ORLANDO, Fla., Dec. 7, 2015 /PRNewswire/ -- Two new international studies co-authored by Regional Cancer Care Associates (RCCA) researchers from the John Theurer Cancer Center (JTCC) at Hackensack University Medical Center and presented today at the American Society of Hematology (ASH) annual meeting shed new light on the potential clinical value of PD-1 immunotherapy blockade in the treatment of Hodgkin's lymphoma and multiple myeloma in patients whose cancers had relapsed or were unresponsive to standard therapies.
JTCC was among a select group of U.S.-based centers participating in both studies assessing the potential benefit of the Merck-developed PD-1 immunotherapy pembrolizumab (Keytruda®) along with lenalidomide (Revlimid®) developed by Celgene in these difficult-to-treat blood cancers.
"PD-1 blockade through checkpoint inhibitors to unleash the immune system has generated tremendous enthusiasm over the last few years in a number of cancers. This therapy, already approved in lung cancer, has also shown very promising results in highly refractory blood cancers," said Andre Goy, M.D., Chairman, JTCC and Chief, Division of Lymphoma, Hackensack University Medical Center. "These studies, and the nearly 40 papers being presented this week at ASH, demonstrate the dedication and participation of JTCC in the development of novel options for patients living with blood cancers. I am very proud to see how JTCC is involved in the unprecedented revolution happening in cancer care."
New PD-1 Therapy Shows Potential in Hodgkin Lymphoma Patients
The first study, titled, "PD-1 Blockade with Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Safety, Efficacy and Biomarker Assessment," was co-authored by Martin E. Gutierrez, M.D., director, drug discovery and Phase 1 Unit at JTCC, and provides updated results of a cohort of patients with classical Hodgkin lymphoma (cHL) from the KEYNOTE-013 study, a phase 1B multicenter multicohort trial of pembrolizumab in patients with blood cancers.
The study enrolled patients with relapsed or refractory cHL who were ineligible for or refused autologous stem cell transplantation, and who did not respond or relapsed after treatment with brentuximab vedotin.
Pembrolizumab was administered intravenously at a dose of 10mg/kg every two weeks for up to two years or until confirmed progression or unacceptable toxicity, with response assessed after 12 weeks and every eight weeks thereafter. Primary endpoints were safety and the rate of complete remission, and secondary endpoints were progression-free survival (PFS), overall survival (OS), overall response rate (ORR), duration of response (DOR) and biomarker assessment.
Of 31 evaluable patients, 65 percent responded, with five achieving a complete response (16 percent), 15 (48 percent) achieving partial response and seven (23 percent) demonstrating stabilization of disease. The most common treatment-related adverse events were hypothyroidism (16 percent), diarrhea (13 percent), nausea (13 percent) and pneumonitis (10 percent). The investigators concluded that pembrolizumab was "associated with a favorable safety profile and a high response rate in a very heavily pre-treated cohort of patients with cHL," and that "responses appear durable with ongoing follow-up."
Study of Combo Immunotherapies Show Promise in Multiple Myeloma Patients
The second study, "Pembrolizumab in Combination with Lenalidomide and Low-Dose Dexamethasone for Relapsed/Refractory Multiple Myeloma (RRMM)," was co-authored by David S. Siegel, M.D., Ph.D., chief, division of multiple myeloma at JTCC. The study is known as KEYNOTE-023, an ongoing open-label, phase 1, multicenter, nonrandomized dose-escalation trial evaluating the safety, tolerability and efficacy of the combination of pembrolizumab and lenalidomid with dexamethasone in patients with RRMM.
Patients with RRMM whose disease had failed to respond to at least two prior therapies were enrolled in the study. During the dose determination phase, patients were enrolled at 2 mg/kg of pembrolizumab every two weeks in combination with 10 mg or 25 mg of lenalidomide on days 1-21, with a weekly 40 mg dose of dexamethasone. After a preliminary therapeutic dose was established, additional patients were to be enrolled at a fixed dose of 200 mg of pembrolizumab, in combination with lenalidomide and dexamethasone in the dose confirmation and expansion arms of the study.
In the dose determination and confirmation phase, for which results for 17 patients are currently available, four patients received pembrolizumab 2 mg/kg and lenalidomide 10 mg, and 13 patients were treated with either 2 mg/kg or a fixed-dose of 200 mg pembrolizumab and 25 mg of lenalidomide. All patients received dexamethasone. Primary endpoints in the study were safety and anti-tumor activity.
With a median follow-up of 287 days, 13 of 17 patients responded to treatment, with four patients achieving a very good partial response and nine achieving a partial response. The most common treatment-related adverse events were thrombocytopenia (47 percent), neutropenia (41 percent), fatigue (29 percent) and anemia, hyperglycemia and muscle spasms (23 percent each). No dose-limiting toxicities were observed in the cohort of patients receiving 10 mg lenalidomide. Three patients in the 25 mg lenalidomide cohort experienced dose-limiting toxicities (grade 3-4 neutropenia, grade 3 infectious pneumonia, grade 3 tumor lysis syndrome), but all recovered without the need for treatment discontinuation. Based on these data, the optimal therapeutic dose was defined as pembrolizumab 200 mg in combination with lenalidomide 25 mg and dexamethasone 40 mg. The investigators concluded that preliminary KEYNOTE-023 results indicate the PD-1 blockade with this drug combination "is associated with a tolerable safety profile and promising antimyeloma activity in heavily pretreated patients with RRMM."
"The physicians who joined JTCC all came from the best cancer training programs in the world and are dedicated to advancing research and innovation to offer novel options for cancer patients," said Andrew L. Pecora, MD, FACP, CPE, Vice President of Cancer Services and Chief Innovation Officer at JTCC, who is recognized as an international expert in blood and marrow stem cell transplantation. "These two studies are part of the 39 JTCC presentations at ASH this year, demonstrating the contribution of our cancer program to the field."
About John Theurer Cancer Center at Hackensack University Medical Center
John Theurer Cancer Center is New Jersey's largest and most comprehensive cancer center dedicated to the diagnosis, treatment, management, research, screenings, preventive care, as well as survivorship of patients with all types of cancer.
Each year, more people in the New Jersey/New York metropolitan area turn to John Theurer Cancer Center for cancer care than to any other facility in New Jersey. The 14 specialized divisions feature a team of medical, research, nursing and support staff with specialized expertise that translates into more advanced, focused care for all patients. John Theurer Cancer Center provides comprehensive multidisciplinary care, state of the art technology, and access to clinical trials, compassionate care and medical expertise— all under one roof. Physicians at John Theurer Cancer Center are members of Regional Cancer Care Associates, one of the nation's largest professional hematology/oncology groups. For more information please visit www.jtcancercenter.org.
Keytruda® is a registered trademark of Merck & Co. Inc.
Revlimid® is a registered trademark of Celgene Corp.
SOURCE John Theurer Cancer Center