Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting

Abstract

Antibodies and chimeric antigen receptor-engineered T cells (CAR-T) are increasingly used for cancer immunotherapy. Small molecule inhibitors targeting cellular oncoproteins and enzymes such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, BCL-2, IDH1, IDH2, are biomarker-driven chemotherapy-free agents approved for several major hematological malignancies. LOXO-305, asciminib, “off-the-shelf” universal CAR-T cells and BCMA-directed immunotherapeutics as well as data from clinical trials on many novel agents and regimens were updated at the 2020 American Society of Hematology (ASH) Annual Meeting. Major developments and updates for the therapy of hematological malignancies were delineated at the recent Winter Symposium and New York Oncology Forum from the Chinese American Hematologist and Oncologist Network (CAHON.org). This study summarized the latest updates on novel agents and regimens for hematological malignancies from the 2020 ASH annual meeting.

Health economic evidence for the use of molecular biomarker tests in hematological malignancies: A systematic review

“…Likewise, a multigene targeted genomic analysis was evaluated as cost‐effective for AML, but not all genes in the panel are currently recommended in the ESMO clinical guidelines. Nevertheless, it is likely that companion diagnostics will become more prominent for patient clinical management with the expenditure of treatment contingent on the likelihood of patient response, especially as more novel, costly targeted therapies enter the market 3 . However, as most studies are from European countries and from the healthcare system perspective, results may not be directly applicable to other settings.…”

“…1 The 5-year survival from diagnosis in the United States (US) is 64% for leukemias, 87% for Hodgkin lymphomas, 73% for non-Hodgkin lymphomas, and 54% for myelomas, and challenges remain in managing relapsed disease and the long-term effects of cancer treatments on patients. [2][3][4] The economic cost of hematological malignancies is substantial, estimated at €12 billion in Europe 2012 arising from direct healthcare consumption, productivity losses, and informal care. 5 This all emphasizes the importance of providing better treatments and controlling overall costs.…”

Novel insights into the biomarkers and therapies for primary central nervous system lymphoma

“…Four CD19 targeted CAR T-cell therapies for r/r B-cell lymphoma have achieved FDA approval. 85 However, considering the risk of neurotoxicity from CAR T-cell therapy, initial trials on patients with PCNSL have not met the current medical needs. 86 Abramson and colleagues studied a refractory DLBCL patient with CNS involvement who was treated with CD19 CAR T-cells.…”

“…The most recently approved anti-CD19 CAR T-cell therapy lisocabtagene maraleucel (liso-cel) is for patients with r/r large B-cell lymphoma. 85 One goal of the recruiting phase II TRANSCENDWORLD trial (NCT03484702) is to evaluate the efficacy of liso-cel in PCNSL and SCNSL. The CAROUSEL trial (NCT04443829) is a phase I trial of autologous anti-CD19 CAR T-cell therapy following preconditioning lymphodepleting (LD) chemotherapy with cyclophosphamide, FDB, and pembrolizumab in r/r PCNSL, which will recruit soon.…”

Antibody-drug conjugates for the treatment of lymphoma: clinical advances and latest progress

“…It also induced a long-term response and considerably extended survival after treatment discontinuation. A phase I clinical trial (NCT03833180) of VLS-101 investigated patients who failed a median of 4 prior systemic therapies with MCL ( n = 15), CLL ( n = 7), DLBCL ( n = 5), FL ( n = 3), or MZL ( n = 1) [ 131 , 132 ]. The reported ORR was 47%, with 20% of MCL patients achieving a CR.…”