ASH 2016: Innovative new trials show promise for lymphoma and multiple myeloma patients

December 7, 2016 | by City of Hope

City of Hope physicians recently announced the findings from several studies at the annual American Society of Hematology (ASH) conference held in San Diego from Dec. 3 to 6.

Numerous clinical trials, which lay the groundwork for novel approaches to lymphoma and multiple myeloma therapies, could ultimately lead to new treatments that improve survival and quality of life for patients with those and other diseases. Additional studies give new insight into best practices for the treatment of various blood cancers.

The ASH meeting hosted more than 20,000 investigators working on blood diseases and cancers. The conference is an opportunity for clinicians and scientists to discuss the latest available research in a series of marathon sessions.

“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 involving City of Hope scientists presented at ASH were the following studies:

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 study of 42 participants that tested the safety and anti-tumor activity of brentuximab vedotin — a drug that encourages an anti-tumor immune response — combined with nivolumab, which works by blocking something called the PD-1 immune checkpoint pathway, which tumors often hijack to evade the immune system.

The study was designed to explore the drug combination’s effectiveness in people with relapsed or treatment-resistant Hodgkin lymphoma, and Herrera and his team found that the therapy was well-tolerated. Study results also suggest that the anti-tumor activity of this combination therapy may be a promising option for this patient population.

“This exciting study demonstrates that immunotherapy can be safely used earlier in the course of treatment in patients with Hodgkin lymphoma,” Herrera said. “Our preliminary findings suggest that a chemotherapy-free, immunotherapy-based regimen can potentially be an effective and less toxic bridge to autologous stem cell transplantation.”

Novel therapy for acute myeloid leukemia

For newly diagnosed acute myeloid leukemia (AML) patients under the age of 65, standard treatment involves induction chemotherapy, high doses of drugs administered at a continuous rate in order to kill as many cancer cells as fast as possible.

While the standard combination of cytarabine and anthracycline often results in a high response rate, a significant number of patients either experience treatment resistance or evidence of residual disease. Thus, researchers have begun seeking ways to enhance and deepen remissions for AML patients.

A 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 the traditional cytarabine-anthracycline combination. 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 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 included 42 patients, demonstrated that 33A can be safely combined with traditional drug therapy. 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 – that is, a transplant that involves stem cells that come from a patient’s own blood – must also take medication after the procedure to kill cancer cells.

A large 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 study involved two City of Hope physicians: Amrita Krishnan, M.D., 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, M.D., professor in the Department of Medical Oncology & Therapeutics Research, who looked at 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. This was 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.

In 57 percent of patients who took the RVD consolidation and melphalan, multiple myeloma had not progressed after a 38-month period. 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.

“This was a highly awaited trial as it asked and answered a major question in the era of modern myeloma therapy: What is the best thing to do after initial autologous transplant?” Krishnan said. “It suggests that – at least in the United States – there does not seem to be a role for tandem transplant.”

Long-term outcomes of ASCT in HIV-infected patients

A retrospective study of 50 HIV-positive patients who received an 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 institutional look at 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 effectiveness 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).  

 “Our study, with median follow up of over five years, was able to answer important questions of long-term outcomes for patients with HIV- associated lymphoma, in general considered a poor prognosis,” Nikolaenko said. “We now know that these patients can do well with high-dose therapy followed by stem cell transplantation and should be offered such treatment in the setting of relapsed lymphoma, which are the same indications as for non-HIV patients.”

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