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Clinical trials are currently exploring the application and frontline utilization of novel therapeutic approaches for the treatment of patients with Hodgkin lymphoma.
Targeting CD30 with the antibody drug conjugate brentuximab vedotin has greatly impacted the systemic treatment of Hodgkin lymphoma, believes Jonathan W. Friedberg, MD. This approach results in a response rate of nearly 80% with some durable remissions, in the salvage setting. This high-level of activity will likely alter the role of allogeneic transplantation in this setting, believes Friedberg. In addition to this initial indication, trials are exploring brentuximab vedotin in earlier lines of treatment, explains Friedberg. In a phase III trial, the standard regimen of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) is being compared to AVD plus brentuximab vedotin as a frontline treatment.
The HDAC inhibitor panobinostat was investigated at the same time as brentuximab vedotin, explains Craig H. Moskowitz, MD. In these separate studies, complete and overall response rate was shown to be much higher with brentuximab vedotin, leading to its FDA approval. However, Moskowitz adds, despite being less efficacious in these parallel trials, there still could be a role for HDAC inhibitors in Hodgkin lymphoma.
Agents that target the PI3K/AKT/mTOR pathway have shown promise in the treatment of patients with relapsed and refractory Hodgkin lymphoma, explains Lauren C. Pinter-Brown, MD. For instance, she notes, the mTOR inhibitor everolimus elicited a 40% response rate with prolonged disease control following autologous transplantation. Additionally, the safety and efficacy of the agent idelalisib (GS-1101), a PI3K delta inhibitor, is being explored in phase II trials.
Bendamustine and lenalidomide have shown promise in other hematologic malignancies, warranting their research in Hodgkin lymphoma, notes Paul A. Hamlin, MD. At this point, bendamustine has been explored as a treatment for patients who do not respond to salvage therapy. Unfortunately, this agent did not demonstrate a high-duration of disease control, Hamlin notes. Additionally, the immunomodulatory agent lenalidomide demonstrated activity in the last-line setting, Hamlin notes. However, further research is still needed to cull out which patients benefited the most.
While many of these novel agents are showing promising activity, it remains unclear where they will fit in the sequence, since 90% to 95% of patients with Hodgkin lymphoma are cured by ABVD, Friedberg adds. These agents will likely be incorporated into the treatment regimens of high-risk patients first, Friedberg believes. However, he adds, they may not ever make their way into standard regimens.