FDA Approves Expanded Use of Ibrutinib for Chronic GVHD

Ibrutinib, a BTK inhibitor commonly used to treat lymphoma types like chronic lymphocytic leukemia (CLL) and mantle cell lymphoma, has been approved by the United States Food and Drug Administration (FDA) for treatment of adults with chronic graft versus host disease (cGVHD).

Ibrutinib Pills in Hand

GVHD can occur following a stem cell or bone marrow transplant from a related or unrelated donor, also known as an allogeneic transplant. When the immune cells from the graft (donor) are infused into the body of the host (patient), they may recognize the host’s native cells as foreign and try to destroy them. While some cases of GVHD are life threatening, chronic cases tend to generate to more mild symptoms, like dry eyes and mouth, fatigue, and muscle weakness and stiffness.

Ibrutinib becomes the first FDA-approved treatment of cGVHD following clinical trials demonstrating durable safety and effectiveness in patients whose symptoms were resistant to prior corticosteroid treatment administered for immune system suppression.

Dr. Richard Furman Examines Future of CLL Risk Assessment

At OncLive’s State of the Science Summit on Hematologic Malignancies, Dr. Richard Furman, director of the Chronic Lymphocytic Leukemia (CLL) Research Center at Weill Cornell Medicine, discussed how medical oncologists should be using prognostic markers to make risk assessments in order to determine individualized treatments for their patients with CLL.

SOSS_Richard_FurmanDr. Furman noted that current CLL therapies are effective, but they often lead to complications. CLL patients treated with standard chemotherapy drug combination fludarabine, cyclophosphamide, rituximab (FCR) are often prone to developing treatment resistance or Richter’s transformations (RT), in which their CLL transforms into a more aggressive diffuse large B-cell lymphoma (DLBCL). They may also succumb to infectious complications, adverse events, or secondary malignancies.

Because of the risks associated with FCR treatment, Dr. Furman suggested a movement toward treatment agents that are not as toxic, such as ibrutinib. But even with ibrutinib, patients can develop resistance to treatment. For example, in cysteine481-to-serine mutations, the amino acid in Bruton’s tyrosine kinase (BTK) that ibrutinib binds to is changed from a cysteine to a serine, prohibiting ibrutinib from continuing to bind. This results in inadequate ibrutinib coverage and enables CLL cells to escape treatment and survive.

According to Dr. Furman, a large number of CLL patients will have excellent responses and enjoy very long progression free survivals. What is important is to identify those who will not and to devise a treatment strategy that can improve their outcomes. Currently, interphase FISH (demonstrating deletion 11q or 17p), NOTCH1 mutation, or certain V genes help identify those patients who will progress on currently novel agents or have a risk of Richter’s transformation. In the future, stimulated karyotyping, or evaluating changes in the chromosomes after stimulation of the CLL cells, will also be of great importance.

The CLL team at Weill Cornell Medicine and NewYork-Presbyterian is currently investigating an early intervention trial in which patients at risk of developing Richter’s transformation or resistance to BTK inhibitors receive intervention before the mutations have a chance to develop. Our team is also looking into the use of combination therapies, such as ibrutinib and venetoclax, in treatment of CLL patients.

Additionally, Dr. Furman pointed out that prognostic markers are dependent upon the setting in which they’re used. Those used for FCR, such as minimal residual disease (MRD), don’t necessarily apply to ibrutinib. He said that prognostic markers are traditionally based upon responses, but we now need to start looking at them from a progression-free survival (PFS) perspective.

To hear more from Dr. Furman about the outlook of CLL prognostic markers, check out this short OncLive clip:

Dr. Peter Martin’s Manuscript Selected as Top 10 Manuscript for 2016

Earlier today the editors of Blood, the journal of the American Society of Hematology selected the top 10 most outstanding manuscripts of 2016. Dr. Peter Martin was the first author in one of the selected abstracts titled ‘Post Ibrutinib outcomes in patients with mantle cell lymphoma‘. (MCL)

Dr. Peter Martin
Dr. Peter Martin

Dr. Martin led a team of researchers at Weill Cornell Medicine and centers from around the world in a retrospective study of patients with MCL who experienced disease progression while receiving ibrutinib. These researchers found that MCL patients who progressed during treatment with ibrutinib have a poor outcome. As there are no therapies that appear to be uniquely successful in the post-ibrutinib setting this represents an unmet need.

You can read about the full results from their study in the abstract.

Congratulations Dr. Martin!