Lymphoma and Myeloma Program Project Summary / Abstract The Lymphoma and Myeloma Program characterizes specific lymphoid and plasma cell malignancies at the cellular and molecular level using state-of-the-art approaches, including informative murine models, patient tumors, and comprehensive analyses of molecular signatures. Program members then translate the emerging insights into innovative clinical trials. Members include: 1) investigators with lymphoma and myeloma research programs that span basic, translational and clinical research; 2) dedicated clinicians; 3) hematopathologists; and 4) computational biologists and biostatisticians with a focus on these diseases. Their historic and recent efforts have identified new rational treatment targets and moved promising targeted inhibitors from laboratories into the clinic. Program members also have longstanding interest and contributions in the analysis and augmentation of host immune responses to lymphoma and myeloma. Engagement with the Cancer Center’s catchment area (Massachusetts) and training of the next generation of Lymphoma and Myeloma researchers are integral Program elements. The Program’s 74 members (47 primary and 27 secondary) represent five DF/HCC institutions and 9 academic departments. In 2019, peer-reviewed grant funding attributed to the Program was $5.4 million in direct costs from the NCI and $5.6 million from other sponsors. During the current funding period, primary Program members published 933 cancer-relevant papers. Of these, 27% were inter-institutional, 23% were intra- programmatic, and 36% were inter-programmatic collaborations between two or more DF/HCC members. For the next CCSG finding period, our Specific Aims are to: 1) Elucidate pathogenic mechanisms underlying specific lymphoid/plasma cell neoplasms; 2) Develop novel therapeutic approaches to lymphoid and plasma cell neoplasms; and 3) Evaluate early intervention and prevention in patients with precursor conditions for hematologic malignancies. To realize these Aims, Program members will avail of invaluable CCSG resources: core facilities, collaborative structures, the CCEE and OCRET functions, and a clinical trials infrastructure that is highly effective for bench-to-bedside translation.