New Hope of CAR-T Cell Hodgkin’s Lymphoma Treatment
New Hope of CAR-T Cell Hodgkin’s Lymphoma Treatment
CAR-T cell therapy has emerged as a promising treatment for hematologic malignancies, but the targets approved by the US FDA for CAR-T cell therapy currently focus on CD19 and BCMA. CD30 is one of the hotspots under investigation. CD30 is present in various hematologic malignancies, with higher expression levels found in Hodgkin lymphoma, anaplastic large cell lymphoma, and other T-cell lymphomas and some B-cell non-Hodgkin lymphomas. Some antibody-drug conjugates (ADCs) or bispecific antibodies targeting CD30 have shown promising efficacy, but as these therapies are gradually applied as front-line treatments, there is still a need for alternative treatment options for consolidation therapy in refractory/relapsed patients after hematopoietic stem cell transplantation (HSCT).
Recently, The Lancet Haematology published the results of a phase 1 clinical trial indicating that CD30-targeted CAR-T cell therapy (ATLCAR.CD30) has the potential to serve as a consolidation treatment for high-risk Hodgkin lymphoma patients after autologous HSCT. Currently, 10%-25% of Hodgkin lymphoma patients have poor responses or relapse after front-line therapy, requiring further HSCT, and this trial proposed a new consolidation therapy approach.
Source: The Lancet Haematology
In this phase 1 study, 18 patients with relapsed high-risk CD30-positive lymphoma, including 11 cases of Hodgkin lymphoma, 6 cases of T-cell lymphoma, and 1 case of gray zone lymphoma, received CD30-targeted CAR-T cell therapy. Relapsed high-risk was defined as having refractory disease, relapse within 12 months of initial treatment, or extranodal involvement at the start of salvage therapy before transplantation. After preconditioning with the BEAM regimen (carmustine, etoposide, cytarabine, and melphalan) to eliminate tumor cells and prepare for normal hematopoietic stem cell engraftment, patients underwent hematopoietic stem cell transplantation and then received a single infusion of CAR-T cells as consolidation therapy, with a median time of 22 days from transplantation to infusion.
The primary endpoint was to determine the maximum tolerated dose. All patients were divided into three different dose groups, and since no dose-limiting toxicity was observed, the highest dose tested (2×108 CAR-T cells/m2) was determined as the maximum tolerated dose.
The study observed good safety and tolerability: no treatment-related deaths, no neurotoxicity, and no treatment discontinuations due to adverse events. One patient experienced grade 1 cytokine release syndrome. The most common grade 3-4 adverse events were lymphopenia (11%, 2/18 cases) and leukopenia (11%, 2/18 cases). Two patients developed secondary malignancies (non-small cell lung cancer and testicular cancer) approximately 2 and 2.5 years after treatment, respectively, but these were judged to be unrelated to the treatment.
This CAR-T cell therapy also demonstrated preliminary anti-tumor activity, particularly in Hodgkin lymphoma patients.
● With a median follow-up of 48.2 months after infusion, the median progression-free survival for all 18 patients was 32.3 months, and the median overall survival has not been reached and is still being accumulated.
● Among the 11 Hodgkin lymphoma patients, the 2-year progression-free survival rate was 73%, and the median progression-free survival has not been reached.
● The efficacy was less satisfactory in T-cell lymphoma patients, with 5 out of 6 patients relapsing.
● Due to having only 1 case, no conclusion could be drawn for the gray zone lymphoma patient.
The accompanying commentary article analyzed possible reasons for the poor efficacy in T-cell lymphoma. In this trial, 15 patients had previously received the CD30-targeted ADC therapy brentuximab vedotin, and studies have suggested that some patients may lose CD30 expression after brentuximab vedotin treatment. Additionally, case reports have indicated a link between CD30 expression loss and relapse after brentuximab vedotin and CD30-targeted CAR-T cell therapy. Unfortunately, this trial did not measure CD30 expression in patients after the completion of initial treatment, and this data may have helped elucidate the differences in efficacy. Furthermore, different preconditioning regimens may also affect CAR-T cell activity.
Overall, this study supports the promising anti-tumor activity and safety profile of CD30-targeted CAR-T cell therapy in Hodgkin lymphoma, and the accompanying commentary described the preliminary results as “very encouraging,” with anticipation for further studies to validate the potential of this approach.
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