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COMy 2020 | Myeloma XI trial: areas for further research

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Graham Jackson

Graham Jackson, MBBS, FRCP, FRCPath, MD, Newcastle upon Tyne Hospitals NHS Trust, Newcastle, UK, discusses lenalidomide as maintenance therapy in the Myeloma XI trial (NCT01554852). Results show that in young, fit, transplant eligible patients, lenalidomide prolongs progression-free survival. In patients who progress very early after transplant, some with high-risk cytogenetics do not respond well. However, a few patients also do not respond well despite normal cytogenetics. This could be due to extramedullary disease or circulating plasma cells at presentation, but further research is required. Lastly, patients are at high risk of venous thromboembolism despite being on the appropriate thromboprophylaxis. This interview took place during the Controversies in Multiple Myeloma (COMy) 2020 Virtual World Congress.

Transcript (edited for clarity)

Myeloma XI has asked a number of questions. We have shown both, particularly in younger fitter patients, that Revlimid maintenance prolonged progression-free survival and overall survival. One of the big pieces of data to come out of Myeloma XI is in the support of Revlimid maintenance as a treatment strategy for young transplant eligible patients. We’ve also shown that Revlimid maintenance doesn’t impact on clonal evolution, and the incidence of secondary, primary malignancies in that population is really very low...

Myeloma XI has asked a number of questions. We have shown both, particularly in younger fitter patients, that Revlimid maintenance prolonged progression-free survival and overall survival. One of the big pieces of data to come out of Myeloma XI is in the support of Revlimid maintenance as a treatment strategy for young transplant eligible patients. We’ve also shown that Revlimid maintenance doesn’t impact on clonal evolution, and the incidence of secondary, primary malignancies in that population is really very low.

Some of the other things to come out of Myeloma XI, recently, are one of the groups of patients who’ve drilled down on, where there is a big area of unmet need is in the patients who progressed very early after a stem cell transplant. That group of patients who’ve progressed within 12 months of a stem cell transplant, we’ve looked at them very, very closely. It is clear that whilst that population is enriched for high-risk cytogenetics, and is particularly enriched for patients with double and triple hit cytogenetic abnormalities. There are still some patients who do very badly in terms of a very short progression-free survival, who have standard-risk cytogenetics.

We need to ask, why is that? Do they have evidence of extramedullary disease, circulating plasma cells at presentation? But there are some patients who do badly. We still don’t have a great handle on why that is the case. We have shown in those patients who relapsed early after a stem cell transplant that their prognosis is really poor. Their PFS2 is 14 months shorter than the patients who don’t progress early, and their overall survival of three years is only 25%. We’ve really defined a high-risk group of patients there. I think the other thing that we’ve published very recently is around venous thromboembolic disease. This remains a significant cause of morbidity in myeloma patients. We have looked at all of the patients on Myeloma XI, and there is still a considerable thrombotic rate of around about 10% across treatment groups. That’s despite most patients getting appropriate thromboprophylaxis. I think one of the things we’ve definitely signaled is that thromboprophylaxis is still not perfect, and VTE is still a significant cause of morbidity for our patients.

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