#ASH16- More Choices, Better Outcomes
Every December approximately 25,000 hematologists and researchers from around the world gather together for the annual meeting of the American Society of Hematology (ASH). The International Myeloma Foundation (IMF) has invited me to attend this meeting with them for the last 5 years. The IMF selects a group of educated patient advocates to attend ASH and cover this hematology conference using various avenues of social media from a patient’s perspective. The International Myeloma Foundation is able to bring patients to ASH due to generous educational grants from our pharmaceutical partners. The myeloma community is very fortunate that our pharma partners value the voice of their patient constituency.
This year’s ASH meeting was held in San Diego. The weather was beautiful and the venue was extremely large. I walked over 10,000 steps a day! After last’s year’s “November to Remember” (3 new myeloma drugs FDA approved within a 3 week time frame) I didn’t think this year’s ASH would prove as exciting. Boy was I wrong! There were over 700 oral and poster presentations focusing on myeloma. The rooms where the myeloma abstracts were being presented were overflowing and excitement was in the air. Many of the abstract presentations showed promising results.
Two themes I noticed during this year’s ASH was a focus on Immunotherapy and more emphasis being placed on how different treatments worked for subgroups of the myeloma population.
A Focus On Immunotherapy—Monoclonal Antibodies, Checkpoint Inhibitors and CAR-T Cell Therapy:
Immunotherapy is a way to use the body’s own immune system to identify and attack cancer. There are different ways the immune system can do this. Sub-types of immunotherapy include monoclonal antibodies, checkpoint inhibitors and CAR-T cell therapy.
Monoclonal antibodies used to treat cancer are made in a laboratory. A laboratory-made antibody is designed to function like a naturally occurring antibody and to target a specific single protein on the surface of cancer cells. Once the target is found on the cell’s surface the antibody then attacks. Daratumumab and Elotuzumab are two FDA approved monoclonal antibodies used in the treatment of myeloma. Isatuximab is a monoclonal antibody that is still under development for myeloma and is showing positive data. Data from the POLLUX and CASTOR trials show that Daratumumab is very efficacious with dexamethasone and either Revlimid or Velcade. This also held true for the hard to treat subgroup of myeloma patients that are considered high-risk by cytogenetic features (HRMM). The POLLUX trial showed that the overall response rate for HRMM was 89% vs 67% when comparing Daratumumab/Revlimid/Dex vs Revlimid/ Dex. I was glad to see that treatment outcomes for various trials were presented with response by cytogenetic risk status. This leads me to believe that there will be a push towards precision treatment in the future.
Checkpoint inhibitors are another category of monoclonal antibodies. Checkpoint inhibitors are monoclonal antibodies that target proteins found on the immune system’s T-cells. T-cells are a type of white blood cell that circulate around our bodies, scanning for cellular abnormalities and infections. Once these abnormalities are located T-cells attack and destroy the invader. Checkpoint inhibitors work by either blocking molecules that stop T-cells from working properly or by turning on molecules that stimulate T-cells to work better. Checkpoint inhibitors “take the brakes off the immune system” allowing the immune system to attack cancer cells. The checkpoint inhibitor pembrolizumab is being evaluated in several clinical trials in myeloma. Pembrolizumab used in combination with pomalidomide and dexamethasone shows promising durable therapeutic activity and an acceptable safety profile in highly pre-treated relapsed/refractory myeloma.
CAR–T cells are Chimeric Antigen Receptor- T-cells. In this therapy option T-cells are collected from a patient. Then T-cells are reengineered in a laboratory to produce chimeric antigen receptors (CARs) on their surface. The reengineered CAR-T cells are multiplied in the laboratory. Once expanded the CAR -T cells are then infused into the patient.
In myeloma this is usually done after an autologous stem cell transplant. CAR-T cells that have been returned to the patient’s bloodstream multiply in number. These are the “attacker” cells that will recognize, and kill, cancerous cells that have the targeted antigen on their surface. Some surface antigens that are being used in myeloma are CD19, CS1 and BCMA. These trials are showing success, but are in the very early phases of development.
Three new agents: Selinexor, Venetoclax and Nelfinavir:
Three new agents caught my eye this year at ASH- Selinexor, Venetoclax and Nelfinavir. Selinexor, an oral drug which inhibits CRM-1, is showing promise in quad and penta refractory myeloma patients. Venetoclax another oral drug that is currently approved to treat chronic lymphocytic leukemia is effective in refractory myeloma. Nelfinavir is an HIV drug which has been found to be very useful in reversing proteasome inhibitor refractory myeloma. I took a Twitter poll of my followers to see who they would vote for as “Rookie of the Year”. Almost 50% of the 41 respondents choose Venetoclax. This BCL-2 inhibitor is one of the first therapies that appears to have impact on a specific sub-type of multiple myeloma. Venetoclax kills myeloma cells, especially for patients with an 11;14 translocation. Patients with this translocation typically have high BCL-2 levels. Venetoclax may be myeloma’s first Precision Treatment option!
I hope to see more of this Precision Medicine approach in the future especially since the data from the Multiple Myeloma Research Foundation’s (MMRF) CoMMpass Study is maturing. There were a record-breaking 19 research presentations from the CoMMpass Study at ASH. According to these presentations the CoMMpass Study data is already yielding insights into new targets and pathways for drug development, as well as new ways to identify and potentially treat high-risk patients. Three research groups have identified sets of genes and pathways found in patients that relapse quickly. According to the MMRF some of these mutations could be treated with drugs currently used for other cancers while others are new targets for drug development. Initiatives are underway to find common traits among high risk patients so more precise treatment protocols can be developed.
Patient Advocates are playing a bigger role at medical conferences. Patients are connecting with healthcare professionals and researchers at these meetings. Patients and the medical community are building relationships. This benefits both the patient and the medical community. By attending conferences and listening to the presentations, patient advocates learn first-hand about the exciting research that is being done. In turn advocates share with their communities what advances have been made and why it is important to consider clinical trials when evaluating treatment options. The patient perspective and experience is invaluable to the research community when treatments are evaluated. I hope that the patient presence at medical meetings will continue to evolve and grow. I believe if we work as partners in research cures will be found faster.
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|Cynthia Chmielewski was diagnosed with multiple myeloma, a blood cancer, in 2008. Cindy’s induction therapy stopped working after a few cycles and she proceeded with a stem cell transplant which failed to put her into remission. Depressed and scared she continued her fight using newly FDA-approved targeted therapies which eventually put her in remission. Cynthia continues treatment with a maintenance protocol. Cynthia is using her passion for education to teach a new group of “students” – myeloma patients, their caregivers and others interested in myeloma. She is a trained mentor, advocate and Patient Ambassador.|