Advances in Pediatric Oncology

Dr. Lisa G. Roth

At NewYork-Presbyterian Weill Cornell Medical Center, cancer care goes far beyond diagnosis and treatment to meet the unique needs of adolescents and young adult (AYA) patients with lymphoma. “Focusing on AYAs is particularly relevant in lymphoma, which is the most common cancer diagnosis in young adults,” says Lisa G. Roth, MD, Pediatric Hematologist-Oncologist at NewYork-Presbyterian Weill Cornell Medical Center. “During this critical time of life, lymphoma patients have complex medical and psychosocial needs such as finishing their educations, living independently, preserving their fertility, and maintaining quality of life.”

“The AYA Lymphoma program addresses the specialized needs of these patients through a multidisciplinary collaboration of pediatric oncologists, medical oncologists, social workers, psychologists and fertility preservation specialists who work together to formulate an optimal and comprehensive plan of care tailored to the individual patient,” explains Dr. Roth, who serves as Director of the AYA Lymphoma Program. “Our three-pronged approach involves providing the highest level of clinical care; meeting their psychosocial needs through support networks; and advancing much-needed research of promising new therapies in this population through clinical trials and translational research that we are performing at Cornell.”

Dr. Roth brings her passion, training and her deeply personal experience to the AYA Lymphoma Program, which she launched in 2013 after she herself was diagnosed with Hodgkin lymphoma. “As a young adult, I remember going to the clinic for my treatments and feeling lost as I looked around and saw mostly much older people,” she says. “That feeling of being lost combined with the experience of having your whole world turned upside down, which is universal for cancer patients, gave me an entirely new perspective that spurred the creation of a dedicated program for young persons, ages 15 to 39, who are living with a lymphoma diagnosis. These patients can fall through the cracks, not quite fitting in at pediatric or adult treatment centers. They’re also more likely to be uninsured than are older adults, and they have to worry about distinct issues, like their future fertility.”

Infertility can be a side effect of life-saving lymphoma treatments such as chemotherapy and radiation. “For both men and women, lymphoma treatments can impact their ability to have children later in life, so it is very important for patients to address fertility before we even begin therapy,” explains Dr. Roth. “Fortunately, we are in a unique position to do this through our strong relationship with the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine (CRM) at NewYork-Presbyterian Weill Cornell Medical College. This team is internationally recognized for their state-of-the-art efforts in fertility preservation for cancer patients.”

“At the time of diagnosis and before therapy begins, the CRM fertility preservation team meets with patients to discuss specific risks of the treatment regimen and options for potentially preserving fertility in advance of therapy,” she explains. “Women who wish to retain their potential to have children in the future have the option of cryopreserving their eggs (oocytes) or fertilized eggs (embryos) for use in future pregnancies.”

Another important issue for AYA lymphoma patients is limiting the toxicity of their cancer treatment, as most are likely to live for many years beyond their lymphoma. “We select treatments through the lens that this is curative therapy for our patients’ long-term survival,” says Dr. Roth. “Hence, we keep a keen eye on limiting the immediate toxicity and also the long-term toxicity of their treatments, as we expect them to have many healthy years ahead.”

To address their psychosocial needs, the AYA Lymphoma Program offers a wide range of educational materials, support groups, and a dedicated AYA lymphoma social worker who has access to national lymphoma resources. “Our program enables our patients to meet other young lymphoma patients, share resources and derive comfort just from knowing that there are other people like them who are going through similar experiences,” says Dr. Roth.

Today, Dr. Roth is involved in research initiatives that explore the biology of lymphoma in teens and young adults, offering clinical trials that study the efficacy of new drugs with fewer side effects. “The AYA lymphoma field has not experienced the major advances that we have seen in other childhood cancers,” says Dr. Roth. “Our goal is to address the unique needs of this age group, both in terms of planning for a long, healthy life after treatment and also by finding more targeted therapies with fewer side effects.”

Dr. Roth is spearheading a national clinical trial to explore the efficacy of an immune checkpoint inhibitor in children and adults with primary mediastinal B-cell lymphoma (PMBCL), a fast-growing non-Hodgkin lymphoma.  “This subtype of lymphoma is not like other types of lymphomas because it specifically occurs in adolescents and young adults, with a peak incidence in young women,” explains Dr. Roth, who is Principal Investigator. “We are developing a randomized Phase 3 trial evaluating the addition of an immune checkpoint inhibitor to chemotherapy for patients with newly diagnosed PMBCL.  Our goal is to determine if this combination results in a superior, long-term progression free survival when compared with chemotherapy alone in patients with this lymphoma subtype.”

“What is so exciting is this is the first trial to explore a novel agent in both pediatric and adult patients with PMBCL,” says Dr. Roth. “We are glad to offer the opportunity for young PMBCL patients to have early access to a novel class of therapy, which we know has activity in the relapsed/refractory form of the disease.” The trial, which is planning to open for enrollment in late 2020, is a joint effort of the Children’s Oncology Group (COG), the Alliance for Clinical Trials in Oncology, and other cooperative groups in the National Clinical Trials Network of the National Cancer Institute.

In another study, Dr. Roth and her team will use a specialized technique to perform genomic sequencing of Hodgkin Reed-Sternberg (HRS) cells, the rare cancer-causing cells in Hodgkin lymphoma that represents less than 1% of a Hodgkin lymphoma tumor.

The findings will be used to develop the first mouse model of Hodgkin lymphoma to screen new therapies. “The standard method used to isolate HRS cells is tedious and yields an insufficient number of cells for genetic sequencing,” explains Dr. Roth. “However, because these cells can be identified by their large size and unique characteristics, we are able to isolate them from a tumor biopsy using flow cytometry, which separates HRS cells based on cell structure and specific proteins on their cell surface.”

“We are isolating Reed-Sternberg cells from 100 biopsies taken from U.S. patients and then performing genomic sequencing to discern their genetic compositions,” she continues. “The ultimate goal of this study is to develop novel targeted therapies for the treatment of Hodgkin lymphoma in children and young adults. More effective targeted drug therapies may not only prolong the survival of children affected by Hodgkin lymphoma, but may also reduce the long-term sequelae of therapy and thus improve their quality of life.”

Reflecting on her clinical and research endeavors, Dr. Roth finds most rewarding her ability to help her patients through the entire arc of diagnosis through survivorship. “There are no words to express how rewarding it is to take someone from the point of hearing the most traumatic news of their life, support them through this personal crisis, and then watch them go on to graduate college, get married or have children,” she says. “It is just so amazing to help people through what is such a devastating and unexpected diagnosis for a young person.”