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On Saturday 3rd December, during the 58th Annual Meeting & Exposition of the American Society of Hematology (ASH), in San Diego, CA, an educational session took place between 9.30am–11.00am, titled “Hodgkin Lymphoma: Treatment Today and the Challenge for Tomorrow.” This session was Chaired by Andrew Lister, MD, of Barts Cancer Institute, London, UK, and focused on how the outcome of patients with HL in 2016 can be improved, beyond that achieved in the last 50 years, with combination chemotherapy and extended-field megavoltage radiotherapy.
“Novel agents and strategies in transplant-eligible patients with relapsed and refractory Hodgkin Lymphoma” was the second talk during this session, and was presented by Craig H. Moskowitz, MD, from the Memorial Sloan Kettering Cancer Center.
Dr Moskowitz began his talk by explaining that out of 8,000 patients with HL, treatment will fail in approximately 1,400 patients.
A potential approach to treating R/R HL was then presented, however there are some issues with this:
Dr Moskowitz then made the point that the randomized studies we are conducting and writing now will not be reported for another 5 years. Drug development is moving very rapidly and so is approval of new agents; the era of the phase I-II-III paradigm needs to end. Phase III trials may have little impact on how patients are treated, a lesson learned from the AETHERA study.
In this study, only 10% of patients had one unfavorable prognostic factor of the five factors predicted for PFS:
There are a number of issues concerning the AETHERA study:
The two most important issues when evaluating patients for ASCT were then outlined:
Between 1994 and 2003, second-line therapy was risk-adapted based on the MSKCC 3 factor model: B-symptoms, extranodal disease, and relapse <1 year. Pre-transplant functional imaging was the most significant determinant of outcome. Currently, PET is used pre-ASCT and it has been shown to be consistently prognostic.
The next topic explored in this talk was salvage therapy, beginning with an overview of the current status:
Dr Moskowitz went on to recommend sequential therapy, and also explained why:
The talk then focused on checkpoint inhibitors, specifically PD-1 blockade. Currently, there are 75 prospective clinical trials open at MSKCC studying checkpoint inhibitors in solid and liquid tumors. In terms of mechanism, currently we know that PD-1 blockade releases inhibition on adaptive immunity in solid tumors:
However, is this how it works in HL? Probably not:
The current, overall experience with nivolumab and pembrolizumab was summarized:
Dr Moskowitz then posed the question “should all transplant-eligible patients undergo HDT/ASCT with the availability of CPI?”
It was then asked if we have forgotten about allogeneic stem cell transplantation in this new era of CPI. It was noted that CPI have not cured any patients with HL yet. There are issues with how allogeneic transplantation and CPIs work together in current and future practice:
Dr Moskowitz then shared results by Reid W. Merryman et al. who investigated the safety and efficacy of allogeneic hematopoietic stem cell transplant following PD-1 blockade in relapsed/refractory lymphoma.
Finally, Dr Moskowitz shared his current strategy, which is subject to change, for patients who fail ASCT:
The majority of patients with Hodgkin lymphoma are cured with frontline therapy; however, 10% to 15% with early-stage disease and 20% to 30% with advanced stage require second-line therapy that includes a potentially curative transplant, of which an additional 50% to 55% are cured. Those with multiply relapsed disease traditionally would receive novel agents on a clinical trial or combination chemotherapy as a potential bridge to an allogeneic stem cell transplant. This treatment paradigm has changed with the availability of brentuximab vedotin, an antibody drug conjugate used pre- and post-ASCT, as well as for palliation. With the availability of the checkpoint inhibitors, nivolumab and pembrolizumab, there will be another shift in treatment, with these agents being used for palliation and potentially replacing allogeneic stem cell transplantation in certain patient populations. Finally, up-front management is also changing and this will have an impact on how patients in the relapsed and refractory setting will be treated.
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