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.
Click on the graphic above to watch this interview from the 2016 annual meeting of the American Society of Hematology, Lymphoma Program Director, Dr. John Leonard discusses results from the recently completed GALLIUM trial. In this trial researchers compared the safety and efficacy of either rituximab or obinutuzumab with chemotherapy followed by maintenance with the same agent as first-line therapy for patients with previously untreated follicular lymphoma.
By John Allan M.D.
The survival of tumor cells is dependent on the tumor cells maintaining a normal interaction with the healthy microenvironment. An increasingly important strategy in the treatment of CLL is to develop new therapies that do not necessarily attack the cancerous cells themselves, but instead attack the molecular processes that allow the cancerous cells to function and thrive in the microenvironment. One potential target for treating CLL is the protein complex NF-kB, which controls important cell functions including the regulation of cell death, cell survival, and cell proliferation. If NF- kB function can be inhibited then CLL can be more easily treated.
The purpose of this recent study presented at the 2016 ASH meeting was to test the efficacy of the newly developed NF-bK inhibitor IT901 in the treatment of CLL and its aggressive transformation Richter’s Syndrome (RS). RS is a transformation that occurs within 5-10% of CLL’s and turns the disease into a fast growing diffuse large B-cell lymphoma, an aggressive non-Hodgkin lymphoma. The treatment of RS currently represents an unmet therapeutic need.
Results from this study were confirmed in a mouse xenograft model for people with CLL and in cell samples obtained from people with RS. In both models the use of IT901 was characterized by decrease in tumor growth and Researchers found that IT901 induced death in cancerous cells within 24 hours of treatment with a minimal impact on normal B-cells.
Researchers concluded that IT901 is effective in rapidly blocking NF-kB activity by decreasing the functions that allow the cell to flourish in the microenvironment. The results from this study are encouraging and point to a potential new treatment option for patients with CLL and RS.