TY - JOUR
T1 - Navigating between Scylla and Charybdis
T2 - A roadmap to do better than Pola-RCHP in DLBCL
AU - Munoz, Javier
AU - Deshpande, Anagha
AU - Rimsza, Lisa
AU - Nowakowski, Grzegorz S.
AU - Kurzrock, Razelle
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/3
Y1 - 2024/3
N2 - In treating diffuse large B-cell lymphoma (DLBCL), oncologists have traditionally relied on the chemotherapy backbone of R-CHOP as standard of care. The two dangers that the hematologist must navigate between are the aggressive disease (Charybdis that in the absence of therapy systematically destroys all the ships) and the toxicity of the therapies (Scylla with its six monstrous heads that devours six crew members at a time), and hematologists have to navigate very carefully between both. Therefore, three different strategies were employed with the goal of improving cure rates: de-escalating regimens, escalating regimens, and replacement strategies. With a replacement strategy, a breakthrough in treatment was identified with polatuzumab vedotin (anti-CD79B antibody/drug conjugate) plus R-CHP. However, this regimen still did not achieve the elusive universal cure rate. Fortunately, advances in genomic and molecular technologies have allowed for an improved understanding of the heterogenous molecular nature of the disease to help develop and guide more targeted, precise, and individualized therapies. Additionally, new pharmaceutical technologies have led to the development of novel cellular therapies, such as chimeric antigen receptor (CAR) T-cell therapy, that could be more effective, while maintaining an acceptable safety profile. Thus, we aim to highlight the challenges of DLBCL therapy as well as the need to address therapeutic regimens eventually no longer tethered to a chemotherapy backbone. In the intersection of artificial intelligence and multi-omics (genomics, epigenomics, transcriptomics, proteomics, metabolomics), we propose the need to analyze multidimensional biologic data to launch a decisive attack against DLBCL in a targeted and individualized fashion.
AB - In treating diffuse large B-cell lymphoma (DLBCL), oncologists have traditionally relied on the chemotherapy backbone of R-CHOP as standard of care. The two dangers that the hematologist must navigate between are the aggressive disease (Charybdis that in the absence of therapy systematically destroys all the ships) and the toxicity of the therapies (Scylla with its six monstrous heads that devours six crew members at a time), and hematologists have to navigate very carefully between both. Therefore, three different strategies were employed with the goal of improving cure rates: de-escalating regimens, escalating regimens, and replacement strategies. With a replacement strategy, a breakthrough in treatment was identified with polatuzumab vedotin (anti-CD79B antibody/drug conjugate) plus R-CHP. However, this regimen still did not achieve the elusive universal cure rate. Fortunately, advances in genomic and molecular technologies have allowed for an improved understanding of the heterogenous molecular nature of the disease to help develop and guide more targeted, precise, and individualized therapies. Additionally, new pharmaceutical technologies have led to the development of novel cellular therapies, such as chimeric antigen receptor (CAR) T-cell therapy, that could be more effective, while maintaining an acceptable safety profile. Thus, we aim to highlight the challenges of DLBCL therapy as well as the need to address therapeutic regimens eventually no longer tethered to a chemotherapy backbone. In the intersection of artificial intelligence and multi-omics (genomics, epigenomics, transcriptomics, proteomics, metabolomics), we propose the need to analyze multidimensional biologic data to launch a decisive attack against DLBCL in a targeted and individualized fashion.
KW - DLBCL
KW - Polatuzumab vedotin
KW - Targeted therapy
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U2 - 10.1016/j.ctrv.2024.102691
DO - 10.1016/j.ctrv.2024.102691
M3 - Review article
C2 - 38310754
AN - SCOPUS:85184063017
SN - 0305-7372
VL - 124
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
M1 - 102691
ER -