IMS Studies Utilize CoMMpass Genomic Data in Multiple Myeloma Research

The data created by the CoMMpass longitudinal genomic profiling study (NCT01454297) was employed in several significant clinical trials presented at the 19th International Myeloma Society (IMS) annual meeting, according to a press release from the Multiple Myeloma Research Foundation (MMRF).¹

The CoMMpass, or Clinical Outcomes in Multiple Myeloma Personal Assessment of Genetic Profiles trial, which collected data from an estimated 1150 patients worldwide, provided data that were cited in 19 abstracts at IMS, including 4 oral presentations. It was also announced that the Multiple Myeloma Research Consortium presented results from the MyDRUG clinical trial (NCT03732703) that investigated targeted therapies with precision medicine in patients with multiple myeloma.

“Despite great strides in treatment, multiple myeloma remains incurable and often fatal, which is why the use of CoMMpass data, presented in 19 abstracts at the 19th IMS Annual Meeting, further validates the value and utility of our comprehensive genomic and clinical CoMMpass data,” said Hearn Jay Cho, MD, PhD, chief medical officer of the MMRF, in a statement.

The CoMMpass study, which started collecting data in 2011, is the largest longitudinal genomic data set in patients with multiple myeloma and has provided valuable resources on the biology and genetics of the disease. Patients’ genomic profiles are monitored from diagnosis of multiple myeloma and onward through each treatment and relapse to investigate the relationship between patient genetics and response to treatment.

The studies presented at IMS using CoMMpass include an analysis of the phase 2 CARDAMON trial (NCT02315716) that determined that patients with wild-type MGAM, CCDC168, PDXDC1, ABCC1 and S1PR2 genes had better responses to treatment with carfilzomib (Kyprolis) plus cyclophosphamide and dexamethasone, though these genes were not associated with driver mutations for multiple myeloma.² CoMMpass patients with this gene signature who had received carfilzomib had a median progression-free survival (PFS) of 58.8 months, whereas those who did not have the gene signature had a median PFS of 33.2 months (P = .0067), affirming this association.

Another study identified an extramedullary disease-like transcriptional program induced by bone marrow stromal cells. The stromal interactions make multiple myeloma cells more resistant to the effects of cytotoxic therapy and immunotherapy.³ The CoMMpass MMRF IA16 cohort was 1 of 3 independent patient populations used to confirm the prognostic significance of this discovery in identifying patients with high-risk disease prone to drug resistance and poor long-term survival.

“We are thrilled that the CoMMpass study has been used by hundreds of researchers worldwide and continues to generate meaningful learnings that have played a vital role in accelerating the pace of research that can now be translated to clinical care,” said Michael Andreini, CEO of the MMRF, in a statement.¹

The phase 1/2 MyDRUG study platform, which is guided by CoMMpass’s genomic data, is an umbrella study designed to test targeted therapies used in other disease types, but not yet approved for patients with multiple myeloma, in high-risk patients who demonstrate genetic alterations.

The MyDRUG investigators presented results of a sub-protocol of patients with patients with early relapsed multiple myeloma with mutations in NRAS, KRAS, or BRAF.⁴ Investigators administered the MEK inhibitor cobimetinib (Cotellic) alone and then in combination with ixazomib (Ninlaro), pomalidomide (Pomalyst) and dexamethasone based on cobimetinib’s efficacy in patients with skin cancer with these mutations. With a median duration of therapy of 12 months, 6 out of 7 patients who were enrolled responded to therapy with 4 partial responses and 2 very good partial responses. The combination also appeared to be safe.

Other research presented at IMS demonstrated the value of the CoMMpass data set in validating results of studies and linking the genetics of patients to their treatment outcomes.

“CoMMpass continues to be one of the most important drivers of myeloma research,” said Cho.¹ “The MMRF is committed to working closely with researchers across the globe to drive breakthroughs using CoMMpass data, with the goal of bringing us closer to accelerating a cure for every [patient with] myeloma.”

_References:

_{1. MMRF CoMMpass and MyDRUG studies drive discoveries in research presented at 19th IMS Annual Meeting. Multiple Myeloma Research Foundation. August 24, 2022. Accessed August 29, 2022. https://bit.ly/3pU1H4j}

_{2. Walker I, Khandelwal G, D’Arcy V, et al. From CARDAMON to CoMMpass: a mutational signature that predicts carfilzomib-specific outcomes in myeloma. Presented at: 19th Annual International Myeloma Society Meeting; August 25-27, 2022; Los Angeles, CA. Abstract OAB-018.}

_{3. Binder M, Szalat R, Fulciniti M, et al. High-risk multiple myeloma due to extramedullary diseaselike gene expression induced by bone marrow stromal cells. Presented at: 19th Annual International Myeloma Society Meeting; August 25-27, 2022; Los Angeles, CA. Abstract OAB-021.}

_{4. Kumar S, Jayasinghe R, Bianchi G, et al. Clinical and translational results of the myeloma developing regimens using genomics (MyDRUG) sub-protocol C1 targeting RAS mutations. Presented at: 19th Annual International Myeloma Society Meeting; August 25-27, 2022; Los Angeles, CA. Abstract OAB-047.}