The ASH21 Meeting of blood diseases is in the books. What I can share with patients, care partners, and all who are interested is that the myeloma research world is on fire! There are so many new questions for new and veteran researchers, so many creative possible solutions were a part of this annual meeting with a usual attendance of 30,000 health professionals with interests in hematology.
I wanted to share the many advancements being made in the myeloma world – to be able to communicate hope for treatment options and high hopes for a cure for multiple myeloma (MM). There was something new at every level of myeloma treatment — from the newly diagnosed to those who are considered to have relapsed/refractory multiple myeloma (RRMM).
There were an incredible 879 myeloma-related abstracts submitted to the conference — a compelling evidence of increasing interest and progress in this rare cancer by researchers from all over the world. This was a huge increase compared to the number of myeloma abstracts during my first ASH conference 7 years ago in 2014.
The science was sometimes difficult for me to follow, but I knew I would have several opportunities, including leaning on team members to try to understand the mechanisms of new therapies. I knew that I should not get distracted by trying to follow p-values, levels of significance or by understanding the intricacies of targeted therapies. These targeted therapies are moving us closer to precision or personalized medicine. I could gain better understanding of the biology of multiple myeloma and the new strategies to control it.
Some outstanding advances included the seeming omnipresence of the monoclonal antibody, daratumumab, in many therapies – both front line and after three or four therapies. Daratumumab was approved by the FDA in 2015 along with three other drugs. It is interesting to see it taking center stage in combination with various other drugs. The evidence of several clinical trials shows that there may be a change from the current “gold standard” of newly diagnosed myeloma therapy —from three drugs to four drugs.
Population Studies and Biologic Determinants of Myeloma Control
There were several important progress reports on two population studies, one of which is the iStopMM Study (Iceland Screens, Treats, or Prevents Multiple Myeloma) —a part of the Black Swan Research Initiative (BSRI) of the IMF. In this innovative nationwide, randomized clinical trial (RCT), approximately 80,000 adults over 40 years of age who consented to participate were screened for the myeloma precursor monoclonal gammopathy of undetermined significance (MGUS). There were an impressive eight presentations from this clinical trial, including four oral and the remainder poster presentations. One of the significant results is the occurrence of MGUS, expected in the general population as they increase in age. Smoldering multiple myeloma (SMM) incidence was higher than expected. Observations have determined that the use of mass spectrometry versus Serum protein electrophoresis (SPEP) should be used to determine myeloma protein levels.
Because of this unique longitudinal trial, there is genetic sequencing information on all volunteer participants. Finding SMM during screening can allow earlier intervention. The question arises as to whether widespread screening is advisable. The ethics of screening without having an appropriate treatment plan needs to be considered. The results of the studies that come from this trial are highly significant, but come with the limitation of being a homogeneous, virtually all-white population.
Early results from another population clinical trial called the PROMISE Study were presented. In contrast to the demographics of the iStopMM study, the PROMISE Study enrolled myeloma patients 40 and over who self-identified as African American or Black and patients of any race who had a family history of myeloma.
Over 7,200 were screened using SPEP and mass spectroscopy. Overall, MGUS was detected in 10% of volunteers using mass spectroscopy, 6% using SPEP. Some subgroups showed even higher prevalence of MGUS, like African Americans over age 50 with 17% MGUS using mass spectrometry. Clearly, these population studies with different demographics —age, race/ethnicity, geography, genetic sequencing, etc.— will help us unravel the many mysteries of myeloma.
New Approaches to Myeloma Control
Other study results focused on immunotherapy called CAR T therapy, including ABECMA® (idecabtagene vicleucel). On March 26, 2021, the FDA approved idecabtagene vicleucel (also called ide-cel), which targets B cell maturation antigen (BCMA) protein that lives on the myeloma cell. There has been so much work since this therapy was first introduced to reduce major side effects and the expense of CAR T as major barriers for access to this therapy.
The reported outcomes demonstrate remissions that are deeper and last longer, allowing patients and their families a longer period of no treatment. With these advances, there was discussion among some scientists that someday CAR T therapy might replace stem cell transplant as a consideration for earlier therapy than after four prior treatments.
Another major area of research and hope for those who have already been heavily treated for myeloma is the research of bispecific antibodies – an emerging immunotherapy. Bispecific T-cell Engagers (BiTEs) are antibodies that simultaneously target BCMA or other proteins, GPRC5D, and FcRH5 and immune effector cells (like T-cells). Research on all these therapies is ongoing with reports especially on working to decrease side effects like cytokine release syndrome (CRS), cytopenia, and infections.
Social Determinants of Health
I was excited to witness more attention being given to the equally important Social Determinants of Health (SDoH). With all the bench research, and phases I-IV of clinical trials, translating that research to delivery of results to patients and communities must also take center stage. I was encouraged to see the Anti-Racism Studio as a part of the daily agenda at ASH. I believe this heightened awareness of the need for diversity in clinical trials and suggestion from the audience could move the inclusion of diversity in research to a policy level at these scientific sessions. We have to include community engagement in the recruitment of “partners or participants,” not “subjects” to clinical trials. We have to learn from studies like iStopMM and take the clinical trial to the community to remove barriers to participation, such as transportation. We need to consider institutional racism and unconscious bias on the part of providers to be successful in equitable access to care. We should find ways to ensure that all myeloma patients will have access to newly discovered therapies —removing yet another potential barrier to participation. Acknowledging and monitoring for health equity is essential.
I am honored and humbled to be a member of this patient advocate team. It still melts my heart each time I see and hear a researcher-presenter include patients and participants in their acknowledgments. I extend my sincerest appreciation to the IMF and all the sponsors who supported our attendance at this very important annual ASH meeting.
Gail McCray, on Twitter @IMFgailMYELOMA