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Studies offer new insights into treatment of children, adolescents with Hodgkin lymphoma
Two Children’s Oncology Group studies suggest progress has been made in the treatment of and survival outcomes for children and adolescents with Hodgkin lymphoma.
Kara M. Kelly, MD, the Waldemar J. Kaminski endowed chair of pediatrics at Roswell Park Comprehensive Cancer Center, directed both studies through her role as chair of the Children’s Oncology Group (COG) Hodgkin Lymphoma Committee.
“Collaborative studies through this large network allow us to better understand factors affecting optimal delivery of care, as well as to identify how best to incorporate promising new targeted therapies,” Kelly told HemOnc Today.
In the first study, Kelly and colleagues sought to identify factors that contribute to survival disparities among children and adolescents with newly diagnosed Hodgkin lymphoma.
The researchers assessed 5-year EFS and OS among individuals with newly diagnosed Hodgkin lymphoma treated with contemporary, risk-adapted, response-based therapy on COG phase 3 trials.
“Our team observed no differences in survival by race or ethnicity, a finding of great significance for patients and their families,” Kelly said in a press release. “It suggests that the survival gap we have seen can be reduced by access to clinical trials, which allows delivery of comparable therapy to patients from all backgrounds.”
In the second study, Kelly and colleagues assessed the efficacy of a novel combination for children and adolescents with relapsed or refractory Hodgkin lymphoma. The regimen consisted of brentuximab vedotin (Adcetris, Seattle Genetics) — an antibody-drug conjugate that targets CD30, found on the surface of most classical Hodgkin lymphoma cells — and gemcitabine.
The researchers observed a significant decrease in serum thymus and activation-related chemokine after one cycle of treatment. Results showed increased rapid reduction in serum thymus and activation-related chemokine among those who achieved complete response but not among patients who did not achieve complete response.
“This is the first report demonstrating the usefulness of thymus and activation-related chemokine as a biomarker of treatment response specifically among children and young adults with Hodgkin lymphoma,” Kelly and colleagues wrote. “Future studies will test the value of altering retrieval strategy based on this early response marker.”
HemOnc Today spoke with Kelly about both studies and the implications of the results.
Question: What prompted this research?
Answer: For the outcomes study, historically across the age divide, there are barriers to trial participation for patients from racial and ethnic disparity groups. This is even more of a factor among young adults, the most common age group affected by Hodgkin lymphoma. As for the treatment study, the vast majority of cancer clinical trials are conducted through COG. I am the chair of COG’s Hodgkin lymphoma committee, and our overarching goals have been to improve treatment outcomes for high-risk patients, particularly those with relapsed disease. Given the younger population we work with, we are equally mindful about reducing the long-term toxic effects of our therapies. Data were emerging — primarily for adults — regarding the efficacy of brentuximab vedotin. This antibody is linked to a potent tubular toxin known as MMAE. Brentuximab vedotin has been associated with a 34% complete response rate and 76% overall response rate among patients with relapsed and refractory disease. For this reason, we were interested in combining the agent with other drugs and moving the agent earlier in the treatment process among pediatric patients with relapsed disease. The initial approval was for patients who relapsed after autologous stem cell transplant or multiple prior cycles of treatment for relapsed/refractory disease.
Q: What makes these studies unique?
A: What is different about the treatment study — led by Peter D. Cole, MD, associate professor of pediatrics at The Children’s Hospital at Montefiore — is that we combined brentuximab vedotin with gemcitabine. Gemcitabine also has single-agent activity, and the advantage of this combination compared with other combinations being tested for adults with Hodgkin lymphoma is that our combination does not have significant long-term toxicity. As for the outcomes study, we fortunately had good representation in our trial of all racial and ethnic groups, which has not always been the case in many previous trials.
Q: What did the findings suggest?
A: The treatment study was very successful. We set a bar of improving the response rate by at least 20% over our prior combination. Overall, we saw a complete response rate of 68% and overall response rate of almost 80%. This combination is highly active and has the advantage of not adding to the long-term complications often observed with these patients. Although this study did not have survival as a primary objective, the 1-year EFS was very high at 95%, and 34 of 45 eligible patients went on to high-dose chemotherapy with autologous stem cell transplant. For this very high-risk population of patients with Hodgkin lymphoma, these outcomes demonstrate the success of this new treatment regimen.
As for our outcomes analyses, although stage III/stage IV disease was more prevalent among black and Hispanic patients (P = .0002), no differences were observed in B symptoms or bulk by race or ethnicity. Additionally, we observed no differences in receipt of radiotherapy by race or ethnicity. Moreover, results of the pooled analysis showed that — at median follow-up of 6.9 years — 5–year EFS was 83% and 5-year OS was 97%. Neither outcome differed by race or ethnicity.
Q: What are the clinical implications of the findings?
A: What is most important about the brentuximab vedotin study is that we have identified an active combination treatment that can now be used for first-line treatment for patients with relapsed or refractory disease. The advantage is that it does not have the cumulative exposure to alkylating agents as other more commonly used combinations do, so risks for infertility and second cancers may be reduced. Another advantage is that this combination can be given in the outpatient setting, so this is more desirable to patients rather than having to be admitted to the hospital for administration of cancer treatment.
As for our outcomes findings, historically — across the age divide — there are barriers to trial participation for patients from disparate racial and ethnic groups. This is even more of a factor among the young adult group, which is the most common age group affected by Hodgkin lymphoma. Specifically, within pediatrics, there are fewer problems with access to clinical trials compared with some of the adult clinical trial groups. Fortunately, we had good representation in our trial of all racial and ethnic groups. Our data suggest that, if you provide good therapy through access to clinical trials, the differences between racial and ethnic groups are no longer present.
Q: What practical suggestions can you offer about how to overcome barriers to clinical trial participation ?
A: For our outcomes trial, this was less of an issue. However, other work I am involved in aims to better understand the reasons for these disparities. I am collaborating with the Lymphoma Research Foundation to be able to better understand the risk factors for this. We are comparing outcomes across different racial, ethnic and age groups treated on a series of COG trials for Hodgkin lymphoma to try to see if we can tease out which patients are at risk. We are then comparing this to an analysis we are doing with data from the New York State Cancer Registry and linked to Medicaid claims data to determine whether the issue is trying to get patients into clinical trials or if the issue is about the biological difference between racial, ethnic or age groups. This will help us to better understand which way future research should go.
Q: Is there anything else that you would like to mention?
A: In the field of Hodgkin lymphoma, there is a lot of interest and excitement about the incorporation of targeted agents rather than the more conventional cytotoxic chemotherapy. Building on our combination treatment regimen trial, we have opened another trial looking at the efficacy of this therapy in combination with immunotherapy. This is a regimen that is completely devoid of conventional cytotoxic chemotherapy and, therefore, should reduce even further the long-term toxicities of the treatment. This is a very exciting trial for us. It is the first time we are conducting a trial with our colleagues in Europe and the first time we are conducting a trial with no conventional cytotoxic chemotherapy. – by Jennifer Southall
References:
Cole PD, et al. Abstract 624. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.
Kahn JM, et al. Abstract 607. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.
For more information:
Kara M. Kelly, MD, can be reached at Roswell Park Comprehensive Cancer Center, Elm and Carlton streets, Buffalo, NY 14263; email: kara.kelly@roswellpark.org
Disclosure: Kelly reports no relevant financial disclosures.