XXXX : Optimal Therapy for MYC-positive, Double-Hit, and Triple-Hit @entity1892 .

@entity632 @entity1 @entity588 @entity706 @entity229 @entity3726 @entity786 @entity2109 @entity4042 @entity1892 @entity1891
OPINION STATEMENT: Approximately 10  % of cases of @entity1892 ( @entity1892 ) harbor a MYC rearrangement and this has been associated with an inferior outcome following standard therapy across many different studies. Double-hit and triple-hit @entity706 harbor concurrent rearrangements of MYC and @entity588 and/or @entity4042 and are also associated with a very aggressive course and poor clinical outcome. It is unclear and there is lack of consensus on how these diseases should be approached therapeutically. They are characterized typically by high tumor proliferation and likely require @entity2109 -type strategies and several retrospective studies suggest that more intensive approaches than rituximab, @entity786 , @entity632 , @entity1891 , and @entity229 (R- @entity3726 ) may be beneficial. One challenge in this respect is that most @entity1 with these diseases are older than 60  years and generally have poor tolerability of regimens typically used in @entity2109 . Dose-adjusted EPOCH-R is an alternative effective immunochemotherapy platform for @entity1892 and is effective in @entity2109 , and retrospective studies suggest that it is effective and feasible in @entity1 with @entity1892 that harbors a MYC rearrangement with or without a @entity588 translocation (double-hit). A multicenter study of this approach in MYC-rearranged @entity1892 is ongoing and preliminary results are very encouraging. There is a lack of consensus on the role of consolidation stem cell transplantation in @entity1 who achieve a good response to initial therapy but at this point in time, no (retrospective) studies have demonstrated any benefit. These diseases are also associated with a high rate of CNS involvement and progression and checking for cerebrospinal fluid by cytology and flow cytometry at initial diagnosis should be considered. In summary, based on retrospective data and preliminary prospective data (as more mature data is awaited), while Burkitt-type regimens may be feasible in young @entity1 , DA-EPOCH-R is a reasonable approach for @entity1 with these diseases, particularly for those over the age of 60  years. CNS prophylaxis is a reasonable consideration (depending on clinical characteristics) given that the rate of CNS progression is high. Many exciting new small molecule inhibitors such as @entity588 and MYC inhibitors are in development and are exciting for these diseases and attempts are underway to combine them with effective immunochemotherapy platforms.
