Rituxan® (Rituximab) in Non-Hodgkin's Lymphoma

Full Prescribing Information, including Boxed WARNINGS
Medication Guide (79K/PDF)

Rituxan is the first targeted cancer medicine approved by the U.S. Food and Drug Administration (FDA). Rituxan is approved for people with certain types of non-Hodgkin's lymphoma. Over the past 10 years, the safety and efficacy of Rituxan has been documented in more than 300 Phase II/III clinical studies.

Non-Hodgkin's lymphoma is the sixth most frequently diagnosed cancer in the United States. Nearly 85 percent of cases are caused by cancerous B-cells, a type of white blood cell that is part of the body's immune system. When B-cells become cancerous they may lead to blood cancers including non-Hodgkin's lymphoma.

How Rituxan Works

• Rituxan targets a specific protein called CD20 located on the surface of B-cells. Rituxan is believed to work with the body's immune system to eliminate the CD20-positive, cancerous B-cells
• Rituxan does not target cells that develop into B-cells (B-cell progenitors) or those that produce antibodies (plasma cells)

Rituxan "Firsts" in Non-Hodgkin's Lymphoma

• Follicular, CD20-positive, B-cell non-Hodgkin's lymphoma: Rituxan is the first FDA-approved biologic medicine that when combined with a type of chemotherapy called CVP helps individuals with follicular, CD20-positive, B-cell non-Hodgkin's lymphoma (a slow-growing form of the disease) who have not received a prior medicine, live longer without their disease worsening (progression-free survival)
• Diffuse large B-cell lymphoma: Rituxan was the first FDA-approved medicine in 25 years to help individuals who had not received a prior treatment for their diffuse large B-cell lymphoma (an aggressive form of non-Hodgkin's lymphoma) live longer (overall survival)

Rituxan Indications Rituxan is indicated for the treatment of patients with:

• Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
• Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy
• Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy
• Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens

Rituxan's Clinical Studies in Non-Hodgkin's Lymphoma

RITUXAN INDICATION	CLINICAL TRIAL DATA
First-Line Non-Hodgkin's Lymphoma with Chemotherapy
Rituxan plus CVP chemotherapy increases the length of time individuals with untreated follicular non-Hodgkin's lymphoma lived without their disease worsening (progression-free survival)	In a Phase III study, patients who received Rituxan plus CVP chemotherapy improved the length of time they lived without their disease worsening by 127 percent over chemotherapy alone. Individuals who received Rituxan plus CVP lived for nearly three years (2.83 years) compared to the 15 months for those who received chemotherapy alone Data also show Rituxan plus CVP chemotherapy reduced the likelihood of follicular non-Hodgkin's lymphoma getting worse, returning or causing death Rituxan can cause serious side effects, including: Progressive Multifocal Leukoencephalopathy (PML), which is a rare brain infection. PML usually causes death or severe disability. PML usually happens in patients with weakened immune systems. PML can occur during treatment with Rituxan or after treatment has finished. There is no known treatment, prevention, or cure for PML. Infusion reactions: Patients may get hives, swelling, dizziness, blurred vision, drowsiness, headache, cough, wheezing, or have trouble breathing while receiving or after receiving Rituxan. Tumor Lysis Syndrome (TLS): TLS is caused by the fast breakdown of certain types of cancer cells. TLS can cause kidney failure and the need for dialysis treatment. Severe skin reactions: Patients may get painful sores on the skin or in the mouth, ulcers, blisters, or peeling skin while receiving or after receiving Rituxan.
Ongoing Treatment Following First-Line Chemotherapy
When used by itself following CVP chemotherapy, Rituxan reduces the likelihood of low-grade non-Hodgkin's lymphoma either getting worse, returning or causing death	A Phase III study showed Rituxan, when used after CVP chemotherapy, lowered the chance that the disease either got worse, returned or resulted in death by 51 percent when compared to observation alone
Relapsed or Refractory Non-Hodgkin's Lymphoma
Early and repeated use of Rituxan may extend the time people with low-grade or follicular non-Hodgkin's lymphoma live after the disease returned (relapsed) or didn't respond to treatment (refractory)	Study results showed that retreatment with Rituxan in patients who previously received the medicine resulted in a sustained decrease in the amount of cancer cells (durable response) in their blood. The response in retreatment was on average 50 percent longer than their initial treatment In another Phase III study, patients who received previous treatment for low-grade or follicular lymphoma either experienced a decrease in the number of cancer cells in their blood (48 percent overall response rate and 42 percent partial response rate) or had no traces of cancer cells in their blood (6 percent complete response) Other Phase III study results showed patients who received Rituxan for low-grade or follicular lymphoma experienced a decrease in the cancer cells in their blood (57 percent overall response rate and 43 percent partial response rate) or had no traces of cancer cells blood (14 percent complete response rate) Other serious and life-threatening side effects with Rituxan include: hepatitis B virus reactivation, heart problems, infections, and stomach and bowel problems. Common side effects during Rituxan infusions include: fever, headache, chills and shakes, nausea, itching, hives, cough, sneezing, and throat irritation or tightness.
First-Line Diffuse Large B-Cell Lymphoma
Rituxan plus CHOP chemotherapy has been shown to improve survival in individuals with diffuse large B-cell CD20-positive lymphoma in three separate Phase III studies	In one, Rituxan plus CHOP chemotherapy increased the time patients with previously untreated diffuse large CD20-positive B-cell lymphoma lived (overall survival) from 36 percent to 53 percent, compared to those who received chemotherapy alone, after seven years In another, Rituxan plus CHOP chemotherapy increased the time patients with untreated diffuse large CD20-positive B-cell lymphoma lived (overall survival) from 46 percent to 58 percent compared with chemotherapy alone, after five years An additional study showed Rituxan plus CHOP chemotherapy increased the likelihood of individuals with previously untreated diffuse large CD20-positive B-cell lymphoma living for two years from 63 percent to 74 percent and 86 percent to 95 percent respectively, compared to chemotherapy alone

Rituxan Development Program

• Rituxan is being studied in other types of CD20-positive blood cancers and disease areas

Important Safety Information, including Boxed WARNINGS Rituxan can cause serious side effects, some of which could be life-threatening:

• Progressive Multifocal Leukoencephalopathy (PML)
  PML is a rare brain infection that usually causes death or severe disability. Patients should call their doctor right away if they notice any new or worsening medical problems, such as a new or sudden change in thinking, walking, strength, vision, or other problems that have lasted over several days. PML can occur during treatment with Rituxan or after treatment has finished. There is no known treatment, prevention, or cure for PML.
• Infusion reactions. Patients should tell their doctor or get medical treatment right away if they get hives, swelling, dizziness, blurred vision, drowsiness, headache, cough, wheezing, or have trouble breathing while receiving or after receiving Rituxan.
• Tumor Lysis Syndrome (TLS). TLS is caused by the fast breakdown of certain types of cancer cells. TLS can cause kidney failure and the need for dialysis treatment. Patients receiving Rituxan for Non-Hodgkin's Lymphoma (NHL) may get TLS.
• Severe skin reactions. Patients should tell their doctor or get medical treatment right away if they get any of these symptoms: painful sores on their skin or in their mouth, ulcers, blisters, or peeling skin while receiving or after receiving Rituxan.

Rituxan can cause other serious and life-threatening side effects, including:

• Hepatitis B virus reactivation. Patients should tell their doctor if they had hepatitis B virus or are a carrier of hepatitis B virus. Receiving Rituxan could cause the hepatitis B virus to become an active infection again. This may cause serious liver problems and death. People with active liver disease due to hepatitis B should stop receiving Rituxan.
• Heart problems. Patients should tell their doctor about any heart problems they have including chest pain (angina) and irregular heart beats. Rituxan can cause chest pain and irregular heart beats which may require treatment.
• Infections. Rituxan can increase the chances for getting infections. Patients should call their doctor right away if they have a cough that will not go away, fever, chills, congestion, or any flu-like symptoms while receiving Rituxan. These symptoms may be signs of a serious infection.
• Stomach and bowel problems. Serious stomach and bowel problems have been seen when Rituxan has been used with anti-cancer medicines in some patients with non-Hodgkin's lymphoma. Patients should call their doctor right away if they have any stomach area pain during treatment with Rituxan.

Common side effects during Rituxan infusions include fever, chills and shakes, itching, cough, throat irritation or tightness, headache, nausea, hives, and sneezing. Other side effects with Rituxan include aching joints, upper respiratory tract infection, decreased blood cell counts, and lung problems.

For additional safety information, please see the full prescribing information, including BOXED WARNINGS and Medication Guide, at 1-800-821-8590 or visit http://www.rituxan.com.