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.
Last week the Mayo Clinic received an $11 million grant from the National Cancer Institute (NCI) to support research addressing the current and long-term unmet healthcare needs of patients with non-Hodgkin lymphoma. This NCI funded, multi-institutional project is known as the “Lymphoma Epidemiology of Outcomes Cohort Study”. At the Weill Cornell site, Dr. Peter Martin will serve as the Principal Investigator, and Dr. John Leonard will be a participating investigator.
As Principal Investigator at the Weill Cornell site, Dr. Martin, who is the Charles, Lillian, and Betty Neuwirth Clinical Scholar in Oncology, will be overseeing the recruitment of participants and reporting of outcomes. “The LEO Collaboration will be the largest study of it’s kind anywhere in the world and will undoubtedly lead to important, impactful discoveries. We look forward to enrolling participants at Weill Cornell as we seek avenues to increase long-term prognosis and survivorship for those living with NHL,” says Dr. Martin.
Working with participating investigators, Dr. John Leonard and Dr. Giorgio Inghirami (Pathology, Weill Cornell Medical College). “This multi-institutional collaborative study group, supported by the NCI, has a highly productive track record. We are very happy to be a part of it,” says Dr. Leonard.
Look to this space for further information about this study, and other Hodgkin lymphoma related trials. A full listing of our non-Hodgkin lymphoma trials can be found here.
The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with diffuse large B-cell lymphoma. The study sponsor is Acerta Pharma BV, and the principal investigator at Weill Cornell is Dr. Jia Ruan. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at firstname.lastname@example.org.
- Men and women greater than or equal to 18 years of age
- Confirmed de novo ABC DLBCL, and subjects must have archival tissue available for central pathology review
- Recurrence of disease after a complete response or progressive disease at the completion of the treatment regimen preceding entry to the study
- Detailed eligibility will be reviewed when you contact the study team
The purpose of this study is to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of ACP-196 in treating subjects relapsed or refractory de novo ABC diffuse large B-cell lymphoma (DLBCL).
Clinical Studies have shown that targeting the B-cell receptor (BCR) signaling pathway by inhibiting Bruton tyrosine kinase (Btk) produces significant clinical benefit in patients with non-Hodgkin lymphoma. Acerta Pharma BV has developed a novel second generation Btk inhibitor, ACP-196, that achieves significant oral bioavailability and potency.
This study is a multi-center, open-label, randomized, parallel group study. No placebo will be administered during this study. Twenty subjects, 10 refractory and 10 relapsed, will be enrolled and will take 100 mg of ACP-196 twice per day.
Treatment will occur for 5 cycles with a 30 day follow-up period following the last dose. Treatment with ACP-196 may be continued for more than 28 days until disease progression or an unacceptable drug-related toxicity occurs. Subjects with disease progression will be removed from the study. All subjects who discontinue study drug will have a safety follow-up visit 30 (±7) days after the last dose of study drug unless they have started another cancer therapy within that time frame.