In this editorial, Andreas Engert, MD, makes the case for consolidation therapy in advanced Hodgkin lymphoma.
Dr Engert is a professor of internal medicine, hematology, and oncology at University Hospital of Cologne in Germany. He has received research funding and consultancy fees from Takeda/Millennium Pharmaceuticals and Affimed as well as research funding from Bristol-Myers Squibb.
Historically, Hodgkin lymphoma has been viewed as a cancer with generally favorable outcomes. However, it’s clear that there is an unmet need for patients with advanced stage disease.
Physicians treat newly diagnosed patients with a curative intent, but up to 30% fail to respond to initial therapy or relapse, depending on the treatment regimen used, stage of disease, and risk factors.1-3 Additionally, toxicity from frontline treatment has the potential to impact patients throughout their lives.
In line with the current standard of care, the majority of patients who fail frontline therapy will receive high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).
This path of treatment, similar to frontline regimens, can be effective in eradicating the disease, but approximately half of those who undergo an ASCT subsequently relapse. Outcomes are generally poor for patients whose disease returns post-ASCT, especially if the relapse occurs within the first year.4
Consolidation therapy, used to kill remaining cancer cells after ASCT, may offer a new treatment option to address this problem. Unlike longer-term maintenance therapy, consolidation typically lasts for a short period of time—normally months instead of years—and involves intense treatment to eradicate any remaining disease.
The evidence for consolidation therapy in Hodgkin lymphoma
To understand the rationale for consolidation therapy, first consider why some patients with Hodgkin lymphoma relapse following ASCT. A small number of cancer cells, undetectable using traditional diagnostics, may remain following ASCT. This is known as minimal residual disease, and it may indicate the potential for the cancer to return.
The goal of consolidation therapy is to eliminate minimal residual disease before it progresses and causes a relapse. Unsurprisingly, timing plays a crucial role in the likelihood of achieving that goal.
In order to allow for the best chance for optimal patient outcomes, consolidation treatment should be initiated shortly after ASCT, before regrowth of cancer cells can occur. Tolerability is paramount, though, and timing must be carefully weighed by the treating physician.
Physicians and researchers learned about the impact and use of consolidation therapy from its success in other blood cancers like chronic myeloid leukemia.5,6
To prove the concept of consolidation treatment in Hodgkin lymphoma, a controlled clinical trial was conducted. The AETHERA study evaluated the use of brentuximab vedotin as consolidation therapy in patients with advanced Hodgkin lymphoma who were at increased risk of relapse or progression following ASCT.7
AETHERA was the first completed phase 3 study to explore consolidation treatment immediately following ASCT as a way of extending the effect of transplant in patients with Hodgkin lymphoma.
The results made a strong argument in favor of consolidation therapy, as patients who received brentuximab vedotin plus best supportive care after ASCT lived significantly longer without their disease worsening versus those on the placebo regimen. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.
Based on these data, consolidation therapy with brentuximab vedotin has been approved in several countries as a treatment option for patients with Hodgkin lymphoma who are at increased risk for relapse or progression following ASCT.
An important next step: Treating the right patients at the right time
Translating clinical evidence into real-world practice, physicians must look at which patients are most likely to benefit from consolidation therapy following ASCT—namely, those who are at increased risk of relapse. The effort to identify clear risk factors for relapse is still in progress.
Researchers across the world are currently studying patient characteristics and outcomes to determine a definitive set of risk factors that can better illustrate which patients should receive consolidation treatment.
Examples of factors under consideration include the stage of disease at diagnosis, tumor size, time to relapse, and response to previous treatment.8 Experts generally agree, however, that increased risk is cumulative and that it is not clear that any one risk factor is more important than others.
As researchers work to answer outstanding questions about consolidation therapy, there are a number of actions that the Hodgkin lymphoma community can take to help bring the right treatment options to patients.
Existing guidelines need to be evaluated and, if appropriate, adapted to give physicians across the globe the information that will allow them to provide the best care for patients at increased risk of relapse following ASCT.
Hematologists and oncologists then have the responsibility to stay informed of revisions to guidelines and to practically apply the latest research of consolidation therapy into their clinical practices.
The possibility now exists to potentially cure some Hodgkin lymphoma patients within a group that has traditionally experienced poor outcomes. As a result, a new treatment paradigm in this setting is emerging—one that may help solve the challenge of post-ASCT relapse in Hodgkin lymphoma.
Additional information on the use of consolidation therapy in Hodgkin lymphoma is available in the paper, Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat?
1 Diehl, V, Franklin, J, Pfreundschuh, M, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin’s Disease. N Engl J Med 2003;348:2386-95.
2 Duggan, D, Petroni, G, Johnson, J, et al. Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin’s Disease: Report of an Intergroup Trial. J Clin Oncol 2003;21:607-614.
3 Federico, M, Luminari, S, Iannitto, E, et al. ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin’s Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805-811.
4 Arai S, Fanale M, deVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54:2531–2533.
5 Zonder, J and Schiffer, C. Update on practical aspects of the treatment of chronic myeloid leukemia with imatinib mesylate. Curr Hematol Malig Rep 2006;1:141.
6 Giralt SA, Arora M, Goldman JM, et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007;137(5):461-467.
7 Moskowitz CH, Nadamanee A, Masszi T, et al; for the AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853-1862.
8 Bröckelmann PJ, Müller H, Casasnovas O, et al. Risk factors and a prognostic score for progression free survival after treatment with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (rrHL). Poster presented at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.