BiTEs to the Fight

Cynthia Chmielewski |

The treatment of myeloma is rapidly changing. When I first attended the American Society of Hematology’s (ASH) Annual Meeting in 2012 Immunotherapy was still in its infancy. Although immunotherapy options were being evaluated in clinical trials, they were not available to myeloma patients in clinical practice. November, 2015 was dubbed the November to remember in myeloma history. Three new myeloma treatment options were FDA approved and brought to market-Daratumumab (Darzalex), Elotuzumab (Empliciti) and Ixazomib (Ninlaro). Both Darzalex and Empliciti are in a class of drugs known as monoclonal antibodies (MaBs) -a type of immunotherapy. The age of myeloma immunotherapy was born.

#ASH15 brought the excitement of another type of immunotherapy to myeloma. I remember the last day of that ASH meeting like it was yesterday. I sat anxiously in a late breaking abstract session listening to Dr. Kochenderfer present the results of the National Cancer Institute’s (NCI) BCMA CAR T-cell trial to a standing room only audience. Only 12 patients were treated on this NCI Phase 1 Trial and the results were not mature, but I knew deep down CAR T-cell therapy would make it to myeloma patients. (This year there were close to 20 CAR T-cell presentations in myeloma.) After Dr. Kochenderfer’s presenation I left that room very hopeful for the future of myeloma treatment. I already knew of the success of CAR- T cell treatment in ALL. Emily Whitehead, the first pediatric cancer patient to receive Car- T cell treatment, was my unsung hero.

Dr. Kochenderfer’s 2015 ASH Slide

Slide from Dr. Kochenderfer’s 2015 ASH Presentation

I heard of another kind of immunotherapy at #ASH17. The DREAMM-1 Trial showed great success with its first in human antibody conjugate– GSK2857916. Many experts picked this up and coming immunotherapy treatment which targets BCMA as the best new therapy presented at #ASH17. This antibody conjugate was described as both impressive and practical. GSK2857916 showed a single agent overall response rate of 60% and was given Breakthrough Therapy Designation by the FDA.

At ASH this year BiTEs were brought to the fight. A BiTE is a Bi-specific T-cell Engager. BiTEs are engineered proteins combining regions isolated from two different antibodies. They bind to both T cells and cancer cells. I was able to gain a better understanding of how BiTE technology works by visiting the AMGEN display at the convention center. I completed the interactive BiTE puzzle by creating a bridge to connect a T-cell to the BCMA antigen on surface of the myeloma cancer cell. I successful engineered a BCMA myeloma BiTE and put it to the fight. I was also fortunate to meet Jennifer, the Executive Medical Director at AMGEN, who is a member of the myeloma BiTE team. She helped me truly understand this mechanism of action. The BiTE data presented looked promising and may give CAR-T cells a run for their money! 70% of patients dosed with 400 ug/d had a response.

 

MaB’s, CAR T-cells, ADC’s and BiTEs are changing the face of myeloma treatment. I also heard a presentation on an anti-PD-L1 checkpoint inhibitor, Atezolizumab, being used in combination with Dara plus Lenalidomide or Pomalidomide at #ASH18 that showed promising results. Having all these new tools in our toolbox will greatly increase survival and hopefully lead to a cure. The future looks bright and I hope #ASH19 will bring more encouraging data.

by Cynthia Chmielewski AKA @MyelomaTeacher on Twitter

Search @MyelomaTeacher’s #ASH18 #MMSM Tweets to view slides of many of the Myeloma Trials being presented

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