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Study of t(11;14) translocation may offer ‘valuable real-world evidence’ to advance myeloma treatment
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The International Myeloma Foundation has collaborated with AbbVie on a retrospective chart review study to assess outcomes of patients with multiple myeloma who have t(11;14) translocation.
“There are significant knowledge gaps about multiple myeloma, and among these gaps is the role of genetic mutations in response to treatment and the related outcomes for patients,” Brian Durie, MD, chairman of International Myeloma Foundation, said in a press release. “This study has the potential to provide valuable real-world evidence that can help advance care for patients.”
The primary objective of the study is to determine OS for patients with multiple myeloma who have the t(11;14) translocation. Secondary outcomes include objective response rates, PFS, time to disease progression, time to next treatment, duration of response, and rates of OS associated with different treatment regimens.
HemOnc Today spoke with Durie about the study, the timeline for results, and how the findings may help guide myeloma diagnosis, management and treatment.
Question: What prompted this research?
Answer: We realized that this particular translocation in the myeloma cells, known as t(11;14) translocation, is linked to increased production of BCL-2, a protein within the myeloma cells that blocks apoptosis. The protein allows the myeloma to survive and resist many different types of therapy. It became quite important to know in what context this translocation occurs.
We had several initial questions, including what the normal occurrence and pattern of this t(11;14) translocation is, whether other translocations occur among these same patients, and what the natural history of myeloma is that has this t(11;14) translocation. We knew that approximately 20% of patients do have this particular translocation but, until now, what exactly happens to these patients from the time of diagnosis up until when they may need treatment for relapse has never been tracked.
Q: How prevalent is this translocation in myeloma and what is known a bout its impact?
A: We have known for a number of years that the presence of this is a good prognostic factor. In other words, patients with the t(11;14) translocation have longer remissions and live somewhat longer — as much as 3 years compared with patients who may have other translocations. Relatively speaking, the presence of the t(11;14) translocation is a good prognostic indicator.
Q: How will the study be conducted?
A: We have reached out to centers around the world that are diagnosing and treating myeloma. We have identified 30 to 40 centers that have a significant number of patients with the t(11;14) translocation. We anticipate being able to generate data on about 1,500 patients. We created an electronic data capture form that is sent to each center and asks for key information about each patient to help us understand how old they were when diagnosed, how they responded to their first therapy, how long the remission lasted and what happened with subsequent therapies. We also inquire about the existence of other translocations that could affect outcomes. The data are sent to our statistical team, which assess different aspects of diagnosis, response and outcome.
Q: What is the timeline for results?
A: We hope complete results will be published by early 2019.
Q: How do you hope the findings will guide the diagnosis, management and treatment of these patients and improve their outcomes?
A: The main thing we hope we will discover is whether patients with t(11;14) translocation are linked to good prognostic features. One good prognostic feature we are looking for is trisomy, which is when patients with myeloma have an extra chromosome. If this happens to be the case, it will tell us that the overall outcome will be good, and also that combining BCL-2 therapy with another therapy could be a good selection. Results could guide selection of a combination approach to therapy. Conversely, if we find that t(11;14) translocation can sometimes or often be linked to poorer prognostic features, then we would understand that — in those cases — we will need to be much more cautious with treatment if we expect to see good outcomes.
Q: Is there anything else that you would like to mention?
A: This is an example of precision medicine. We are trying to understand a specific translocation and then fine-tune a therapy against this specific translocation. We have learned that about 4% of patients with myeloma have a BRAF mutation. We have treatment for this, but patients tend to have a short-lived response. We hope that, by targeting the t(11;14) translocation, we will be able to get much stronger benefit in this targeted approach. – by Jennifer Southall
For more information:
Brian Durie, MD, can be reached at International Myeloma Foundation, 12650 Riverside Drive, Suite 206, North Hollywood, CA 91607.
Disclosure: Durie reports no relevant financial disclosures.