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.
Splitting her time between the main Cornell campus in Ithaca and the Weill Cornell Medical campus in New York City, Dr. Kristy Richards has developed a unique plan to research new lymphoma treatments. Lymphoma is a common form of cancer in humans and also the most common form of cancer found in dogs. So as human oncologist, Dr. Richards thought that treatments for canine patients could lead to advances in the treatment of human lymphoma patients,
“Dog and human lymphoma patients share many biological similarities, as well as the unfortunate fact that rates of the disease are rising for both species. “We don’t know why this is,” Richards says. “It could be something in the environment, which both dogs and humans share. So in a way, dogs could be a canary in the coal mine.”
“Richards plans to test cutting-edge approaches such as immunotherapy, which harnesses the body’s natural defenses to fight off cancer cells, in dogs suffering from lymphoma. This September, she was awarded a supplement grant from the National Cancer Institute, in partnership with the Roswell Park Cancer Institute in Buffalo, to further explore canine immunotherapy with veterinary patients that come to the Cornell University Hospital for Animals.”
The full article can be read here. More information about Dr. Richards work and the practical benefits so far accrued for both two and four legged lymphoma patients can be found in the below video.
By Peter Martin, M.D.
Recently researchers from the Mayo Clinic presented data at the 2016 ASCO annual meeting suggesting that clinical trial participation might be associated with a survival benefit. The researchers used the Mayo Clinic Lymphoma Database to identify patients with relapsed Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), or relapsed mantle cell lymphoma (MCL), and compared the characteristics and outcomes of those enrolled in clinical trials versus those who were eligible, but not enrolled in clinical trials. Between January 2001 and December 2014, 340 patients with DLBCL, 159 with MCL, and 115 patients with HL were identified. Over this same period 47 unique Phase 1-3 trials led to the FDA approval of 17 treatments.
94 of 340 (27%) DLBCL, 63 of 159 (41%) MCL and 66 of 115 (57%) HL patients were enrolled on a clinical trial at some point during therapy, with 38% of patients enrolled in more than 1 study. Researchers found that the median survival of patients treated in a clinical trial was roughly twice as long as patients not treated on a clinical trial in all 3 lymphoma subtypes. There are several possible sources of bias or confounding that might explain the difference, despite the researchers’ efforts to control for these variables. Clearly, more research in this areas is indicated. Nonetheless, the magnitude of benefit was striking and should be reassuring to patients considering clinical trial participation.