A trial looking at ibrutinib and rituximab for post-transplant lymphoproliferative disorder (TIDaL)

Cancer type:

Blood cancers

Lymphoma

Secondary cancers

Status:

Results

Phase:

Phase 2

This trial looked at adding ibrutinib to rituximab to treat post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder can develop after:

a stem cell transplant . This is a treatment for some types of cancer.
an organ transplant such as the heart, lung or liver

The trial was open for people to join between 2017 and 2020. The team published the results in 2024.

More about this trial

Post-transplant lymphoproliferative disorder (PTLD) are lymphomas Open a glossary item . They can develop in people who are having treatment to damp down their immune system after a transplant. PTLD happens because the immune system isn’t working well. So a type of white blood cell called B cells might grow out of control. Sometimes these cells might change into cancer cells if they are not treated.

When this trial was done, the first treatment for PTLD was rituximab. It is a targeted cancer drug Open a glossary item . It works for some people but most also need to have chemotherapy. The standard chemotherapy at the time of this trial was CHOP chemotherapy. The combination of rituximab and CHOP chemotherapy is called R-CHOP.

R-CHOP works but it can cause an increased risk of infection, damage to organs in the body and additional side effects. So doctors were looking for newer ways to treat PTLD.

In this trial they looked at a targeted cancer drug called ibrutinib. They knew from research that it worked for some other types of blood cancer. So they thought it might help people with PTLD.

There were 2 stages to this trial. In stage one, everyone had ibrutinib and rituximab as their initial treatment. After 7 weeks, the researchers looked at how well this had worked.

In stage 2, people had treatment depending on how the initial treatment had worked:

if it had worked well, they continued to have ibrutinib and rituximab (low risk group)
if it hadn’t worked well, they had ibrutinib and R-CHOP (high risk group)

The main aims of this phase 2 trial were to find out:

how well ibrutinib and rituximab work as initial treatment
if adding ibrutinib to rituximab improves treatment for low risk patients
if adding ibrutinib to R-CHOP improves treatment for high risk patients
what the side effects are

Summary of results

42 people who had post-transplant lymphoproliferative disorder (PTLD) joined the trial. Of those 39 had treatment.

Results for stage one
After 7 weeks of ibrutinib and rituximab, everyone had a scan to see how the treatment worked. The team looked at whose PTLD had gone away completely. They found this was 12 people. This is about the same as having rituximab on its own.

Results for stage two
Everyone was then put into 1 of 2 groups. This depended on how well the treatment in stage one had worked:

16 people had ibrutinib and rituximab (low risk group). In this group their initial treatment had worked well. So they needed less intensive treatment to stop the lymphoma from coming back.
23 people had ibrutinib and R-CHOP (high risk group). In this group their initial treatment didn’t work well. So they needed more intensive treatment to stop the lymphoma from coming back.

At the end of treatment, the team looked at the total number of people whose PTLD had either gone away or shrunk. This was:

13 out of 16 people (81%) in the low risk group
13 out of 23 people (57%) in the high risk group

The team say that adding ibrutinib to the existing treatment plan for PTLD didn’t work any better.

Side effects
Most people who took part in this trial had at least 1 side effect. Some side effects were mild, but others were more severe.

23 people (59%) had side effects that were more severe.

The most common severe side effect during initial ibrutinib and rituximab treatment was tummy pain.

The most common severe side effect of further ibrutinib and rituximab was a drop in the number of white blood cells called neutrophils Open a glossary item .

The most common severe side effects of ibrutinib and R-CHOP were:

a drop in the number of red blood cells (anaemia )
a drop in the number of white blood cells called neutrophils and a high temperature
a drop in the number of neutrophils
tummy pain
diarrhoea
being sick
sepsis
a low level of phosphate in the blood
numbness and tingling in the hands or feet
low blood pressure

2 people died because of the side effects of treatment. Both were in the group having ibrutinib and R-CHOP.

We have more information about the side effects of R-CHOP and ibrutinib in our Cancer drugs section.

Conclusion
In this small trial, the team found that adding ibrutinib to initial rituximab wasn’t a useful treatment for PTLD. The team say it didn’t work well enough to look at in a larger trial.

They also say that the risk of side effects from CHOP chemotherapy means that other treatments are urgently needed. More trials need to be done looking at newer treatments for PTLD. This is to reduce the side effects of treatment and increase the length of time people live.

Sometimes trials show that a different treatment isn’t useful. These trials still add to our knowledge and understanding of cancer and how to treat it.

More detailed information
There is more information about this research in the reference below.

Please note, the information we link to here is not in plain English. It has been written for healthcare professionals and researchers.

Ibrutinib as part of risk-stratified treatment for posttransplant lymphoproliferative disorder: the phase 2 TIDaL trial
S Chaganti and others
Blood, 2024. Volume 144, issue 4, pages 392–401.

Where this information comes from
We have based this summary on the information in the article above. This has been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in a medical journal. We have not analysed the data ourselves. As far as we are aware, the link we list above is active and the article is free and available to view.