Clinical trials for lymphoma, leukemia and multiple myeloma could improve outcomes for patients
DUARTE, Calif. — Clinical trials that lay the groundwork for novel lymphoma, leukemia and multiple myeloma treatments will be among the highlights of the annual meeting of the American Society of Hematology (ASH) in San Diego Dec. 3 to 6. The trials, presented by City of Hope physicians and researchers, could ultimately lead to innovative therapeutic approaches that improve survival and quality of life for patients with those and other diseases.
The ASH meeting, which will host more than 20,000 investigators working on blood diseases, including cancers, encourages clinicians and scientists working both ends of the bench-to-bedside translational research spectrum to discuss the latest results in marathon talks and poster sessions, often sharing the latest available research.
“The ASH meeting brings together the best and brightest physicians and researchers in hematology to discuss the most promising research and treatment in the field,” said Stephen J. Forman, M.D., leader of City of Hope’s Hematologic Malignancies and Stem Cell Transplantation Institute and the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation. “Patients around the world ultimately benefit from leading-edge research presented at ASH.”
Among the research presented by City of Hope scientists will be results of four clinical trials that lay the groundwork for novel leukemia, lymphoma or multiple myeloma treatments. Those studies address:
Combination therapy results for patients with relapsed or refractory Hodgkin lymphoma. While many patients with Hodgkin lymphoma are cured with initial chemotherapy, challenges remain for treating patients who face relapsed or treatment-resistant disease.
Alex Herrera, M.D., assistant professor in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation and a hematologist/oncologist, led a phase 1/2 study of 42 participants that tested the safety and antitumor activity of brentuximab vedotin — an antibody-drug conjugate that induces an anti-tumor immune response — combined with nivolumab for use in people with relapsed or treatment-resistant Hodgkin lymphoma. Nivolumab is an immunotherapy that can restore anti-tumor immune responses by blocking the PD-1 immune checkpoint pathway, which tumors hijack to evade the immune system. Since both agents have shown success when used independently to treat the disease, researchers believed a combination approach could improve complete response rates prior to a stem cell transplant, as well as long-term outcomes.
Herrera and his team found that the drug combination is a well-tolerated therapy for patients with relapsed or treatment-resistant Hodgkin lymphoma who have failed standard frontline chemotherapy. (Patients initially could have had treatment-resistant disease, or relapsed after entering a remission.)
Study results also suggest that the anti-tumor activity of this combination therapy may be a promising option for this patient population.
Herrera will share additional results at his ASH oral presentation on Monday, Dec. 5, at 4:30 p.m.
Novel therapy for acute myeloid leukemia. For newly diagnosed acute myeloid leukemia (AML) patients under the age of 65, standard treatment is induction chemotherapy, or high doses of drugs at a continuous rate in order to kill as many cancer cells as fast as possible.
While the standard combination of infused cytarabine for seven days plus anthracycline for three days (what’s known as 7+3 chemotherapy) results in a high complete response rate, a significant number of patients either experience treatment resistance or evidence of minimal residual disease.
This is why a group of researchers is seeking ways to enhance and deepen remissions for AML patients.
A phase 1b study involving Anthony Stein, M.D., co-director of the Gehr Family Center for Leukemia Research at City of Hope, and other researchers from across the country evaluated the safety and anti-leukemic activity of a therapy that added Vadastuximab Talirine (33A) to 7+3 chemotherapy. 33A is an antibody and drug combination that targets CD33, an antigen expressed by approximately 90 percent of AML patients. The drug delivered by 33A, a pyrrolobenzodiazepine dimer, is a more powerful killer of cancer cells than systemic chemotherapeutic drugs and is released directly into CD33-expressing cells.
Results from the study, which will be discussed at an ASH press briefing on Saturday, Dec. 3, at noon, included 42 patients that have shown that 33A can be safely combined with 7+3 therapy when accompanying treatment on days 1 and 4. An alternate schedule of single-day dosing on the first day of treatment is under investigation.
Adverse effects of the combination therapy and induction mortality rates were also similar to those reported using 7+3 alone in this AML population. A high remission rate was seen after one cycle of the treatment with the majority of those patients showing no signs of minimal residual disease.
Clinical trial examines autologous stem cell transplants in multiple myeloma patients. Multiple myeloma patients who receive an autologous blood stem cell transplant must also take medication after the procedure to kill cancer cells.
The largest randomized trial examining autologous transplants in multiple myeloma patients tested various drug combinations that patients took after the procedure. The study aimed to answer the question: What is the best option after a transplant to increase the length of remission?
The phase 3 randomized study involving two City of Hope physicians – Amrita Krishnan, director of the Judy and Bernard Briskin Center for Multiple Myeloma Research and professor in the Department of Hematology & Hematopoietic Cell Transplantation, and George Somlo, professor in the Department of Medical Oncology & Therapeutics Research – involved 758 patients who first received a transplant and high dose melphalan, a chemotherapy drug.
One group took an intense, short course of a combination of drugs known as “RVD,” or lenalidomide (R), an immunomodulatory agent, bortezomib (V), a proteasome inhibitor, and dexamethasone (D), a steroid that can augment the effects of those two drugs, followed by lenalidomide maintenance, a course of therapy aimed at keeping a patient in remission. A second group took just lenalidomide as a maintenance, and a third group underwent a second transplant followed by lenalidomide maintenance.
Multiple myeloma in 57 percent of the patients had not progressed after a 38-month period among patients who took the RVD consolidation and melphalan; similar results were seen in 56 percent of patients taking melphalan and lenalidomide, and 52 percent of patients taking lenalidomide. Overall survival for the three groups was 86, 82 and 83 percent, respectively.
Researchers concluded that progression-free and overall survival rates were comparable in all three groups. Thus, adding intensive therapies after the initial transplant (and before lenalidomide maintenance) did not significantly impact the outcomes for patients.
Study results will be discussed during an ASH late breaking abstracts session on Tuesday, Dec. 6, at 7:30 a.m.
Long-term outcomes of ASCT in HIV-infected patients. A retrospective study of 50 HIV-positive patients who received autologous stem cell transplant for treatment of non-Hodgkin lymphoma at City of Hope was led by hematologist Liana Nikolaenko, M.D. The study, in which all of the transplantation and follow-up analysis was done at City of Hope, is the single largest institution study reporting on long-term outcomes for autologous stem cell transplant in HIV-positive patients with non-Hodgkin lymphoma.
The analysis examined the long-term outcomes of people who received the transplant between January 1998 and December 2011. Prior to transplantation, 46 percent of patients — most of whom had aggressive non-Hodgkin lymphoma — were in complete remission, and 54 percent were in partial remission.
At the time of analysis, 35 out of 50 patients (70 percent) were alive, confirming the efficacy of that transplant in this patient population. In addition, the City of Hope research team found that second primary malignancies and opportunistic infections, which can be associated with autologous stem cell transplant, particularly in patients with HIV, were not major factors in mortality for this cohort, and neither was HIV infection. Of the 15 patients (30 percent) that died, the cause of death was relapsed disease in eight patients (53 percent).
Study results will be presented during an ASH presentation on Monday, Dec. 5, at 6 p.m.
About City of Hope
City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as one of only 47 comprehensive cancer centers, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the world. City of Hope is located in Duarte, California, just northeast of Los Angeles, with community clinics throughout Southern California. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and numerous breakthrough cancer drugs based on technology developed at the institution. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.