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ASH 2018 HL Studies
ASH 2018: A Preview of Key Hodgkin Lymphoma Studies to be Presented in San Diego

Released: November 27, 2018

Expiration: November 26, 2019

Andrew M. Evens
Andrew M. Evens, DO, MSc, FACP
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The annual conference presented by the American Society of Hematology (ASH) is one of the leading scientific meetings in the fields of hematology and oncology. The 2018 conference will be held in San Diego, California, and data from numerous clinical studies of Hodgkin lymphoma management will be presented. As a clinician, here are some of the studies I am most excited about.

Initial Treatment for Early-Stage Favorable Hodgkin Lymphoma
At the 2018 ASH meeting, we will see final results of the phase III HD16 trial, in which patients with early-stage favorable Hodgkin lymphoma were randomized to combined-modality therapy with 2 cycles of ABVD plus radiotherapy vs 2 cycles of ABVD alone (N = 628; Abstract 925). As in previous studies such as EORTC H10 and RAPID, this study used PET scanning after 2 cycles of chemotherapy to evaluate whether response at this stage could predict individual outcomes and whether PET negativity might allow for the reduction of treatment intensity (ie, the omission of radiotherapy).

Preliminary results from this trial showed that there was an increased risk of relapse in patients not receiving 20 Gy of radiation. As reported in the abstract, at a median follow-up of 47 months, the 5-year PFS rate was 93.4% with combined therapy vs 86.1% with ABVD alone. For the goal of preservation of PFS, radiotherapy plus ABVD remains the optimal option for early-stage favorable Hodgkin lymphoma; however, this should continue to be balanced with the potential of late effects for individual patients.

Initial Therapy for Patients With Advanced Hodgkin Lymphoma
Older patients with Hodgkin lymphoma have historically had a markedly inferior outcome vs younger patients. There are multiple ongoing efforts to identify new treatment regimens for this population. My colleagues and I will present a subset analysis of patients aged 60 years or older who participated in the phase III ECHELON-1 study (Abstract 1618). In this analysis, 186 older patients with previously untreated stage III/IV Hodgkin lymphoma were randomized to brentuximab vedotin plus AVD vs ABVD. Of note, the 2‑year PFS rates (modified and not modified) were not different for these older patients with brentuximab vedotin plus AVD vs ABVD. Conversely, in patients younger than 60 years of age, both modified PFS and PFS were significantly improved with brentuximab vedotin plus AVD. We analyzed possible reasons for the similar PFS rates in older patients; unsurprisingly, older patients experienced more toxicity with both regimens than younger patients, with more more peripheral neuropathy and febrile neutropenia observed for all patients and more pulmonary events occurring in the ABVD arm.

Another study of interest comes from the German Hodgkin Study Group and the Nordic Lymphoma Group, who conducted a single-arm phase II trial of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (B-CAP) in elderly patients (older than 60 years of age) with newly diagnosed advanced-stage Hodgkin lymphoma (N = 49; Abstract 926). CAP is similar to CHOP chemotherapy but excludes vincristine. According to the abstract, the ORR with B-CAP was 98% for these patients and, at the end of therapy, the complete metabolic response was 65%. The PFS data will be presented at ASH.

In addition, we will see long-term follow-up data from the SWOG 0816 study of initial response‑adapted therapy for younger patients (younger than 60 years of age) with stage III/IV Hodgkin lymphoma (Abstract 929). In this study, all patients started with 2 cycles of ABVD followed by a PET scan. If the scan was positive, treatment was switched to escalated BEACOPP; if it was negative, the patients remained on ABVD. Results from the abstract showed that OS for patients in this study was very good: 94% remained alive at 5 years, and the 5-year PFS rate was 74%. Notably, however, in the PET‑negative group, nearly 25% of patients experienced relapse events. This suggests a possible limitation of response‑adapted therapy in advanced-stage disease regarding long-term PFS.

Findings from these and other recently published studies provide the rationale for a large North American randomized phase III clinical trial that is being actively planned and will compare brentuximab vedotin plus AVD to nivolumab plus AVD for patients with untreated advanced-stage Hodgkin lymphoma.

Treatment of Patients With Relapsed/Refractory Hodgkin Lymphoma
In the setting of transplantation-eligible relapsed/refractory Hodgkin lymphoma, salvage therapy has historically included multi-agent chemotherapy (eg, ICE, DHAP) followed by autologous stem cell transplantation. With the emergence of novel therapeutics in recent years, there is significant interest in evaluating targeted agents in patients with primary relapsed/refractory disease.

One presentation of interest at ASH 2018 will be the phase II CheckMate 744 study, a response-adapted, open-label clinical trial of nivolumab plus brentuximab vedotin for children, adolescents, and young adults (aged 5-30 years) with low-risk or standard-risk relapsed/refractory Hodgkin lymphoma (Abstract 927). Patients achieving a CR with this induction regimen proceeded immediately to high‑dose chemotherapy and stem cell transplantation, whereas patients who did not have a complete metabolic response received intensification with brentuximab vedotin plus bendamustine. As noted in the abstract, patients in the standard-risk cohort (n = 32) showed an encouraging initial complete metabolic response of 64% after induction therapy; these data validate similar findings from a phase I/II trial in adults with Hodgkin lymphoma. Of note, all 6 patients who received intensification achieved a complete metabolic response.

Also of note, preliminary results from the phase I/II ECOG‑ACRIN E4412 study will be presented. In this study, patients with relapsed/refractory Hodgkin lymphoma received a combination of 3 targeted agents: ipilimumab, nivolumab, and brentuximab vedotin (N = 22; Abstract 679). As described in the abstract, phase I results showed an ORR of 82%, with a CR rate of 68% and manageable toxicities. These findings support continuing with the larger randomized phase II study comparing the doublet of brentuximab vedotin and nivolumab with or without ipilimumab.

Most Hodgkin lymphomas strongly express CD30, yet the CAR T-cells brought to market thus far have been CD19-targeted agents for B-cell lymphomas. It is challenging to target CD30 in Hodgkin lymphoma in part because it is also expressed on T-cells. Nevertheless, 2 phase I/II feasibility studies of CD30-targeted CAR T-cell therapy for Hodgkin lymphoma are under way and will be presented at ASH 2018 (Abstracts 680 and 681). Overall, preliminary results from both of these small studies suggest that CD30 CAR T-cell therapy in Hodgkin lymphoma is not only feasible but may provide excellent antitumor activity in patients with relapsed/refractory disease.

Your Thoughts?
What presentations are you most looking forward to this year? Please share your thoughts by joining the conversation in the comments box below.

Going to be in San Diego? Register here to join me and my co-panelists Robert W. Chen, MD, and Joseph M. Connors, MD, FRCPC, for an exciting, case-based satellite symposium in which we will discuss current best practices and emerging strategies for managing patients with Hodgkin lymphoma. In addition, CCO will again provide Independent Conference Coverage of ASH 2018. As the ASH annual meeting unfolds, remember to check the CCO Web site often for downloadable slidesets summarizing key studies and then again after the meeting has adjourned for CME-certified online activities, featuring expert analyses and perspectives on the clinical implications of the data.

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Which of the following types of studies on Hodgkin lymphoma management are you most looking forward to from the ASH 2018 meeting?
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