What Is Opdivo, and Why Does It Matter?
Opdivo (nivolumab) is an immunotherapy medication approved to treat a broad range of cancers. The FDA has now approved Opdivo to be used in combination with AVD chemotherapy (doxorubicin, vinblastine, and dacarbazine) for previously untreated stage III-IV classical Hodgkin lymphoma (cHL) in adults and adolescents aged 12 and older.
Additionally, the FDA granted full (traditional) approval to Opdivo for adults whose cHL has come back (relapsed) or who did not get help from prior treatments (refractory), specifically for those who have undergone a stem cell transplant and received brentuximab vedotin or who have received at least three different types of treatments, including a stem cell transplant. Initially, based on early promising results, Opdivo was granted accelerated approval for these uses. However, as later studies confirmed its benefit, Opdivo has now been granted full approval.
cHL is the most common form of Hodgkin lymphoma, making up about 95% of all cases. The cancer most often affects young adults and usually begins with painless swelling in the lymph nodes in areas like the neck. A key feature of this disease is the presence of abnormal cells called Reed-Sternberg cells surrounded by other immune cells. Generally, cHL has a high cure rate with proper treatment.
Opdivo is a lab‑made antibody that works by selectively blocking programmed death receptor 1 (PD‑1), a protein located on the surface of T cells (immune cells), which otherwise helps cancer cells hide from the immune system. By turning off this immune checkpoint, Opdivo helps your immune system find and attack cancer cells. In AVD chemotherapy, doxorubicin and dacarbazine damage the DNA of cancer cells, and vinblastine prevents them from dividing and multiplying. Thus, the three medicines work together to block the growth and spread of tumor cells.
This approval matters because Opdivo-combined AVD chemotherapy offers an early and effective immune-based treatment option that may help improve outcomes in patients with previously untreated advanced stage III or IV cHL. First approved in 2014, Opdivo is approved to treat a range of cancers, including melanoma; lung, kidney, liver, bladder, head and neck, stomach, esophageal, and colorectal cancers; and cHL.
Why Was It Approved?
This FDA approval is based on data from a clinical study that showed that the combination of Opdivo with chemotherapy helped patients 12 and older with previously untreated stage III or IV cHL live longer without their cancer getting worse compared with the standard treatment.
The clinical study assessed how well Opdivo worked when combined with AVD chemotherapy in 994 patients 12 and older with newly diagnosed advanced stage III or IV cHL. Patients were randomly assigned to receive either Opdivo plus AVD chemotherapy or brentuximab vedotin combined with AVD chemotherapy for six treatment cycles.
The main goal was to see how long patients lived without their cancer getting worse (called progression-free survival or PFS). The results showed that the Opdivo group did better, with a hazard ratio of 0.42, meaning patients had a 58% lower risk of their disease getting worse compared with the other treatment group. After a median of 13.7 months of follow-up, the median PFS was not reached in either group, suggesting a durable benefit. After a median of 36.7 months, death rates were low in both groups: 1.8% in the Opdivo plus AVD group and 3.4% in the brentuximab vedotin plus AVD group.
Side effects reflected what is already known about Opdivo in combination chemotherapy. In the Opdivo plus AVD group, the most common side effects were nausea, vomiting, constipation, mouth sores, fatigue, muscle or joint pain, anemia, low counts of white blood cells (leukopenia) and neutrophils (neutropenia), a feeling of tingling “pins and needles” and numbness (peripheral neuropathy), and elevated levels of liver enzymes (transaminases).
What Do I Need to Know?
You or your child will receive Opdivo intravenously with AVD on days 1 and 15 during a 28‑day cycle for up to six cycles. If you weigh 40 kilograms (88 pounds) or more, you will receive a specific dose; if you weigh less than 40 kg, dosing is based on your body weight. On infusion days, Opdivo is given after the AVD medicines, and each Opdivo infusion takes about 30 minutes. If you miss a dose, call your health care provider at the earliest opportunity to reschedule your appointment.
Your health care provider may start preventive treatment with granulocyte colony‑stimulating factor (G‑CSF) with the first cycle to reduce your or your child’s risk of having low counts of white blood cells.
Opdivo can cause the immune system to attack healthy organs anywhere in the body, affecting their function. These immune‑related side effects can be mild, severe, or rarely fatal and may occur during or after treatment. Hence, your health care provider will regularly check you or your child for early signs of these complications and may pause or stop treatment, depending on how serious the side effect is. Serious problems have happened in people who received a donor stem cell transplant (allogeneic hematopoietic stem cell transplantation) either before or after Opdivo treatment. If this applies to you or your child, your care team will monitor you closely and weigh benefits and risks. Your health care provider will also guide you on how to watch for signs and symptoms depending on the organ or tissue transplant that you or your child has received.
Before taking Opdivo, tell your health care provider if you or your child has conditions that affect the immune system such as Crohn’s disease, ulcerative colitis, or lupus; if you have had an organ, tissue (including a corneal transplant), or stem cell transplant; if you or your child have received radiation to the chest or medicines similar to Opdivo; or if you have any nerve or muscle conditions such as myasthenia gravis or Guillain-Barré syndrome. Be sure to let your health care provider know about all details related to your or your child’s medical history, including any lung, liver, kidney, hormonal, heart, or skin problems.
Be sure to let your provider know if you are pregnant or planning to become pregnant as Opdivo can harm a fetus. Use effective birth control and do not breastfeed during treatment and for five months after the last dose.
Call your health care provider right away if you or your child develops new or worsening symptoms such as trouble breathing; diarrhea or black, tarry, or sticky stools; yellowing of the skin or eyes; severe rash or blistering or peeling of the skin; eye or vision problems; unusual headaches; increased sweating; increased hunger or thirst; extreme tiredness; changes in mood or behavior such as irritability or forgetfulness; swelling in the ankles; reduced urine volume or blood in urine; or new nerve problems as these may be signs of serious side effects.