Imbruvica and Beyond: 4 Chronic Graft-vs.-Host Disease Medications Worth Considering

A bone marrow transplant, or stem cell transplant, is like a double-edged sword. It’s a lifesaving treatment for many blood conditions that were previously incurable. But there are potential health complications. For many, the chance for a cure is worth the risks.

One potential complication is graft-versus-host disease (GvHD). GvHD happens when your transplanted blood cells attack your body by mistake.

One form of GvHD — chronic GvHD — happens at least 3 months after your transplant. It can affect different parts of your body, including your eyes, skin, and mouth. Treatment includes medications that calm your immune system, including corticosteroids like prednisone. But when steroids aren’t enough, you’ll need other options.

Here, we’ll discuss chronic GvHD medications beyond steroids. Your transplant specialist will make the final call on if any of these medications are right for you.

1. Imbruvica

Imbruvica (ibrutinib) is an oral medication called a BTK inhibitor. BTK is a protein that’s involved in activating certain cells in the immune system. Imbruvica shuts off the BTK protein to suppress the immune system. This helps prevent newly transplanted cells from attacking healthy cells in your body.

Imbruvica is FDA approved for use in adults and kids ages 1 year and older. It’s used when at least one other chronic GvHD treatment hasn’t been successful. In a clinical study, Imbruvica improved chronic GvHD symptoms in two-thirds of people taking it. What’s more, over 70% of those people were able to keep symptoms well managed for at least 5 months.

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Imbruvica is convenient because you take it only once a day. And you don’t have to take it with food. It’s available in tablets and capsules, but it’s simpler to take the tablets. (Because of how they’re made, you’ll likely need to take only 1 tablet per dose. This is compared with 3 capsules per dose.) An oral suspension is also available for kids.

But side effects are sometimes a concern. If you have a history of abnormal heartbeats, Imbruvica may not be the best medication. In rare cases, Imbruvica may cause an abnormal heart rhythm called atrial fibrillation. Imbruvica can also increase your risk of bleeding. Other side effects of Imbruvica include pneumonia, diarrhea, and fatigue.

2. Rezurock

Rezurock (belumosudil) is another oral medication for chronic GvHD. But it works differently than Imbruvica does. It’s a ROCK2 inhibitor.

ROCK2 proteins normally activate certain cells in your immune system. But when ROCK2 is too active, it can worsen chronic GvHD. It increases the activity of immune cells that cause inflammation. This eventually leads to scarring of your inner organs (fibrosis). Rezurock turns off ROCK2 signals and helps decrease inflammation and fibrosis. This is a unique feature of Rezurock. Other oral chronic GvHD medications lessen inflammation but not fibrosis.

Rezurock is approved to treat chronic GvHD in adults and children ages 12 and older. Unlike Imbruvica, it’s prescribed to people who have failed at least two treatments. In a clinical study, Rezurock improved chronic GvHD symptoms in roughly three out of four people. Rezurock was able to keep symptoms at bay for about 1 year (and longer in some people).

Rezurock is also convenient — you have to take only 1 tablet daily. But you have to take it with food. This may be challenging for those with low appetite or an irregular eating schedule.

The side effects of Rezurock are similar to other medications that suppress the immune system. These include infections, high blood pressure, and high blood glucose. Other side effects include nausea, diarrhea, and fatigue.

3. Jakafi

Jakafi (ruxolitinib) is another oral chronic GvHD medication. It’s called a JAK1/JAK2 inhibitor. JAK proteins help promote parts of the immune system, including inflammation-provoking cytokines. Jakafi shuts off JAK signals, resulting in less inflammation.

Jakafi is approved to treat chronic GvHD in adults and children ages 12 and older. It’s used in people who have failed one or two previous treatments. In a clinical study, about half of people taking Jakafi saw an improvement in their symptoms. Other common treatment options improved symptoms in about a quarter of people.

Jakafi is typically taken twice daily. This is more frequent than Imbruvica and Rezurock, but it doesn’t have to be taken with food. The most common Jakafi side effect is low blood counts. Low platelets, white blood cells, and red blood cells can increase the risk of bleeding, infection, and excessive tiredness, respectively.

4. Niktimvo

Niktimvo (axatilimab-csfr) is an injectable medication for chronic GvHD. First approved in August 2024, it’s a CSF-1R-blocking monoclonal antibody. It fights back against another pathway in chronic GvHD that contributes to inflammation and fibrosis.

Niktimvo is approved to treat chronic GvHD in adults and kids who weigh at least 40 kg (88 lbs). It’s an option for those who haven’t found luck with at least two other treatments. In a clinical study, Niktimvo improved chronic GvHD symptoms within 6 months for about 3 out of 4 people who received it. More than half of these same people maintained this response for at least a year.

Compared to other chronic GvHD medications, Niktimvo is administered less frequently. It’s administered into a vein (IV) once every 2 weeks. The downside is that you’ll likely need to receive doses at a medical facility — not at home.

The most common Niktimvo side effects are infection, muscle pain, and changes to your lab work. Infusion-related reactions are also possible. The staff at your infusion center should help you monitor and respond to side effects like these.

Off-label medications for chronic graft-vs.-host disease

Three medications are approved for chronic GvHD. But many more are prescribed off-label by transplant specialists. Your transplant team may recommend one or more of them based on their experience and current supporting medical evidence.

Extracorporeal photopheresis

Extracorporeal photopheresis (ECP) is not a medication. But it’s a common procedure for people with chronic GvHD.

During ECP, your blood is collected in a machine. It’s treated with a chemical that makes white blood cells sensitive to light. Light is then shined on your blood as a form of treatment and infused back to you.

ECP is effective and has minimal side effects. But logistics make it unappealing to some people. You have to be willing to have a tube in your vein for a long time. You have to visit a medical office frequently for treatment (up to 2 to 3 days weekly). And the process can take 1 to 4 hours.

Orencia

Orencia (abatacept) is a costimulation modulator that’s approved to prevent acute GvHD. But it’s sometimes used for chronic GvHD. It blocks the activation of important immune cells, including T cells and cytokines.

Orencia is given IV every 2 weeks for a month, then once a month thereafter. Common side effects include infection, tiredness, and headache.

Proleukin

Proleukin (aldesleukin) simulates a naturally-occurring cytokine that promotes the activation of protective immune cells. For chronic GvHD, it may be given as a daily injection under the skin. The most common side effects include injection site reactions and flu-like symptoms.

Rituxan (and biosimilars)

Rituxan (rituximab) is a monoclonal antibody that targets a protein called CD20 on B cells from your immune system. Destroying B cells helps suppress the immune system.

In most chronic GvHD studies, Rituxan is given as a weekly IV infusion. The most common side effects are infusion reactions and infections.

Others

Additional off-label medications for chronic GvHD include: 

• Campath (alemtuzumab)

• Enbrel (etanercept)

• Low-dose methotrexate

• Calcineurin inhibitors like Prograf (tacrolimus)

• mTOR inhibitors like Rapamune (sirolimus)

• CellCept (mycophenolate mofetil)

• Nipent (pentostatin)

• Gleevec (imatinib)

• Plaquenil (hydroxychloroquine)

Good to know: Once you exhaust your FDA-approved treatment options for chronic GvHD, your responses to off-label treatments will likely be lower. Only about a quarter of people are thought to respond to many of these off-label options.

How to choose the best chronic graft-vs.-host disease medication

There are different options for chronic GvHD. But one isn’t widely considered better than the rest.

To choose the best medication for you, your transplant team will consider side effects, which organs your chronic GvHD is affecting, and previous medications you’ve tried. Treatment logistics and insurance coverage are also important; many of these treatments may have a high out-of-pocket cost.

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Written by:

Rachel Feaster, PharmD, BCOP, BCPS

Rachel Feaster has over 10 years of professional experience in ambulatory, inpatient, pharmacogenomics, and oncology care. She is board certified in oncology and pharmacotherapy.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Patricia Pinto-Garcia, MD, MPH

Patricia Pinto-Garcia, MD, MPH, is a medical editor at GoodRx. She is a licensed, board-certified pediatrician with more than a decade of experience in academic medicine.

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