ASH 2017 – Day Two
7:30 AM-9:00 AM
Myeloma: Biology and Pathophysiology, excluding Therapy: Genomics
Three more abstracts from this morning’s sessions used the MMRF’s CoMMpass data! Gene expression patterns are identified (Abstract 325) and new genes identified (Abstract 326) that are implicated in multiple myeloma development.
We were also proud that our own Senior VP of Research, Dr. Daniel Auclair, presented the first analysis of the MMRF Molecular Profiling Protocol, which builds on the MMRF Data Bank and provides actionable information on how patients can best treat their specific type of myeloma (Abstract 395).
Investigators at the Icahn School of Medicine at Mount Sinai used their network model of newly diagnosed MM from the MMRF CoMMpass study—called MMNET—to identify patterns of gene expression in patients with MM at diagnosis and at relapse (ABSTRACT 325). Dr. Alessandro Lagana who presented the study showed:
- In most patients new MM clones emerge at relapse in which one or more clones were replaced by other clones (or subclones)
- Clones/subclones are defined by the types of genetic mutations they expressed or the copy number of genes being altered
- Changes in presence of various subclones over time indicates selective pressure introduced by therapy
Jonathan Keats, PhD of Translational Genomics Research Institute presented his group’s comprehensive analysis of myeloma genomics from newly diagnosed MM patients using data from the MMRF CoMMpass study (ABSTRACT 326). His analysis of the genomic data from 591 patients told us the following information:
- In at least 1% of the patient data tested, 60 distinct genes that are mutated were identified
- Of the mutated genes identified, many of them are considered to be oncogenes (genes that have the potential to cause the development of multiple myeloma)
- Many other genomic events were identified such as loss-of-function and gain-of-function genes and these genes were found to be involved in cellular functions like cell division and DNA repair
9:30 AM-11:00 AM
Myeloma: Biology and Pathophysiology, excluding Therapy: Genomics of The Pathogenesis and Progression of Multiple Myeloma
The MMRF’s Daniel Auclair, PhD presented the MMRC’s work on the usefulness of a precision medicine approach in MM particularly those patients who may be running out of options (ABSTRACT 395). The MMRF Molecular Profiling Protocol (MPP) was used to molecularly profile 500 relapsed patients with the goal of identifying actionable genetic alterations (that is, genetic mutations that can be a specific site of action for a drug or treatment). The MPP analysis revealed the following:
- 76% of patient samples were found to harbor at least 1 actionable alteration
- In 10% of cases, the treating physician acted on the information with an applicable targeted agent
These results have spurred the launch of MyDRUG, a master protocol aimed at developing new myeloma regimens based on individual patient’s genomics.
4:30 PM-6:00 PM
Myeloma: Therapy, excluding Transplantation: Immunotherapy in Myeloma and Amyloid
The last session of the day is upon us and here we look at four abstracts on the exciting topic of immunotherapy! Three abstracts will cover the hot area of chimeric antigen receptor (CAR)-T cell therapy (Abstracts 505, 506, and 524). The fourth study focuses on the use of Darzalex (daratumumab) in smoldering myeloma patients (Abstract 510).
The investigators from the University of Pennsylvania led by Dr. Adam Cohen (ABSTRACT 505) presented their updated data on CAR-T cells that are directed against the B-cell maturation antigen (BCMA)—a protein found on the surface of most myeloma cells. Dr. Cohen’s update includes the use of different doses of BCMA-CAR T cells in patients with refractory MM and who had very limited treatment options. Some of the treatment groups received chemotherapy prior to BCMA-CAR-T cell infusions in order to enhance the activity of CAR-T cells by depleting patient lymphocytes. Dr. Cohen showed that:
- Of the 24 patients who received the BCMA-CAR-T cell infusions, 11 patients achieved at least a partial response
- Side effects included cytokine release syndrome (CRS) and neurotoxicity; there was one death on the study
Lingzhi Yan from Suzhou, China presented a small pilot study of 8 relapsed/refractory patients who received a combination of two types of engineered CAR-T cells: ones that target CD19 and ones that target BCMA (ABSTRACT 506).
All patients experienced acute cytokine release syndrome, but none experienced neurologic complications nor where there any treatment-related deaths. Only 6 of the patients could be evaluated for a treatment response and 4 of these patients experienced a partial response or better.
In a separate session on CAR-T cells, Dr. Jennifer Brudno of the NIH presented her work on the use of their institution’s BCMA-CAR-T cell therapy in patients with relapsed/refractory MM (ABSTRACT 524). Dr. Brudno showed:
- Nine of 11 patients who received BCMA-CAR-T cell therapy achieved a response
- Eight of 10 patients in whom minimal residual disease (MRD) was measured had achieved MRD negativity
- Toxicities such as cytokine release syndrome was significant but limited in duration and controllable
The results of these CAR-T cell trials continue to be promising, as patients who had run out of available treatment options are consistently responding. However, the potential for CRS and neurotoxicity is very real and serious, so it will be important for these trials to continue as planned and for patients who participate in the trials to be closely monitored. The MMRF is committed to supporting the continued development of this exciting therapy; stay tuned for an announcement before year-end about our $15M Immunotherapy Initiative!
The use of Darzalex alone to delay the progression of intermediate or high-risk smoldering myeloma (SMM) to symptomatic MM was investigated in a phase 2 trial by Dr. Craig Hofmeister at The Ohio State University (ABSTRACT 510). Patients in Dr. Hofmeister and colleagues’ study were given 1 of 3 different doses of Darzalex: a long intense, an intermediate, and a short intense dosing schedule. The preliminary study results initially show that response rates tended to be higher in the group that received the long intense dosing schedule compared to the other schedules and that Darzalex was well-tolerated. We await further updates on this trial!