C1As

Although molecularly targeted therapies have shown efficacy in other hematologic malignancies, currently venetoclax is the only targeted therapy approved for MM (t(11;14))...It addresses gene therapies, small molecule inhibitors and monoclonal antibodies currently under investigation to antagonize oncogenic drivers including MCL-1, BCL9, F11R, and CKS1B, all of which are implicated in cell survival, proliferation or drug resistance. In conclusion, the link between chromosome 1 abnormalities and high-risk disease in MM patients offers a compelling rationale to identify and explore therapeutic targeting of chromosome 1 gene products as a novel precision medicine approach for a poorly served patient population.

P1/2, N=20, Active, not recruiting, Ciusss de L'Est de l'Île de Montréal | Trial primary completion date: Sep 2021 --> Oct 2023

P2, N=40, Completed, Maisonneuve-Rosemont Hospital | Active, not recruiting --> Completed

The PFS and OS of patients with combined abnormalities of del (1p13.3)/1q21gain or amp was significantly worse compared to del(1p13.3) alone and 1q21gain or 1q21 amp alone, which identifies a subset of patients with poor clinical outcomes.

However, more effective therapeutic approaches are still needed to overcome the negative impact of C1As. Therefore, we summarize the prevalence, pathogenesis, clinical significance and present therapeutic condition of C1As in MM, and attempt to conclude the precise and personalized management for patients with C1As.

P1/2, N=20, Active, not recruiting, Ciusss de L'Est de l'Île de Montréal | Recruiting --> Active, not recruiting

P1/2, N=20, Recruiting, Ciusss de L'Est de l'Île de Montréal | Trial completion date: Mar 2024 --> Sep 2025 | Trial primary completion date: Mar 2022 --> Sep 2021

Concomitant del 1p with 1q21 gain and /or amp was present in 8% of patients. The PFS and OS of patients with combined del1p/1q21gain abnormalities was significantly worse compared to del 1p alone and 1q21 gain alone and thus identifies a subset of patients with poor clinical outcome.

Our data suggest that KRAS / NRAS / BRAF mutations may play an important role in the development of EMD. These and other associated molecular abnormalities portend a poorer prognosis and may provide novel therapeutic insights.

Our pilot study revealed an association of chromosome 1 abnormalities in bone marrow myeloma cells with extramedullary progression. Optical mapping showed the potential for refining the complex genomic architecture in MM and its phenotypes.