Anti-CD30 CAR T-cell consolidation after auto-HSCT in patients with high-risk CD30+ lymphoma: results from a phase I trial

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard of care for patients with relapsed Hodgkin lymphoma.¹ There is a need for alternative consolidation strategies after auto-HSCT in patients at a high risk of relapse. As previously covered by the Lymphoma Hub, anti-CD30 chimeric antigen receptor (CAR) T-cell therapy could be a promising posttransplant consolidation therapy for patients with CD30⁺ Hodgkin and non-Hodgkin lymphoma who are at high risk of relapse.¹

Recently, results were published from a phase I trial (NCT02663297) assessing the safety of anti-CD30 CAR T-cell therapy as consolidation after auto-HSCT in patients with high-risk CD30⁺ lymphoma by Grover et al. in The Lancet Haematology. We summarize the key findings below.

Study design and patient population¹

• Multicenter, single-arm, phase I dose escalation trial.
• Included patients aged ≥3 years with relapsed high-risk classical Hodgkin lymphoma or CD30⁺ non-Hodgkin lymphoma who were eligible for high-dose chemotherapy and auto-HSCT.
• Patients underwent conditioning with carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by auto-HSCT.
• Patients received a single dose of CAR T-cells at one of three dose levels:
  • Dose level 1: 2 × 10⁷ cells/m²
  • Dose level 2: 1 × 10⁸ cells/m²
  • Dose level 3: 2 × 10⁸ cells/m²
• The primary endpoints were the maximum tolerated dose of CAR T-cells, safety, and tolerability.
• Secondary endpoints included progression-free survival and overall survival.

Key findings¹

Patient characteristics

• In total, 18 patients received treatment, of which 11 had Hodgkin lymphoma, six had T-cell lymphoma, and one had grey zone lymphoma.
• The median age was 43 years (range, 16–76 years).
• Four, five, and nine patients were treated at Dose levels 1, 2, and 3, respectively.

Safety

• No dose-limiting toxicities were observed; Dose level 3 was established as the maximum tolerated dose
• No treatment-related deaths occurred.
• One patient treated at Dose level 3 experienced Grade 1 cytokine release syndrome (Table 1).

Table 1. Treatment-emergent adverse events*

Treatment-emergent adverse events, n	Grade 1–2	Grade 3	Grade 4
*Adapted from Grover, et al.1
Anemia	1	1	0
Aspartate aminotransferase increased	4	0	0
Cytokine release syndrome	1	0	0
Diarrhea	3	0	0
Dizziness	2	0	0
Fatigue	3	0	0
Headache	2	0	0
Hypocalcemia	2	0	0
Lymphocyte count decreased	6	2	0
Nausea	6	0	0
Neutrophil count decreased	3	0	1
Platelet count decreased	4	1	0
Rash maculopapular	1	1	0
Vomiting	2	0	0
White blood cell count decreased	4	2	0

Efficacy

• After a median follow-up of 48.2 months, 44% of patients relapsed (Dose level 1, n = 3; Dose level 2, n = 1; Dose level 3, n = 4).
• Median progression-free survival was 32.3 months and not reached for all treated patients and patients with Hodgkin lymphoma, respectively.
• The median overall survival was not reached for all treated patients.
• The 2-year survival rates are shown in Figure 1.
• All patients with Hodgkin lymphoma are alive, while five patients with T-cell lymphoma have died (relapse, n = 4; unrelated lung cancer, n = 1).

*Adapted from Grover, et al.

 

Key learnings

Results from this trial suggest that consolidation with anti-CD30 CAR T-cells following BEAM and auto-HSCT is feasible in patients with CD30+ lymphoma who are at high risk of relapse. Treatment was well-tolerated, and preliminary clinical activity was observed in patients with Hodgkin lymphoma. Future trials are needed to compare this approach with maintenance therapy with brentuximab vedotin or checkpoint inhibitors.