A 100% Response Rate: How European Researchers Are Rewriting the Rules for Refractory Lymphoma Treatment
For patients battling relapsed or refractory Hodgkin lymphoma and T-cell lymphoma, hope has often been a scarce commodity. But a groundbreaking Phase I clinical trial in Europe is changing that narrative. Researchers have achieved a remarkable 100% overall response rate with a novel CAR-T cell therapy, HSP-CAR30, offering a potential lifeline to those who have exhausted conventional treatment options. This isn’t just incremental progress; it’s a potential paradigm shift in how we approach these aggressive cancers.
The Challenge of CD30+ Lymphomas and the Promise of CAR-T Therapy
Hodgkin lymphoma and other CD30+ lymphomas present a significant clinical challenge, particularly when they return after initial treatment or prove resistant to standard therapies. While CAR-T cell therapy – engineering a patient’s own immune cells to target cancer – has revolutionized treatment for certain blood cancers like B-cell leukemia, its application to CD30+ lymphomas has been hampered by a critical issue: the modified T cells often don’t persist long enough to maintain a lasting anti-cancer effect. This lack of durability has led to high relapse rates, limiting the therapy’s potential.
HSP-CAR30: A New Generation of CAR-T Cells
The team at the Sant Pau Research Institute (IR Sant Pau) in Barcelona, led by Dr. Javier Briones, tackled this challenge head-on. Their innovation, **CAR-T cell therapy** HSP-CAR30, isn’t just another iteration of existing technology. It’s a carefully optimized version designed for enhanced functionality and, crucially, longevity. Researchers focused on targeting a more stable region of the CD30 protein, preventing the cancer from evading attack by shedding the protein. This strategic approach, combined with a refined manufacturing process, is yielding impressive results.
Boosting Persistence with Memory T Cells
A key finding from the Phase I trial, published in the prestigious journal Blood, is the high in vivo persistence of CAR30+ cells – they remained detectable in 60% of patients a year after infusion. This persistence isn’t just about quantity; it’s about quality. The therapy promotes the expansion of central memory T cells (TCM) and stem-like memory T cells (TSCM-LIKE), which are known to be crucial for long-term immune responses and sustained remission. As Dr. Briones explains, this persistence translates to a “real and lasting impact on the disease.”
Phase I Results: A Glimpse of Hope
The Phase I trial involved ten patients with relapsed or refractory classical Hodgkin lymphoma or CD30+ T-cell lymphoma. The results were striking: a 100% overall response rate and a 50% complete remission rate. Even more encouraging, 60% of patients who achieved complete remission remained in remission after a median follow-up of 34 months. Importantly, the treatment demonstrated a favorable safety profile, with only mild and manageable side effects – primarily Grade 1 cytokine release syndrome (CRS) – and no neurotoxicity observed.
Phase II Expansion and Future Directions
Building on this success, the study has progressed to a Phase II trial, now involving 42 patients. Preliminary data from Phase II, presented at the 2024 American Society of Hematology (ASH) meeting, show that over 55% of patients have achieved complete remission. This expansion is crucial for strengthening the robustness of the findings and paving the way for broader clinical application. The study is registered on ClinicalTrials.gov (NCT04653649).
Beyond Hodgkin Lymphoma: Expanding the Reach of CD30-Targeted Therapy
While the initial focus is on Hodgkin lymphoma and CD30+ T-cell lymphoma, the potential of HSP-CAR30 extends beyond these specific cancers. The CD30 protein is also expressed in other malignancies, suggesting that this therapy could be adapted to treat a wider range of CD30-positive tumors. Researchers are actively exploring these possibilities.
The European Lead and the Future of CAR-T Manufacturing
HSP-CAR30 represents a significant milestone as the first European CAR-T30 study to successfully complete its initial phase. This achievement underscores Europe’s growing role in the development of advanced cancer therapies. The success of the Sant Pau project also highlights the importance of dedicated funding and infrastructure. The Josep Carreras Leukaemia Foundation played a pivotal role, investing over two million euros and establishing a state-of-the-art cell production facility – “The Unstoppable Cell Factory” – to support the trial.
The advancements made in optimizing CAR-T cell manufacturing, particularly the innovative strategy of combining interleukin-21 (IL-21) with IL-7 and IL-15 to promote the expansion of long-lived memory T cells, are likely to influence the development of CAR-T therapies for other cancers as well. This focus on enhancing T cell persistence is becoming a central theme in the field.
What are your predictions for the future of CAR-T therapy and its impact on cancer treatment? Share your thoughts in the comments below!