Patients who relapse early could be considered high risk.Poor responders to treatment are considered high risk.Having a combination intermediate risk abnormalities.In summary, he noted that the following was considered high risk myeloma: He then ranked the value, showing the del(17p) mutation was the most high risk feature. As you can see in the chart, having a trisomy of 5 was beneficial. He then presented a model to rank the risk of these features. The patient relapsed within 18 months and had 100% of cells with the 1q gain, suggesting that testing for genetic features at diagnosis and again at relapse was important. The patient was treated with Velcade/Revlimid/dex as induction therapy and another genetic test was performed showing the 1q gain at 70% of cells. He showed a chart of a myeloma patient who had very little 1q gain (16%) at diagnosis. He said that having any amount of 1q gain can be important. It is frequently found with other myeloma genetic mutations such as t(4 14) and del(17p). It can be a high risk feature and has a median survival of 5 years. The 1q gain is found in 35% of myeloma patients, making it a more common feature. There were no recent studies using new therapies for patients with this feature. The discussion on del(1p32) was short and he simply noted that 8-10% of patients have this mutations and it has a median survival of 2 years. He doesn't believe t(14 16) should stay in the definition of high risk. In a 2018 study from ASH on 213 patients (the largest study to date), the median survival was 88 months (7.3 years). He noted that this was not the case in the IFM/DFCI 2009 study. He questioned whether it was an independent factor in prognosis. Aveg-Loiseau shared that t(14 16) was a translocation found early in a myeloma diagnosis, and it was only found in 3.5% of myeloma patients. He said additional work was being done to see if there were related breakpoint locations at chromosome 4, but that work was early. It is frequently associated with a del(17p), a del(1p32) or plasma cell leukemia. He believes that alone, it is not a high risk feature. He asked then, how we should dissect high risk in the t(4 14) patients? He believes that alone, it is not necessarily a high risk feature. He noted that the t(4 14) was very heterogeneous, with patients having a variety of both good and poor outcomes. He noted that in the past, the median survival was 5 years, but he is seeing patients live longer. Translocation of 4 14ĭr. Avet-Loiseau then described the t(4 14) patients which encompass 11-15% of all myeloma. He showed a patient who started with the del(17p) mutation and then acquired the TP53 mutation at relapse. Avet-Loiseau suggested that genetic testing was needed both at diagnosis and at relapses. Should these mutations be identified and followed only at diagnosis? Dr. Patients who had the TP53 mutation in addition to del(17p) had worse outcomes with an average 36 month survival compared to those without the TP53 mutation with 52.8 month survival (see chart below). Avet-Louiseau also reviewed if having only del(17p) was equally high risk to patients who also had the TP53 mutation in addition to the del(17p). The European group did research on more than 1,000 del(17p) patients and found that patients who have more than 55% of del(17p) in their plasma cells are high risk while those who have less than 55% of del(17p) are not high risk. However, we know from the MMRF COMPASS study that patients who have only one 17 chromosome missing behave as standard risk patients while those missing both 17 chromosomes behave as high risk. Del(17p)įor the last 20 years, the deletion of 17p has been thought to be high risk. The changes represent an evolution in thinking based on greater experience and research. At the International Myeloma Workshop in Vienna, French researcher Herve Avet-Louiseu, MD, PhD shared a presentation about how he sees high risk myeloma today and into 2022.
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