The considerable research into the sequencing of diffuse large B-cell lymphoma (DLBCL) has been led to important recent discoveries such as the recurrent mutations within histone modification and a number of new genetic targets. The panel discuss the potential for a more individualised targeted approach to DLBCL treatment but warn of the difficulties designing clinical trials for such small patient subgroups. Although clinicians are likely to be cautious before abandoning such a successful standard of care as R-CHOP, it is necessary to develop alternatives for patients known to have a poor prognosis with this agent.
A similar issue is faced in the treatment of Hodgkin’s lymphoma; any new therapies must be more effective than standard treatment with ABVD or escalated BEACOPP. These regimens are associated with cure rates of over 80%, but researchers are working to reduce toxicity for the 80% who can be successfully treated and to develop alternative agents for the 20% that cannot. Radiotherapy based therapies can be successful in the short term but are known to produce secondary leukaemias in the longer term. Markers to determine which patients will respond to particular treatments would allow doctors to avoid unnecessary secondary effects in patients that do not require dose escalation. The development of novel biological agents with low toxicity profiles is particularly important when considering lymphoma in the elderly. ABVD is highly toxic to these patents and it is hoped that the development of new drugs such as brentuximab vedotin (SGN-35), BTK or PI3K inhibitors will address this.
The panel talk about recent research showing that genetically modified T-cells can survive within a patient over a prolonged period of time. Although these results are extremely promising, the long term effects of such modifications to the immune system are not yet understood and the high associated cost is likely to prevent widespread use within the near future.