By Binod Dhakal, MD, MS
More than a century ago, the brilliant physicist Max Planck investigated an obscure subject and sparked a revolution in physics. A profoundly conservative thinker, Planck had to disavow some orthodox theoretical ideas to assume that the total energy of all atoms at each frequency of vibration came in discrete lumps, or “quanta.” This theory would become what we now call quantum mechanics, which has revolutionized our understanding of the microcosm. An abrupt change in the state of an atom in quantum mechanics — a quantum leap — would later become the epitome of success and advancement in physics. Recently, the cancer field has witnessed a quantum leap with a new generation of treatments called “immunotherapy.” Since the early days of the 19th century, when scientists attempted to harness the immune system by injecting live and inactivated bacteria, our understanding of immunotherapy has improved considerably. We are now entering a new frontier in medical innovation with an ability to reprogram patients’ own cells to attack a deadly cancer.
For several cancers, including multiple myeloma, immunotherapy is rapidly making inroads. Myeloma occupies a mid-range position across the tumor types depicting somatic mutations (and resultant neoantigens) and forms the theoretical basis of immune-based approaches. With the graft-versus-myeloma effect observed after donor transplantation, the recent regulatory approvals of monoclonal antibodies, and promising results of experimental cellular therapies, one can safely assume that immunotherapy will take center stage among myeloma therapies in the future. Immunotherapy will represent a second quantum leap after the “novel agents” of the early 2000s. Consequently, this year’s ASH annual meeting will dedicate an education session to the potential and challenges of several immunotherapeutic approaches in myeloma. Chaired by Nina Shah, MD, of the University of California San Francisco, Immunotherapy in Myeloma will focus on various classes of immunotherapy, including a rationale for the mechanisms of action, as well as a summary of clinical and safety data. Shah will focus on the target selection for chimeric antigen receptor T cells (CAR-Ts) in myeloma beyond the B-cell maturation antigen. She will not only highlight the unprecedented results of early phase I and phase II clinical data of CAR-T, but also discuss the challenges in integrating CAR-Ts in myeloma therapy.
Experience with anti–PD-1 axis checkpoint inhibition in myeloma has been sobering. Adam Cohen, MD, of the University of Pennsylvania, will discuss the bumpy start of these proteins and the urgent need for novel checkpoint inhibitors in myeloma. Additionally, he will highlight impressive clinical data with other “off-the-shelf” immune approaches, in particular the antibody-drug conjugates and bispecific antibodies. He will compare the clinical efficacy and safety data of these exciting compounds over cellular therapies.
Finally, Ivan Borrelo, MD, of John Hopkins University will discuss other non–CAR-T cellular therapy approaches and their role in future myeloma treatment. Vaccine-based approaches using dendritic cell vaccine or myeloma-derived proteins have generated tremendous interest in the past few years. Beyond the CAR-T approach, recent studies have aimed to engineer natural killer cells using CAR technology to increase their reactivity and recognition specificity toward myeloma cells. Similarly, to increase the number of tumor-derived targets, cellular therapies based on engineered (transgenic) T-cell receptor technologies have been developed. Other options include marrow-infiltrating lymphocytes (MILs) that rep- resent a T cell source with significant differences compared to peripheral T cells and have greater endogenous tumor specificity. One of the challenges of these exciting therapies is the timing and the rational partner, and Borrelo will elaborate on this in his talk. If you have any FOMO because you missed this outstanding session, we’ve got you covered. The same stimulating discussion will repeat on Monday, at 4:30 p.m. (Hall E1, Level 2, Orange County Convention Center – map it).
Dr. Dhakal indicated no relevant conflicts of interest.