COG Addresses Unmet Needs in Pediatric NHL

Birte Wistinghausen, MD

To address the unmet need of pediatric patients with non-Hodgkin lymphoma (NHL) who do not experience event-free survival (EFS) after chemotherapy, investigators from the Children’s Oncology Group (COG) are currently exploring several targeted therapies.

One of the COG studies is ANHL12P1, which is evaluating chemotherapy in combination with brentuximab vedotin (Adcetris) or crizotinib (Xalkori). The trial will be in patients with newly diagnosed stage III/IV anaplastic large cell lymphoma (ALCL). This study is currently recruiting for the crizotinib arm, while the brentuximab vedotin arm has completed accrual.

Another study is ANHL1131, which is evaluating the safety and efficacy of rituximab (Rituxan) in children or adolescents with higher-risk NHL. This phase II/III trial is specifically for patients with B-cell lymphoma or B-cell leukemia, based on findings from an experience of adults with diffuse large B-cell lymphoma who were treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like chemotherapy.

OncLive: What is the interest with targeted therapies in the treatment of NHL?

What ongoing research with targeted therapies is there in this population?

Does any of the rationale for using targeted agents in pediatric patients with NHL come from what is being used in adults?

What has been the biggest challenge in creating targeted therapy trials for this population?

What take-home point would you like to make to oncologists about targeted therapies in pediatric NHL?

In an interview with OncLive^®, Birte Wistinghausen, MD, medical director of the Division of Pediatric Hematology-Oncology, the Kravis Children's Hospital and Icahn School of Medicine at Mount Sinai, and a member of the COG Non-Hodgkin Lymphoma Committee, shared her insight on the potential for targeted therapies in the treatment of pediatric NHL, and the steps that COG is taking to cure all patients with this disease.Wistinghausen: Within the NHL community, we have been committed to advancing targeted therapies for most of our pediatric lymphoma types. We think that we have reached the limit of what we can do with chemotherapy alone. Our cure rates are pretty favorable. Overall, children and adolescents diagnosed with NHL in the United States can expect an EFS rate approaching 90%. Further intensification of chemotherapy may lead to unexpected toxicities. Therefore, we would like to bring targeted therapies to the frontline setting, so that we can eventually reduce chemotherapy and the associated toxicities with that.Most of our frontline trials do include targeted therapies. We just completed the frontline trial for patients with mature B-cell lymphoma, which is a joint trial with the Europeans showing that rituximab led to a significant increase in EFS when added on top of chemotherapy. We have an open study for ALCL, which randomizes patients to either receive brentuximab vedotin or crizotinib in combination with a chemotherapy backbone. Both of those are different targeted therapies. Brentuximab vedotin is the anti-CD30 antibody, and ALCL expresses CD30. Crizotinib is an ALK inhibitor, and greater than 95% of pediatric ALCLs have ALK positivity.It does. Often, the adult world has access to these drugs much earlier than we do. However, it is often based on studies that were done by the COG Phase I Consortium. The Phase I Consortium is so important for the COG because they can [test] these drugs in a limited institution setting, and then move them very quickly to a group-wide setting. Since COG includes 219 institutions, and every single institution contributes a couple of patients, it is such a powerful setting to make sure that these drugs get streamlined through the development process, and [that these drugs] become available for every child in the United States with cancer.We obviously want to cure every child with cancer, but with our cure rates being so high with so few relapses, it is very hard to run a study on such a small patient population. That is one of our limitations. It forces us to develop intergroup trials, either with the Europeans or with the adult group, which is a concept currently in development for patients with primary mediastinal B-cell lymphoma. We are going to use pembrolizumab (Keytruda), which is an anti—PD-1 agent, together with chemotherapy. That trial will be open to both pediatric and adult patients.The take-home message is that our cure rates are good, but the work is not done. We believe that the only way to get the work done is to turn to targeted therapies, and that will take collaboration across institutions and groups. Hopefully, we can eventually reduce chemotherapy toxicity and exposure with targeted therapies.

Wistinghausen B. Targeted therapies in NHL. In: Proceedings from the 2018 ASPHO Conference; May 2-5, 2018; Pittsburgh, Pennsylvania. Abstract 2014.