New Agents in DLBCL Targeting Macrophages Stephen M. Ansell, MD, - - PowerPoint PPT Presentation

▶

new agents in dlbcl targeting macrophages

New Agents in DLBCL Targeting Macrophages Stephen M. Ansell, MD, - - PowerPoint PPT Presentation

Apr 29, 2023 202 likes •371 views

New Agents in DLBCL Targeting Macrophages Stephen M. Ansell, MD, PhD Professor of Medicine Chair, Lymphoma Group Mayo Clinic Peripheral blood monocyte numbers are associated with prognosis A. B. <570 <630 570 630 No. at

slide-1

SLIDE 1

New Agents in DLBCL – Targeting Macrophages

Stephen M. Ansell, MD, PhD

Professor of Medicine Chair, Lymphoma Group Mayo Clinic

slide-2

SLIDE 2

No. at risk

AMC low AMC high

No. at risk

AMC low AMC high <570 ≥570 ≥630 <630

A. B.

Peripheral blood monocyte numbers are associated with prognosis

Follicular lymphoma DLBCL

Wilcox et al. Leukemia. 2011 Sep;25(9):1502-9. Wilcox et al. Leuk Lymphoma. 2012 Apr;53(4):575-80.

slide-3

SLIDE 3

A.

HLADR HLA-DRlow (cells/μl) Ctrl NHL HLA-DR expression (MFI)

B. C. D.

Alone Untreated Mo IL-10 treated Mo CFSE CD14

CD14+HLA-DRlow monocytes are associated with immunosuppression

Xiu et al. Blood Cancer J. 2015 Jul 31;5:e328.

slide-4

SLIDE 4

A. B. C. D.

CD68 stain, 400X CD14 stain, 400X CD163 stain, 400X Merged image

Intratumoral monocytes have a different phenotype

slide-5

SLIDE 5

Follicular lymphoma Normal Large cell lymphoma

A C1 Density

CD14 SIRPα CD16 CD36 CD38 CD163 HLA-DR CD33 CD11c CD11b CD32

A. B.

B C D E E F G H F H G D E C B A

slide-6

SLIDE 6

A.

CD14 CD68 Lin

C. B. D.

CD163 CD14 CD14 SIRP α

slide-7

SLIDE 7

calreticulin

Mechanism of Phagocytosis

slide-8

SLIDE 8

Ansell SM et al, ASH 2016, #1812

A Phase 1 Study of TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies

slide-9

SLIDE 9

Ansell SM et al, ASH 2016, #1812

A Phase 1 Study of TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies

slide-10

SLIDE 10

Ansell SM et al, ASH 2016, #1812

A Phase 1 Study of TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies

slide-11

SLIDE 11

Ansell SM et al, ASH 2016, #1812

A Phase 1 Study of TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies

slide-12

SLIDE 12

Jan 2017 Dec 2016 Nov 2016 SIRPa-Fc + Rituximab Initial Dx – transformed lymphoma

Ansell SM et al, ASH 2016, #1812

A Phase 1 Study of TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies

slide-13

SLIDE 13

Adults with solid tumors - Part A to determine the optimal Priming

Dose, Part B to determine the optimal Maintenance Dose.

16 patients have been enrolled, 11 in Part A and 5 in Part B.
In Part A, 1 mg/kg dose was selected as the Priming Dose.
In Part B, the study is ongoing with the current cohort at 1 mg/kg

followed by 10 mg/kg weekly.

Hu5F9-G4-related AEs - anemia (11 G1, 5 G2), hyperbilirubinemia

(5 G1, 3 G2, 1 G3), headache (9 G1, 1 G2), nausea (3 G1), and retinal toxicity (1 G2).

Most AEs were associated with the Priming Dose and were

reversible.

Two patients (adenoid cystic ca) had stable disease for 16 and 8

months.

First-in-human, first-in-class phase I trial of the anti-CD47 antibody Hu5F9-G4 in patients with advanced cancers

Sikic et al. J Clin Oncol 34, 2016 (suppl; abstr 3019)

slide-14

SLIDE 14

Targeting CD47/SIRPα in Lymphoma

slide-15

SLIDE 15

Acknowledgements

Lab members -

Zhi-Zhang Yang Hyo Jin Kim Ya-Ping Chen Tammy Price Troska JC Villasboas Anne Novak

Grant funding –

National Institutes of Health, Leukemia & Lymphoma Society, Lymphoma Research Foundation, Predolin Foundation.