Saving changes...

Done

Error

VCS 2020: Enhancing the efficacy of immunotherapy in diffuse large B cell lymphoma (DLBCL) using rational combination approaches

VCS 2020: Enhancing the efficacy of immunotherapy in diffuse large B cell lymphoma (DLBCL) using rational combination approaches

VCS 2020: Enhancing the efficacy of immunotherapy in diffuse large B cell lymphoma (DLBCL) using rational combination approaches

Cheryl London
Cheryl London
on behalf of Missouri Veterinary Medical Association

$FREE $ FREE $ FREE

$ FREE $ FREE $ FREE
$ 25.00 $ 25.00 $ 25.00
Normal Price: FREE $25.00

Review:

Launch date: 22 Nov 2020
Expiry Date:

Last updated: 26 Jan 2021

Reference: 196331

Maximum Attendees:

Places Left: 0

This course is no longer available

Exam is embedded in the course
No preview available
No Exam Available

Latest User Comments

I would like to...

Course Availability

This course is only available to trainees days after purchase. It would need to be repurchased by the trainee if not completed in the allotted time period. This course is no longer available. You will need to repurchase if you wish to take the course again.

You have null days left.

Description

Topic: Enhancing the efficacy of immunotherapy in diffuse large B cell lymphoma (DLBCL) using rational combination approaches
Despite the addition of rituximab to CHOP chemotherapy in the treatment of diffuse large B cell lymphoma (DLBCL), up to 40% of human patients ultimately succumb to their disease. Additionally, those patients effectively cured have a high risk of long-term morbidities secondary to treatment. As such, novel approaches that reduce the intensity of chemotherapy while simultaneously improving outcomes through combination with small molecule inhibitors/immunotherapeutics are desirable. Unfortunately, exploration of such treatment strategies is typically relegated to patients with relapsed/refractory disease where efficacy is likely to be lower. It is now clear that DLBCL in dogs resembles the human disease with respect to clinical presentation, molecular aberrations, and genomic alterations making it a good spontaneous large animal model of disease. As such, we have been leveraging canine DLBCL to rapidly evaluate the activity of rational small molecule inhibitors targeting PI3Kδ (RV1001), NAMPT/PAK4 (KPT-9274), or SUMO-Activating Enzyme (TAK-981) combined with immunotherapy (anti-CD20, from Elanco), with the ultimate goal of identifying the most effective combination to move forward in human patients. Using an adaptive mini-pilot trial approach in the front-line setting we are assessing the activity and toxicities of anti-CD20/targeted small molecule combinations in affected dogs and correlating clinical, biological, and genomic biomarkers to develop signatures that predict response to therapy and long-term progression-free survival. Our data demonstrate that anti-CD20 effectively depletes B cell populations in treated dogs and that treatment with RV1001 can break tolerance as evidenced by prednisone responsive transaminitis. We have identified long-term survivors in each treatment cohort, and our preliminary data suggest that a combination of low dose doxorubicin, anti-CD20, KPT-9274 and RV1001 may be associated with the long-term survival. We have performed integrated genomic analysis of paired tumor/normal and matched constitutional samples from the 5 dogs in first cohort to identify candidate molecular correlates of treatment response. Matched tumor/normal whole genome sequencing confirmed previously described (TRAF3, SETD2, TP53) as well as novel candidate (MGA) driver mutations associated with canine DLBCL. Following completion of our pilot studies and correlative analyses, a large prospective study will be undertaken to confirm findings.
Exam offered and MVMA CE certificate issued following presentation.

Objectives

To understand the genomic landscape of canine diffuse large B cell lymphoma (DLBCL)
To understand how canine anti-CD20 can be used in the treatment of canine DLBCL
To understand how small molecule inhibitors can be combined with anti-CD20 and low dose chemotherapy to enhance outcomes in DLBCL.
Cheryl London

Author Information Play Video Bio

Cheryl London
on behalf of Missouri Veterinary Medical Association

Dr. Cheryl London is a Research Professor at Cummings School of Veterinary Medicine at Tufts University and the Molecular Oncology Research Institute at Tufts Medical Center. She has an active laboratory research program centered on comparative and translational oncology and is involved in the training of graduate students and postdoctoral fellows. Dr. London is also an Associate Faculty Professor at the Ohio State University College of Veterinary Medicine (OSU CVM) where she remains Director of the Clinical Trials Office at the CVM and Director of Translational Therapeutics at the Center for Clinical and Translational Sciences, OSU College of Medicine.

Current Accreditations

This course has been certified by or provided by the following Certified Organization/s:

  • Missouri Veterinary Medical Association
  • 0.25 Hours -
    Exam Attempts: 3
    -
    Exam Pass Rate: 60
  • Veterinary Cancer Society (VSC)
  • 0.25 Units

Faculty and Disclosures

Additional Contributors

Conflicts Declared

Conflicts of Interest declaration by Author:

null

User Reviews (0)

Go Back

Loading...


Saving changes...

Done

Error