Education Program



Disclosure:

Melani: No relevant conflicts of interest to declare.

Diffuse large B-cell lymphoma (DLBCL), NOS is
a biologically and clinically heterogeneous entity. Most patients are treated at
diagnosis with curative intent, with 60% achieving durable remission following R-CHOP
chemoimmunotherapy. Patients with primary refractory or relapsed disease can be
cured with secondary therapies, although outcomes are poorer. Recent advances
in biologic insight, along with the development of numerous novel therapies, have led to a rapidly changing management algorithm. This session will discuss
expanding options in the frontline setting, the role of immunotherapy
approaches, including chimeric antigen receptor (CAR) T-cell therapy and
bispecific antibodies, as well as additional targeted agents that are leading
to improved outcomes.


Dr. Laurie Sehn will review approaches to
the frontline therapy of DLBCL. While R-CHOP has been the universal standard of
care for decades, recent phase 3 trials assessing novel combinations have
demonstrated improvement in outcomes, resulting in new therapeutic options. Dr.
Sehn will review data from these trials and discuss how they have influenced
current treatment strategies. This session will review some of the key biological
and clinical determinants that should be considered to optimize initial therapy,
including molecular subtype, stage of disease, clinical risk as measured by the
International Prognostic Index (IPI) score, and patient-related factors such as
age, comorbidities, and cardiac fitness. This talk will also review
ongoing clinical trials to anticipate how the future landscape may evolve.  


Dr. Gilles Salles will review immunotherapy
options that have emerged as highly effective therapies for DLBCL. CAR T-cell
therapy has shown curative potential and is routinely used in the third-line
setting or as second-line therapy for patients with refractory or early-relapsing
disease.  Similarly, CD3XCD20 bispecific
antibodies have demonstrated durable responses as monotherapy in the third-line
setting, and more recently in combination strategies at first relapse. Dr.
Salles will review the efficacy data supporting their use, as well as toxicity profiles.
He will consider appropriate patient selection and sequencing strategies to
maximize their benefit. He will also review novel agents under investigation
that may lead to future options.


Dr. Christopher Melani will review the
growing list of novel targeted agents and combinations demonstrating efficacy
in DLBCL. He will consider where approved treatments such as polatuzumab
vedotin in combination with bendamustine-rituximab, loncastuximab tesirine, tafasitamab-lenalidomide,
and brentuximab vedotin with lenalidomide-rituximab fit into current management
algorithms. He will also discuss promising agents under investigation,
including novel therapies targeting B-cell receptor signaling, apoptosis, and
lineage-restricted transcription factors. This talk will also review
combination strategies being explored to overcome treatment resistance.