Pediatric Patients with CGvHD Ibrutinib OK'd by FDA

Pediatric Patients with CGvHD Ibrutinib OK'd by FDA

Gauri Sunkersett, MD, speaks about the FDA approval of Ibrutinib for cGvHD

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Pediatric Patients with CGvHD Ibrutinib OK'd by FDA


Chronic graft versus host disease, or CGvHD, is a condition associated with immune dysregulation that can occur about 100 days post an allogeneic stem cell transplant.


It is multisystemic. It usually occurs in the skin, the liver, the GI tract, the eyes, and the lungs so that it can be all-encompassing.


It is the leading cause of non-relapse mortality, and it is generally associated with delayed immune reconstitution, as well as infections. In the pediatric world, it can have a lower incidence versus the adult world.


However, the sequela and the morbidity can be much more detrimental because it occurs at a lower age, and these pediatric patients have the potential for a longer lifespan.


Imbruvica (Ibrutinib) is a first-in-class, potent, orally administered inhibitor of Bruton's tyrosine kinase BTK. So Imbruvica (Ibrutinib) works by inhibiting the signal transaction from the B cell receptor, and it primarily blocks B cell activation.

So in the literature, it has been well described that Alloreactive B Cells have been implicated in the development of CGvHD patients (chronic graft versus host disease).


Moreover, these activated B cells can produce a variety of inflammatory cytokines, as well as antigen presentation by autoreactive B cells is also critical in autoimmune disorders.

So CGvHD (chronic graft versus host disease) has been associated with dysfunction in these B cells. Imbruvica (Ibrutinib) is one of the most comprehensively studied BTK inhibitors, with over 150 active clinical trials in several blood cancers and other severe disorders.



This trial is the first pediatric approval for the AbbVie oncology portfolio Imbruvica (Ibrutinib) received by the US FDA (approval) on August 24th as the pryor (systemic) treatment for one year and older pediatric patients with CGvHD (chronic graft versus host disease, with moderate or severe CGvHD) after the failure of 1 or more lines of systemic therapy.


This approval also includes oral suspension formulation for Imbruvica (Ibrutinib) designed for the pediatric patient population CGvHD, for children. Furthermore, this approval is based primarily on our positive results from our phase 1/2 iMAGINE clinical trials. So this is huge news.


What Was The Response Rate or Median Duration In Children with Chronic GvHD?

So the iMAGINE study is a phase 1/2 trial sponsored by Pharmacyclics. It was an interventional single-group treatment study that evaluated the use of Imbruvica (Ibrutinib) in pediatric patients with CGvHD from 1 to less than 22 years of age with moderate to severe disease.


It is an open-label multi-center international phase 1 to dose-finding safety and efficacy study of oral Imbruvica (Ibrutinib) in pediatric patient population with CGvHD (chronic graft versus host disease) with moderate to severe disease. The study was divided into 2 parts. Part A was dose-finding and safety, and part B was PK safety and efficacy.


The results showed an overall response (rate or risk factors) through week 25 of 60% of pediatric patients (not adult patients) with a median age of 13 years ranging from 1 to 19 years old was relapse refractory monitor to severe pediatric patients with CGvHD.


So one of the key things I think was critical in this study is the safety surrounding Imbruvica (Ibrutinib including an oral suspension formulation).


So the safety was consistent with the established profile for Imbruvica (Ibrutinib) with observed adverse events consistent with those observed in moderate to severe adult CGvHD (in pediatric and adult patients?).


Adverse events are common with any drug that we utilize within this study. The most common AEs and those classified by those occurring in 20% or less of patients included laboratory abnormalities, such as anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, dermatitis, thrombocytopenia, as well as headaches.


Moreover, that is something that, as a study team, we wanted to investigate. So one of our exploratory objectives of the iMAGINE trial is to evaluate the change in the quality of life of pediatric patients with CGvHD (chronic graft versus host disease) during (initial) treatment with Imbruvica (Ibrutinib) as assessed by this standard theatric stem cell quality of life questionnaire.


The first FDA-approved treatment option after the failure of steroids for patients under 12 years of age. Thus, we offer newfound hope for a patient population with limited options otherwise.


So these patients will be monitored for growth and development, immune constitution, and late effects for up to 5 years post-enrollment.


As we previously mentioned, the current standard of care for CGvHD (chronic graft versus host disease) is corticosteroids, a significant immunosuppressant. Imbruvica (Ibrutinib including an oral suspension formulation) was the first approved treatment following the failure of one or more lines of systemic therapy in adults (in adult patients).


Furthermore, now bringing, this therapy to pediatric patients, especially those under 12 years of age, who otherwise did not have an approved treatment option. This truly offers an alternative option that has shown proven clinical benefit.


So Imbruvica (Ibrutinib, including an oral suspension formulation) is now the only BTKi with 12 approvals across 7 indications, including 5 hematologic cancers and CGvHD. It is a tremendous milestone within the pediatric oncology community. I am a pediatric oncologist.


I am also a mother. So I understand from so many different facets the importance behind this FDA approval. This provides hope for our providers, our caregivers, and our patients to finally have an approved therapy and an oral suspension within the pediatric population.


Gauri Sunkersett, MD - About The Author, Credentials, and Affiliations

She has specialized training in bone marrow transplantation and cellular therapeutics, and she specializes in pediatric hematology and oncology. Currently, she is looking for career opportunities that will allow her to advance these respective fields while maintaining her commitment to research and academia.


Cancer immunotherapy, cancer research, and gene therapy are all areas in which Dr. Sunkersett has a proven track record in the clinic as well as in the scientific literature.