Seattle Cellular Therapy Summit 2026

PUTTING IT INTO PRACTICE A Practical Decision Framework No single “right answer” — patient and disease factors should guide the choice Favor cilta-cel when... • CD38 antibody–exposed or –refractory disease • High-risk cytogenetics, incl. gain/amp(1q) • Patient values a treatment-free interval / one-time therapy • Fit for apheresis, bridging therapy, and inpatient monitoring • Timely access to a certified CAR-T center Favor tec-dara when... • Frail or older patient, or limited CAR-T-center access • CD38-naive or CD38-sensitive disease • Rapid treatment start needed — manufacturing delay unacceptable • Patient can manage ongoing dosing & monitoring visits • Community-based care strongly preferred Shared considerations, regardless of choice Plan infection prophylaxis proactively either way; discuss goals of care and QOL preferences directly with the patient; consider trial enrollment (e.g., time-limited dosing strategies) when available; and involve a CAR-T–capable center early in the discussion, even if a bispecific is chosen first — to keep both options open for the future. Synthesized from San-Miguel J et al., Costa LJ et al., Banerjee R, and Janakiram M.

Persistent CAR T Expansion or Malignant Transformation? Feature | IEC-associated enterocolitis | Secondary CAR+ T cell lymphoma CAR+ T cells in biopsy | Expected | Expected Dominant TCR clone | Can occur | Usually present CD8+ cytotoxic phenotype | Can occur | Can occur Villous blunting/apoptosis | Can occur | Can occur Clonal persistence | May occur | Usually persistent Additional oncogenic mutations | Rare | Frequently identified Progressive genetic evolution | Not expected | Characteristic Final diagnosis: Indolent CAR+ T-cell lymphoma of the GI tract

Summary – Myeloma in 2030 • Paradigms we need to move away from: • Auto transplant upfront for everyone • Automatic high dose dexamethasone for all regimens • Indefinite maintenance • Where do we need to go? • Upfront, time limited bispecific antibody or CAR T • Investment in local manufacturing, regulatory changes to improve global access • Recognition of MRD status as a legitimate, clinically actionable endpoint for clinical care

The next generation of CAR-T for myeloma • Better engineering • Deep and durable responses • Fewer severe and delayed neurologic toxicities • Faster manufacturing (AZD0120) • Novel targets • Expanding beyond BCMA (GPRC5D) • Earlier treatment • Testing CAR-T as an alternative to upfront ASCT • Remaining questions • Are outcomes superior to current CAR-T? • Will dual-targeting reduce relapse? • What is the optimal sequencing with bispecific antibodies? • Which patients should receive which CAR-T

Interim analysis of LimiTEC, a prospective trial of limited-duration teclistamab for relapsed/refractory multiple myeloma Beatrice Razzo, Rajshekhar Chakraborty, Hira Shaikh, … Alfred Garfall (Thomas Jefferson; Columbia; Iowa; Penn; MSK; Harvard; Lehigh Valley; Arkansas) References: 1. Razzo B. Blood 2025. 2. Garfall A. ASCO 2024.

OBX-115 Mechanism of Action ACZ-regulated mbIL15 activates OBX-115 and other immune cells [Diagram, labels as shown: Patient → Tumor → Isolated TIL → viral transduction of mbIL15-DRD transgene → OBX-115. ACZ ligand: basal state (unstable DRD, degraded mbIL15, proteasome) → ON state (ACZ-stabilized DRD, surface mbIL15). Cis-activation (IL2Rβ/IL2Rγ) + trans-activation of immune cells → direct killing of tumor cells; antigen-independent expansion & persistence; memory TIL. ACZ eliminates need for IL2.] ACZ, acetazolamide; DRD, drug-responsive domain; IL2, interleukin 2; mbIL15, membrane-bound interleukin 15; TIL, tumor-infiltrating lymphocytes. Allison Betof, ASCO 2026

VCAR33 • CD33 CAR-T after Allogeneic HCT • N=15 patients • Grade 3-4 CRS in 0 patients • Grade 3-4 GVHD in 1 patient • Grade 3 ICANs in 1 patient • ORR 20% • Study closed prior to completion [Right panel partially out of frame: “VCAR33, a Donor-d… for AML Relaps…” — Mushtaq et al.; footer citation: Mushtaq. Blood. 2025.]