CMV reactivation.

Diarrhea or Colitis: Serious, including fatal (1/442; 0.2%), diarrhea or colitis occurred in 18% of patients receiving COPIKTRA. Median time to onset of any grade diarrhea or colitis was 4 months, with 75% of cases occurring by 8 months. The median event duration was 0.5 months. Advise patients to report any new or worsening diarrhea.

Cutaneous Reactions: Serious, including fatal (2/442; 0.5%), cutaneous reactions occurred in 5% of patients receiving COPIKTRA. Fatal cases included drug reaction with eosinophilia and systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN). Median time to onset of any grade cutaneous reaction was 3 months with a median event duration of 1 month. Presenting features for the serious events were primarily described as pruritic, erythematous, or maculo-papular. Less common presenting features include exanthem, desquamation, erythroderma, skin exfoliation, keratinocyte necrosis, and papular rash. Advise patients to report new or worsening cutaneous reactions.

Pneumonitis: Serious, including fatal (1/442; 0.2%), pneumonitis without an apparent infectious cause occurred in 5% of patients receiving COPIKTRA. Median time to onset of any grade pneumonitis was 4 months with 75% of cases occurring within 9 months. The median event duration was 1 month with 75% of cases resolving by 2 months.

Hepatotoxicity: Grade 3 and 4 ALT and/or AST elevation developed in 8% and 2%, respectively, of patients receiving COPIKTRA (N=442). Two percent of patients had both an ALT or AST > 3 X ULN and total bilirubin > 2 X ULN. Median time to onset of any grade transaminase elevation was 2 months with a median event duration of 1 month. Monitor hepatic function during treatment with COPIKTRA.

Neutropenia: Grade 3 or 4 neutropenia occurred in 42% of patients receiving COPIKTRA (N=442), with Grade 4 neutropenia occurring in 24% of all patients. Median time to onset of grade ≥3 neutropenia was 2 months. Monitor neutrophil counts at least every 2 weeks for the first 2 months of COPIKTRA therapy, and at least weekly in patients with neutrophil counts < 1.0 Gi/L (Grade 3-4).

Embryo-Fetal Toxicity: COPIKTRA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus and conduct pregnancy testing before initiating COPIKTRA treatment. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for 1 month after the last dose.

ADVERSE REACTIONS

B-cell Malignancies Summary

Fatal adverse reactions within 30 days of the last dose occurred in 8% (36/442) of patients treated with COPIKTRA 25 mg BID. Serious adverse reactions were reported in 289 patients (65%). The most frequent serious adverse reactions that occurred were infection (31%), diarrhea or colitis (18%), pneumonia (17%), rash (5%), and pneumonitis (5%). The most common adverse reactions (reported in ≥20% of patients) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain and anemia.

CLL/SLL

Fatal adverse reactions within 30 days of the last dose occurred in 12% (19/158) of patients treated with COPIKTRA and in 4% (7/155) of patients treated with ofatumumab. Serious adverse reactions were reported in 73% (115/158) of patients treated with COPIKTRA and most often involved infection (38%; 60/158) and diarrhea or colitis (23%; 36/158). The most common adverse reactions with COPIKTRA (reported in ≥20% of patients) were diarrhea or colitis, neutropenia, pyrexia, upper respiratory tract infection, pneumonia, rash, fatigue, nausea, anemia and cough.

For specific information on the management of the adverse reactions above, please review Dose Modifications for Adverse Reactions within the full Prescribing Information.

DRUG INTERACTIONS

CYP3A4 Inducers: Coadministration with a strong or moderate CYP3A inducer may reduce COPIKTRA efficacy. Avoid coadministration with strong or moderate CYP3A4 inducers.

CYP3A4 Inhibitors: Coadministration with a strong CYP3A4 inhibitor may increase the risk of COPIKTRA toxicities. Reduce COPIKTRA dose when coadministered with a strong CYP3A4 inhibitor.

CYP3A4 Substrates: Coadministration of COPIKTRA with sensitive CYP3A4 substrates may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A4 substrate.

Please see accompanying full Prescribing Information, including Boxed Warning.

To report Adverse Reactions during use of COPIKTRA, contact Secura Bio, call 1-844-9Secura or 1-844-973-2872 and/or to FDA at www.fda.gov/medwatch or call 1-800-FDA-1088.

USCPR2419101