Link Lends Insight on Progress, Challenges in Pediatric Cancer

Michael Link, MD

The cure rate for pediatric cancer, particularly acute lymphoblastic leukemia (ALL), have increased to approximately 90% in recent years. Moreover, encouraging phase III data suggest more therapeutic developments are occurring in this space.

In the AALL0434 trial, the addition of nelarabine to escalating-dose methotrexate (C-MTX) induced a 4-year disease-free survival (DFS) rate of 91% in a cohort of pediatric and young adult patients with newly diagnosed T-cell ALL or T-cell lymphoblastic lymphoma (T-LL).

The study included 3 other treatment arms comprising C-MTX alone, high-dose MTX (HD-MTX) alone, or HD-MTX plus nelarabine. All patients initially received the COG augmented Berlin-Frankfurt-Munster (aBFM) multidrug chemotherapy regimen.

The 4-year overall survival rate was 90.2% and the 4-year event-free survival rate was 84.1% for the 1545 evaluable patients.

However, Michael Link, MD, a 2018 Giant of Cancer Care^® in Pediatric Oncology, said there are still significant improvements to be made.

OncLive: How has the field of pediatric oncology evolved in recent years?

In an interview with OncLive, Link, Lydia J. Lee Professor in Pediatric Cancer, professor, Pediatrics, Stanford Cancer Institute, discussed the exciting progress being made for various pediatric tumors.Link: During my career, there has been phenomenal progress in the management of pediatric cancers. We now cure about 80% of children with this disease. In some diseases, such as ALL, it's closer to being between 90% and 95%. Looking back, when I started my fellowship, many of these diseases were incurable. For leukemia, perhaps 30% to 40% of children were cured. Now, we cure the overwhelming majority.

What are some milestones throughout your career that stand out?

Are there any recently presented studies that you find to be practice changing?

Burkitt lymphoma, a disease which I have an interest in, was incurable for everyone. Now, we cure with impunity—even patients with very advanced lymphoma. It's been a sea change and a wonderful time to be part of that tremendous improvement. The idea that we moved through incremental advances in clinical trials with these huge improvements in outcomes has been wonderful to see. Of course, these patients and their families that you devote your time to become part of your life. They are survivors. You realize some of the accomplishments that you were part of were disseminated elsewhere. You also see it in your own patients. You have a local impact, which is the most satisfying. However, also knowing you had an impact on someone else's life is a great feeling. One of the clear practice-changing studies is the addition of a new drug for the management of T-cell leukemia. This is a disease that, early on in my career, was most difficult to treat. We made very little progress early on—sort of hovering around curing 30% of children. With the advent of using the same drug, we managed to boost the outcome for these children to almost the same as other children with leukemia. We're still looking for those incremental changes that will continue to improve outcomes.

What are the next steps that need to be taken in pediatric oncology?

This study showed the addition of nelarabine, which is a relatively new drug, into already intensive treatment has improved outcome. That has been the story of pediatric oncology. It's been a series of steps. Over the years, it's resulted in this dramatic improvement in outcomes. There are several tumors where we haven't made this kind of progress. Brain tumors and central nervous system tumors are still a frontier where we need new answers. Patients who present with metastatic solid tumors are generally resistant to therapy. Neuroblastoma is a common tumor in toddlers.

Is there anything else you would like to add?

Unfortunately, despite very intensive treatments, we haven't been able to move the needle far. We have a long way to go there. The most exciting progressions have been the immunotherapies, especially the CAR T cells. The idea that you can demonstrate manipulating a patient's own immune cells result in dramatic improvements is very impressive. This therapy is now being moved upfront. It's been a game-changer. We as oncologists build on our predecessors and mentors. They have done much of the slugging away and bushwhacking through in developing therapies. One of the things that I hope I've done is encouraged my own trainees and mentees. I hope they also take away the importance of caring for individual patients from me. These families are going through a difficult time, but their bravery in participating in clinical trials is what has gotten us this far.

Dunsmore KP, Winter S, Devidas M, et al. COG AALL0434: a randomized trial testing nelarabine in newly diagnosed t-cell malignancy. J Clin Oncol. 2017(suppl; abstr 10500).