FDA Approves First-Ever Targeted Marginal Zone Lymphoma Treatment

On January 19, 2017, the United States Food and Drug Administration (FDA) approved ibrutinib to treat patients that have received at least one line of prior therapy for marginal zone lymphoma (MZL), a type of non-Hodgkin lymphoma (NHL).

MZL is an indolent B-cell lymphoma that accounts for 5-10% of all lymphomas and lacks a standard of care. Current MZL treatments include anti-CD-20 antibody therapy (e.g. rituximab) or chemotherapy. However, ibrutinib is the first-ever treatment to specifically be approved for MZL.

Ibrutinib works by inhibiting Bruton’s tyrosine kinase (BTK), an enzyme responsible for transmitting pro-growth and survival signals from the surface of a cell to its nucleus. In this way, ibrutinib may interfere with chronic stimulation arising from inflammation in the tumor microenvironment; thus slowing the growth of B-cells.

The Weill Cornell Lymphoma Program is proud to have played a role in the phase 2 trial — the largest trial to date for people with previously treated MZL of all subtypes —leading to FDA approval for ibrutinib. Roughly half of all patients had a significant response to ibrutinib, with some degree of tumor shrinkage observed in almost 80% of all patients in the trial. Roughly one-third remained on treatment 18 months after beginning treatment.

The most common side effects included fatigue, diarrhea, and anemia. These side effects were manageable, and consistent with previous research, although some cases required the discontinuation of treatment with ibrutinib.

Results from this study support the use of ibrutinib as an effective well tolerated chemotherapy-free option for the treatment of previously treated MZL. However, some questions remain. MZL is a heterogeneous group of lymphomas, and it is unclear which subtypes might respond best to ibrutinib. With only half of all previously treated MZL patients responding to ibrutinib, improvements might be realized by combining ibrutinib with other drugs and/or using it earlier in the treatment of MZL.

At Weill Cornell, we are currently studying ibrutinib in combination with the immunotherapy drug durvalumab in people with previously treated indolent non-Hodgkin lymphoma, including MZL.

Weill Cornell Breakthrough Research: Shutting Down DLBCL Master Protein; Potential for New Treatments

Reporting in Nature Immunology, Weill Cornell’s Dr. Ari Melnick and his research team have reported an important research breakthrough in diffuse large-B cell lymphoma (DLBCL) that may offer hope for new treatments for aggressive lymphomas.

Dr. Melnick has found that it is possible to shut down the protein Bcl6, a powerful master regulatory transcription factor that is the key to survival for many aggressive lymphomas arising from the B-cells.

“The finding comes as a very welcome surprise,” says the study’s lead investigator, Dr. Ari Melnick, Gebroe Family Professor of Hematology/Oncology and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell.

The protein Bcl6 was previously considered too complex to target with individual drugs, because of its centrality in the functioning of the body’s healthy immune cells.

“This means the drugs we have developed against Bcl6 are more likely to be significantly less toxic and safer for patients with this cancer than we realized,” says Dr. Melnick.

DLBCL is the most common subtype of non-Hodgkin lymphoma — the seventh most frequently diagnosed cancer, with many patients resistant to currently available treatments. Presently, there are ongoing clinical trials for those suffering from non-Hodgkin’s lymphoma and other forms of lymphoma at the Weill Cornell Lymphoma Center.

The full press release can be read here.