CD30 CAR-T IN RELAPSED AND REFRACTORY CD30+ LYMPHOMAS: LONG-TERM FOLLOW-UP OF A PHASE IB/II CLINICAL TRIAL

Abstract

Introduction: CD30 CAR-T is active and safe in relapsed/refractory (r/r) CD30⁺ lymphomas, including classic Hodgkin lymphoma (cHL) and mature T-cell lymphomas (MTCLs). Here, we share long-term follow-up from our phase Ib/II trial (NCT02690545).

Methods: Following cell procurement and CD30 CAR-T manufacturing, patients (pts) received lymphodepletion (LD) followed by CAR-T infusion. Pts could receive bridging between procurement and LD. Two dose levels were assessed in a 3+3 design: 1x10⁸ CAR⁺ cells/m² (DL1) and 2x10⁸ CAR⁺ cells/m² (DL2). Once dose escalation was completed in adults, children were enrolled on the phase Ib portion. Inclusion criteria include r/r CD30⁺ lymphoma after ≥ 2 therapies and Karnofsky/Lansky performance status > 60%. LD was initially bendamustine (benda) 90 mg/m²/day on days −5 to −4, but was changed to fludarabine (flu) 30 mg/m²/day and benda 70 mg/m²/day on days -5 to -3 for efficacy.

Results: 34 pts received CD30 CAR-T 1/10/2017 to 3/11/2024, including 29 with cHL and 4 with MTCLs (ALK⁺ ALCL, enteropathy-associated T-cell lymphoma, primary cutaneous ALCL, and Sézary syndrome). Median age was 33 (range 10–68) for cHL and 31 (11–70) for MTCL. The median number of prior lines of therapy was 5 (2–18) in cHL and 4 (2–6) in MTCL. Bridging therapy (new therapy started between procurement and CAR-T infusion) was used in 15 cHL and 3 MTCL pts. In cHL pts, prior therapies—including bridging—included brentuximab vedotin (n = 28), PD-1 inhibitor (PD-1i, n = 23), bendamustine (n = 18), autologous stem cell transplant (SCT, n = 24), and alloSCT (n = 10). At LD, 24 cHL and 4 MTCL pts had active disease (PR or worse) and were evaluable for response to CAR-T. 8 pts with cHL received benda LD; all others received flu/benda LD. Median vein-to-vein time (time from procurement to CAR-T infusion) was 84 days (40–337). 7 pts with cHL and 2 with MTCL were treated on DL1; all others on DL2.

In cHL pts, the CR rate with benda LD was 0/5; it was 15/19 with flu/benda LD. 2/4 pts with MTCL achieved CR.

Median follow-up was 6.6 years for cHL and 6.0 years for MTCL. For cHL, 6-year progression-free survival (PFS) was 19% (80% CI: 11–32), 6-year duration of response (DOR) was 25% (80% CI: 15–41), and 6-year overall survival (OS) was 84% (80% CI: 73–96) (Figure 1A–C). For MTCL, 6-year PFS was 50% (80% CI: 26–95), 6-year DOR was 67% (80% CI: 40–100), and 6-year OS was 67% (80% CI: 40–100) (Figure 1D–F). In pts with cHL, Flu/benda LD (HR: 0.47, 80% CI 0.26–0.85) and PD-1i ≤ 1 year before CAR-T (HR: 0.44, 80% CI: 0.25–0.79) were associated with superior PFS, whereas increasing lines of therapy and prior alloSCT were associated with inferior PFS (Figure 1G).

Conclusions: CD30 CAR-T has encouraging activity and maintains durable responses in a heavily pretreated population with cHL and CD30⁺ MTCLs. As previously reported, fludarabine-based LD is critical for its efficacy. Our group continues exploring the beneficial impact of PD-1i on CD30 CAR-T outcomes.

Research funding declaration: This work was supported by funding from the National Institutes of Health (UNC-Integrated Translational Oncology T32-CA244125 to UNC/DKR)

Keywords: cellular therapies; aggressive T-cell non-Hodgkin lymphoma; Hodgkin lymphoma

Potential sources of conflict of interest:

J. Serody

Other remuneration: Carisma Therapeutics, Merck Inc. Glaxo Smith Klein, PIQUE Therapeutics, Triangle Biotechnology

G. Dotti

Consultant or advisory role: Bellicum Pharmaceuticals, Catamaran Bio, Estrella

N. Grover

Honoraria: Regeneron Pharmaceuticals, Novartis, BMS, Caribou, Janssen, Kite

Other remuneration: Sangamo