February 2016, Vol. 5, No. 1

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CAR T-Cell Therapy Highly Active in Various Hematologic Malignancies

James Kochenderfer, MD

ASH 2015, ASH Highlights

kochenderfer-james98pxCAR T cells demonstrated consistent activity in advanced hematologic malignancies evaluated in multiple small clinical trials reported at the meeting.

Disease remission persisting for as long as 36 months occurred in 8 of the first 20 patients treated at the National Cancer Institute. The 40% overall response rate included 4 of 5 patients with treatment-refractory acute lymphoblastic leukemia (ALL).

All of the patients received a single infusion of donor T cells modified by the addition of anti-CD19 CAR. No patients received chemotherapy.

The treatment led to severe tumor lysis syndrome in some patients, but the known adverse effect proved manageable with conventional interventions.

“We have treated patients with very advanced malignancies, including some patients who failed all standard therapies and continued to progress after allogeneic stem cell transplantation, a last-chance therapy for these types of patients,” said James Kochenderfer, MD, of the Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.

The remaining 15 patients consisted of 5 each with chronic lymphocytic leukemia, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). One or more patients in each disease group responded to the therapy, said Kochenderfer.

Some patients have had dramatic responses, including an individual with high-burden DLBCL with large tumors involving the cranium and an orbital cavity. All evidence of the disease disappeared within 5 days of the CAR T-cell infusion.

The University of Pennsylvania has one of the most active CAR T-cell clinical programs in the country, and investigators reported findings from ongoing trials in non-Hodgkin lymphoma (NHL) and ALL.

NHL represents an emerging use of CAR T cells, and Penn researchers reported objective responses in 15 of 28 patients treated to date with the investigational anti- CD19 CAR T cells known as CTL019. All but 1 of the responses have been complete remissions.

The overall response rate consisted of responses in 8 of 11 patients with follicular lymphoma, 7 of 15 patients with DLBCL, and 1 of 2 patients with mantle cell lymphoma. The 28 patients had proved refractory to conventional therapies, including some who had progressive disease after stem cell transplantation. The median progression-free survival in patients with follicular lymphoma and DLBCL had yet to be reached after a median follow-up exceeding 14 months.

“Our early results in this trial provide increasing evidence for the role of personalized cellular therapies in patients with NHL,” said Stephen J. Schuster, MD, an associate professor at Penn’s Abramson Cancer Center.

Updated results from one of the largest clinical experiences in pediatric ALL showed a 93% overall response rate with CTL019. Stephan A. Grupp, MD, PhD, Director of the Cancer Immunotherapy Frontier Program at Children’s Hospital of Philadelphia, PA, reported that 53 of 59 patients treated with CTL019 had achieved complete remissions, most of which proved to be durable.

The 59 patients had a 6-month relapse-free survival (RFS) of 76% and a 12-month RFS of 55%. The 1-year overall survival was 79%.

After a median follow-up of 12 months, 34 patients remain in complete remission, including 6 patients who have received additional therapy, including stem cell transplants. Among 20 patients whose disease relapsed, 13 tested negative for CD19, which meant their disease was no longer amenable to anti-CD19 CAR T-cell therapy.

“The response rate and durability we are seeing are unprecedented in pediatric ALL,” said Grupp. “The results offer hope that personalized cellular therapies will be a powerful key to long-term control of this difficult disease.”

The Last Word - February 12, 2016

Personalized Medicine at FDA: 2015 Progress Report

One year after the initial observation by the Personalized Medicine Coalition (PMC) of an increased rate of personalized medicine approvals at the FDA Center for Drug Evaluation and Research (CDER), the most recent data show that the trend has continued, with oncology leading the way for the field.A new analysis [ Read More ]

Colorectal Cancer - February 11, 2016

BRAF Mutation in Colorectal Cancer

Anita Turk, MD; Dustin Deming, MD
Division of Hematology and Oncology,Department of Medicine
University of Wisconsin-Madison School of Medicine and Public Health
and University of Wisconsin Carbone Cancer Center, Madison, WI

Advances in molecular pathology have allowed for the widespread use of sequencing technologies to improve our ability to better understand the biology of each individual patient’s cancer. This allows for the personalization of treatment strategies depending on the molecular profile of the cancer. In colorectal cancer (CRC), mutations in KRAS [ Read More ]