JULIET: What the Lymphoma Trial Found

The short version

JULIET tested a treatment called tisagenlecleucel in adults with diffuse large B-cell lymphoma. Everyone in the trial had already run out of standard options.

Of the 93 people who received an infusion, 52% had their tumors shrink a lot or vanish. There was no comparison group. So the number cannot be read as proof that this beats other care. The report appeared in the New England Journal of Medicine in 2019. Novartis paid for the trial.

The cancer behind the trial

Diffuse large B-cell lymphoma, or DLBCL, is a cancer of B cells. B cells are white blood cells that normally make antibodies to fight infection. In DLBCL they grow out of control and build up in lymph nodes and other organs.

DLBCL is the most common fast-growing lymphoma in adults. SEER, the federal cancer surveillance program, counts about 5.6 new cases per 100,000 people each year in the United States.

Doctors call it "aggressive," meaning it grows fast and needs treatment soon. That is not the same as untreatable. Fast-growing lymphomas often answer well to chemotherapy.

How it is found

A diagnosis needs a biopsy. When possible a surgeon takes out a whole lymph node, because the pattern of cells across the node is part of the answer. A pathologist then studies the tissue and runs protein stains to confirm that the cells are B cells.

Staging uses the Ann Arbor system. It counts how many groups of nodes are involved, and whether the disease sits on both sides of the diaphragm. Scans are usually a PET-CT: a sugar tracer lights up busy cells, and the CT adds detail. Many people also have a bone marrow sample taken. Our guide to cancer staging walks through those numbers.

First treatment, and what comes after

Most people start with a mix of chemotherapy drugs plus rituximab. Rituximab is an antibody that latches onto CD20, a protein on the surface of B cells. It is given as infusions over several months, and it cures most people who get it.

When it fails, the usual next step is more chemotherapy and then an autologous stem-cell transplant. Autologous means the person's own blood stem cells are collected, frozen, and given back after very high doses of chemotherapy. Some people are too unwell for that. Others relapse anyway. Those two groups are exactly who JULIET enrolled.

What CAR T-cell therapy involves

CAR stands for chimeric antigen receptor. The team collects T cells, the immune system's attack cells, from the person's blood. A laboratory adds a gene so those T cells grow a new receptor on their surface. The receptor grips CD19, a protein carried by B cells, including cancerous ones.

The edited cells are grown into large numbers and shipped back. Before the infusion the person gets lymphodepleting chemotherapy, which clears room for the new cells. Then the cells go in once, and they keep multiplying inside the body. Our explainer on CAR T-cell therapy covers the schedule and the monitoring in more detail.

JULIET's real contribution was logistics. The cells were made at one central plant and shipped worldwide, rather than grown at each treating hospital.

The numbers

Among the 93 people assessed, 52% responded. The 95% confidence interval ran from 41% to 62%. A confidence interval is the range the true figure most likely sits in.

Of that group, 40% had a complete response, meaning no cancer could be detected. Another 12% had a partial response. Among people who responded at all, an estimated 65% were still free of relapse a year later. Among those with a complete response, that figure was 79%. The median time from infusion to the data cutoff was 14 months.

Side effects were serious

Severe or life-threatening events included:

• Cytokine release syndrome in 22%. This is a whole-body immune overreaction with high fever and falling blood pressure.
• Nervous system events in 12%, such as confusion or trouble speaking.
• Low blood counts lasting more than 28 days in 32%.
• Infections in 20%.
• Fever with low white cells in 14%.

Three people died of their lymphoma within 30 days of the infusion. The authors linked no deaths to the therapy itself.

The wider survival picture

SEER reports that 64.8% of people diagnosed with DLBCL between 2016 and 2022 were alive five years later. Broken out by stage at diagnosis, the figures were 79.9% for stage I, 76.0% for stage II, 67.5% for stage III, and 56.3% for stage IV.

Read those as group averages. They pool thousands of people of every age and health state, and cover years when CAR T-cell therapy was rare. They describe a population, not any one reader.

When to get a swollen node checked

A lump that shows up with a cold usually settles within a couple of weeks. Ask a clinician to look if:

• A node stays swollen more than three or four weeks, or keeps growing.
• The lump is painless, firm, and bigger than about 1 inch (2.5 cm).
• You soak nightclothes or bedding with sweat.
• You run fevers above 100.4°F (38°C) with no infection to explain them.
• You have lost more than a tenth of your body weight in six months without trying.

The last three are known as B symptoms, and they feed into the stage a doctor assigns.

What this trial cannot tell you

• There was no control group. Nobody in JULIET received a different treatment for comparison, so the 52% cannot be measured against what chemotherapy would have done in the same people.
• Roughly half of those treated did not respond at all.
• The denominator is 93 people who were infused. Anyone enrolled whose cells were never made or never given is outside that count, which flatters the percentage.
• Follow-up ran to a median of 14 months. Long-term cure rates were unknown at this report.
• The toxicity needs a center staffed and equipped for it. Nearly a quarter had severe cytokine release syndrome.
• Trial entry criteria are narrow, so these results may not carry over to everyone with this diagnosis. Trial phases explains what a phase 2 study is designed to settle.

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• Schuster SJ and colleagues, "Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma," New England Journal of Medicine, 2019 (PMID 30501490): https://pubmed.ncbi.nlm.nih.gov/30501490/
• SEER Cancer Stat Facts, Diffuse Large B-Cell Lymphoma: https://seer.cancer.gov/statfacts/html/dlbcl.html
• National Cancer Institute, Non-Hodgkin Lymphoma Treatment (PDQ), patient version: https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq

How this page was made

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.

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