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Evidence-Based Oncology August 2018
CareMore's Togetherness Program Addresses a Symptom of Living With Chronic Illness: Loneliness
Robin Caruso, MSW, LCSW
A Family's Search for Better Treatment, Survival From Pediatric Brain Tumors
Mary Caffrey
Survivorship Care in AYA Patients: Battling the Loss to Follow-up
Samantha DiGrande
Healthcare Costs and Access for Young Adult Cancer Survivors: A Snapshot Post ACA
Michelle S. Landwehr, MPH; Samantha E. Watson, MBA; and Maia Dolphin-Krute, BFA
Survivorship Care Throughout the Cancer Journey
Don Champlain, MHA, RN, and Lucio Gordan, MD
From the Editor-in-Chief: What Happens Next?
Joseph Alvarnas, MD
Conference Coverage: NCCN Policy Summit 2018
Coverage by Mary Caffrey
Managed Care Updates
Reporting by Laura Joszt, Alison Rodriguez, and Jaime Rosenberg
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Clinical Updates
Reporting by Surabhi Dangi-Garimella, PhD; Laura Joszt; Kelly Davio; and Samantha DiGrande

Clinical Updates

Reporting by Surabhi Dangi-Garimella, PhD; Laura Joszt; Kelly Davio; and Samantha DiGrande

BrainChild-01 Will Evaluate CAR T Cells in Pediatric CNS Tumors

Investigators at Seattle Children’s Hospital have initiated enrollment in the BrainChild-01 trial, which is designed to test chimeric antigen receptor (CAR) T-cell therapy in children and young adults with relapsed/refractory brain and central nervous system (CNS) tumors. Intriguingly, the modified CAR T cells will not be infused intravenously—rather, they will be injected either directly at the site of tumor resection or into the ventricular system of the CNS.1 

According to the National Brain Tumor Society, about 28,000 US children are living with a brain tumor, and 46102 cases of childhood and adolescent primary malignant and nonmalignant brain and CNS tumors are expected to be diagnosed in 2018. Brain tumors surpass leukemia as the leading cause of cancer-related deaths among children and adolescents.

Direct infusion of CAR T cells into the resected tumor cavity in the brain is also being evaluated in adult patients. Speaking at the recent annual meeting3 of the American Society of Clinical Oncology, Amy B. Heimberger, MD, a professor in the Department of Neurosurgery at The University of Texas MD Anderson Cancer Center, told the audience that the process helps overcome the lack of T-cell infiltration in the tumor. Multiple intracranial infusions of interleukin-13 receptor α2 CAR T cells in the resected tumor cavity of a patient with recurrent multifocal glioblastoma, as well as in the ventricular system, resulted in a regression of intracranial and spinal tumors in that patient. The response was sustained for 7.5 months.

The phase 1 BrainChild-01 study expects to recruit 26 patients with recurrent or refractory HER2-positive CNS tumors. The participants will be treated with autologous CD4 and CD8 T cells transduced to express a HER2-specific CAR and a truncated human epidermal growth factor receptor polypeptide, or EGFRt. Children with HER2-positive tumors that have relapsed or are refractory to prior treatment and who meet the trial’s inclusion criteria4 will undergo apheresis.5 The collected T cells will then be genetically modified to target HER2 gene-expressing tumor cells, and the modified cells will be administered through an indwelling catheter in 2 phases:
  • A weekly dose for 3 weeks, followed by a week off and an examination period
  • Weekly dose for 3 weeks
Following evaluation of treatment impact, including magnetic resonance imaging, patients can receive 6 more courses of infusion if there are T cells available and patients have not had adverse effects.

Primary outcomes that the study plans to measure include safety and feasibility of administering the CAR T-cell infusion directly into the tumor cavity.

Secondary objectives include examining the distribution of CAR T cells in the cerebrospinal fluid, their diffusion into the bloodstream, and, if possible, monitoring HER2 gene expression in the tumors at diagnosis versus at recurrence.

BrainChild-01, as the trial is named, will initially leave out patients diagnosed with diffuse intrinsic pontine gliomas, or DIPG tumors, highly aggressive tumors found at the base of the brain. However, Seattle Children’s Hospital plans to include children needing treatment for DIPG tumors in future BrainChild trials.

  1. T-Cell immunotherapy for brain and central nervous system tumors. Seattle Children’s Hospital website. Published June 2018. Accessed July 5, 2018.
  2. Quick brain tumor facts. National Brain Tumor Society website. Accessed July 5, 2018.
  3. Dangi-Garimella S. Identifying rational immunotherapy combinations for glioblastoma: a progress report. The American Journal of Managed Care® website. Published June 2, 2018. Accessed July 5, 2018.
  4. HER2-Specific CAR T Cell Locoregional Immunotherapy for HER2-Positive Recurrent/Refractory Pediatric CNS Tumors. Updated June 20, 2018. Accessed July 5, 2018.
  5. Dangi-Garimella S. Q&A with Dr Jae Park on the promise of CAR-T cells in cancer care. The American Journal of Managed Care® website. Published February 16, 2017. Accessed July 5, 2018.

Research Highlights Long-Term Survival and Health-Related QoL in Patients With Newly Diagnosed MM

Research presented at the 2018 American Society of Clinical Oncology Annual Meeting identified predictors of long-term survival and health-related quality of life in patients with newly diagnosed multiple myeloma (MM).

The first abstract used data from the registry, a multicenter prospective observational cohort study in the United States designed to examine diagnostic and treatment patterns, clinical outcomes, and quality of life in patients with newly diagnosed MM, in order to identify characteristics associated with overall survival of 6 years or greater versus death at less than 6 years.1

As of February 2017, the median follow-up was 65.4 months. Baseline characteristics associated with overall survival of 6 years or greater included age (being 70 years old or younger); Eastern Cooperative Oncology Group Performance Status of grade 0 or 1 (being fully active or being restricted in physically strenuous activity but ambulatory); lower International Staging System stage, which is used to prognosticate MM severity; and lack of history of diabetes.

In addition, the investigators found that patients who had an overall survival of 6 years or longer also had higher rates of triplet treatment, stem cell transplant, and maintenance therapy (with or without stem cell transplant), as well as higher response rates.

The second abstract focused on patients with newly diagnosed MM who are ineligible for stem cell transplantation (SCT) as part of ALCYONE, an ongoing multicenter, open-label, phase 3 trial.2 Participants are not eligible for high-dose chemotherapy with SCT because of their age (65 years or older) or coexisting conditions. The trial has shown3 significant progression-free survival (PFS) with patients treated with daratumumab, bortezomib, melphalan, and prednisone (D-VMP) compared with patients receiving bortezomib, melphalan, and prednisone alone (VMP).

“Measuring patient-reported outcomes (PROs) alongside disease progression provides the patient perspective on quality of survival and the value of health-related quality of life (HRQoL) for treatment decisions,” the authors of the abstract explained.

Patients completed the European Organization for Research and Treatment of Cancer Questionnaire (EORTC QLQ-C30) and the EuroQol Questionnaire at baseline and every 3 months during treatment. A total of 350 patients were receiving D-VMP, and 356 received VMP. The investigators found better HRQoL in patients in the D-VMP arm, plus 59.7% of patients receiving D-VMP reported meaningful improvement in global health status, as measured by EORTC QLQ-C30, compared with 52% of patients receiving VMP.

“Improvements in HRQoL were consistent with the clinical benefit showing superior PFS of D-VMP over VMP alone,” the authors concluded.


1. Gasparetto C, Rifkin RM, Terebelo HW, et al. Predictors of long-term survival in newly diagnosed multiple myeloma (NDMM) patients (pts) enrolled in the Connect MM Registry. Presented at: 2018 American Society of Clinical Oncology Annual Meeting; June 1-5, 2018; Chicago, IL. Abstract 8037.

2. Gries K, Fastenau J, Chen Y, et al. Health-related quality of life in patients with newly diagnosed multiple myeloma who are ineligible for stem cell transplantation: results from the ALCYONE trial. Presented at: 2018 American Society of Clinical Oncology Annual Meeting; June 1-5, 2018; Chicago, IL. Abstract 8042.

3. Joszt L. Daratumumab approved as frontline treatment in newly diagnosed multiple myeloma. The American Journal of Managed Care® website. Published May 8, 2018. Accessed July 6, 2018.


Glasdegib Receives Priority Review Based on Results That Show Nearly Doubled OS in AML

Impressive phase 2 study results prompted the FDA to grant priority review designation to Glasdegib, an investigational oral smoothened inhibitor for treating adult patients with previously untreated acute myeloid leukemia (AML) in combination with low-dose chemotherapy (cytarabine).

Findings from the randomized phase 2 trial showed a 49.9% reduction in the risk of death for patients treated with glasdegib plus cytarabine compared with patients treated with cytarabine alone. The Prescription Drug User Fee Act goal date for the FDA’s decision is in December 2018.

“Patients with acute myeloid leukemia who are ineligible for intensive chemotherapy are in critical need of new treatment options to improve their overall survival,” Mace Rothenberg, MD, chief development officer of oncology at Pfizer Global Product Development, said in a statement.1

In the phase 2 BRIGHT 1003 study, a randomized, open-label, multicenter trial, 88 patients received 100 mg daily of glasdegib with 20 mg of cytarabine twice daily, and 44 patients received cytarabine alone. The median overall survival (OS) was 8.8 months for patients treated with glasdegib, whereas the patients on cytarabine alone had a median OS of 4.9 months.

The phase 2 trial results were originally presented at the 58th American Society of Hematology Annual Meeting and Exposition. After the findings were reported, Jorge Cortes, MD, an investigator in the trial and deputy chair and professor of medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, explained that glasdegib works by disrupting the Hedgehog pathway, which is thought to play a role in the development of multiple types of cancer.

“The Hedgehog pathway is a compelling target in cancer research because of the ability to target and disrupt the root of the cancer; that is, the cancer-originating cell,” Cortes said in a statement in December 2016.2 “As the first smoothened inhibitor to demonstrate clinical benefit in patients with AML and high-risk MDS [myelodysplastic syndrome] who were ineligible for intensive chemotherapy, these results with glasdegib provide hope that interfering with this pathway may lead to potential new treatment options for blood cancers that may improve patient outcomes.”

The most common serious adverse effects were febrile neutropenia (29% of patients in the glasdegib arm vs 20% in the cytarabine alone arm) and pneumonia (21% vs 17%).

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