The 18th International Conference on Malignant Lymphoma (ICML), organized by the Institute of Oncology Research (IOR), was held from June 17 to 21, 2025, in Lugano, Switzerland. As the most influential biennial event in hematologic oncology, ICML 2025 brought together over a thousand hematologists, clinical oncologists, and lymphoma experts from around the world to explore the latest insights into disease mechanisms, translational medicine, and clinical innovation.Among the featured speakers, Prof. Qingqing Cai and her team from Sun Yat-sen University Cancer Center delivered a keynote presentation in the “Radiotherapy in Lymphoma” session on optimal systemic therapy strategies for extranodal nasal-type NK/T-cell lymphoma (ENKTCL). In addition, they presented new findings from an ongoing phase Ib/II multicenter, open-label study evaluating linperlisib combined with CHOP (L-CHOP) in treatment-naïve peripheral T-cell lymphoma (PTCL) patients (Abstract #165). In an exclusive interview with Oncology Frontier – Hematology Frontier, Prof. Cai shared insights on the clinical relevance and innovation behind these regimens.Current Systemic Strategies and Emerging Therapies in ENKTCL
Oncology Frontier – Hematology Frontier: What are the current frontline systemic therapies for ENKTCL in China and abroad? How do these treatments differ by stage? Have there been breakthroughs for relapsed/refractory cases?
Prof. Qingqing Cai: Extranodal nasal-type NK/T-cell lymphoma (ENKTCL) is a highly aggressive subtype of non-Hodgkin lymphoma that typically presents in extranodal sites such as the nasal cavity. It is molecularly heterogeneous and clinically distinct from other lymphomas, with variable treatment responses and prognoses across patient populations.
Commonly used frontline regimens include P-GEMOX (pegaspargase + gemcitabine + oxaliplatin), DDGP (dexamethasone + cisplatin + gemcitabine + pegaspargase), AspaMetDex (L-asparaginase + methotrexate + dexamethasone), and the modified SMILE regimen. At our center, we developed the P-GEMOX protocol, which has achieved 5-year survival rates of 70–80% in early-stage ENKTCL, with favorable tolerability and ease of administration.
We further explored combining P-GEMOX with PD-1 blockade using toripalimab, launching the world’s first phase III randomized trial comparing P-GEMOX plus toripalimab followed by radiotherapy versus P-GEMOX with radiotherapy alone. The outcomes of this study are highly anticipated.
For advanced-stage ENKTCL, P-GEMOX monotherapy has a CR rate of 43%, but 2-year PFS and OS rates remain suboptimal (32% and 45%, respectively). To address this, we introduced PD-1 inhibitor sintilimab into the regimen, which led to striking results in the phase II SPIRIT study—raising the CR rate to 85%, with 2-year PFS and OS improving to 64% and 91%, respectively. These results have been incorporated into the 2025 ESMO-EHA PTCL treatment guidelines. We are now validating these findings in the phase III SPIRIT-02 trial.
Relapsed/refractory (R/R) ENKTCL remains challenging, with median OS around 6 months. Innovative therapies are urgently needed. Recent advances include immunotherapy, nanomedicine, and targeted treatments. Immune checkpoint inhibitors (e.g., anti–PD-1/PD-L1 antibodies) have demonstrated efficacy in activating tumor-reactive T cells. Nanodrug PLM60 (mitoxantrone liposome) offers improved tumor targeting and reduced toxicity. We are currently evaluating PD-1 inhibitors combined with PLM60 in R/R ENKTCL.
Moreover, we are exploring targeted agents against aberrant signaling in ENKTCL, such as the JAK inhibitor golidocitinib, the PI3K inhibitor linperlisib, and the HDAC inhibitor chidamide—each showing potential to overcome conventional treatment limitations.
L-CHOP: A New First-Line Option for PTCL
Oncology Frontier – Hematology Frontier: In the LINCH trial, your team is investigating linperlisib plus CHOP (L-CHOP) for newly diagnosed PTCL. What is the rationale for this combination, and how does it improve upon existing therapies?
Prof. Qingqing Cai: Peripheral T-cell lymphoma (PTCL) is a heterogeneous and aggressive group of non-Hodgkin lymphomas. The standard CHOP regimen has limited efficacy, with CR rates around 30% and poor long-term survival, prompting the need for more effective frontline options.
Linperlisib is a selective PI3Kδ inhibitor that has demonstrated promising responses in R/R PTCL. Based on its activity, we combined it with CHOP to create the L-CHOP regimen, aiming to enhance response rates and survival in newly diagnosed patients through a precision-targeted approach.
The LINCH trial is a multicenter, single-arm phase Ib/II study enrolling 28 patients between August 2023 and October 2024. After six cycles of combination therapy, patients in response receive linperlisib maintenance. As of March 2025, 53.6% (15/28) achieved complete remission (CR), and the overall response rate (ORR) was 67.9% (19/28). Best ORR reached 92.9% (26/28), with a best CR rate of 57.1% (16/28). While hematologic toxicities such as neutropenia and thrombocytopenia were observed, most were manageable with no unexpected severe adverse events.
These results offer new hope for patients with aggressive PTCL and poor prognosis. The study is ongoing, and we are optimistic about the final outcomes.
Breakthrough Directions from ICML & EHA 2025
Oncology Frontier – Hematology Frontier: With major international meetings like EHA and ICML recently held, what research directions do you believe have the potential to reshape lymphoma care? Could you share a standout study from these conferences?
Prof. Qingqing Cai: The 2025 conference season has been rich in innovation. We’re witnessing a shift in lymphoma treatment strategies—driven by multi-omics analysis and a focus on clinically relevant mechanisms. This paradigm connects molecular biology to actionable therapies.
One presentation I’m particularly looking forward to is the EHA oral session on tumor cell mapping in EBV-driven ENKTCL, analyzed through multi-omics approaches. I expect this study to enhance our understanding of disease progression and inform new therapeutic targets.
At ICML, I will be presenting on June 17 (16:15 local time), highlighting new treatment strategies for ENKTCL and reviewing advances from leading global research groups to support personalized care.
Among drug innovations, bispecific antibodies are leading the charge. Epcoritamab, a subcutaneous CD3/CD20 bispecific antibody, has shown strong efficacy in relapsed/refractory DLBCL by enhancing complete response rates.
We’re also seeing progress in targeting epigenetic dysregulation. The oral EZH2 inhibitor SHR2554 has shown promising efficacy in R/R PTCL.
In cell therapy, CD19/CD20 dual-targeted CAR-T cells are gaining momentum, offering new solutions for patients with CD19 antigen escape—addressing a key limitation of earlier CAR-T treatments.
Expert Profile: Prof. Qingqing Cai
- Affiliation: Sun Yat-sen University Cancer Center
- Positions:
- Deputy Director, Department of Internal Medicine
- Principal Investigator, Lymphoma Unit
- Vice President, Sun Yat-sen University Cancer Center Gansu Branch
- Chief of Hematology
Titles:
- Changjiang Distinguished Professor, Ministry of Education
- Chair, Lymphoma Committee, Chinese Anti-Cancer Association (Integrative Medicine Section)
- Chair, Lymphoma Committee, Guangdong Anti-Cancer Association
- Chair, Lymphoma Committee, Guangdong Precision Medicine Society
- Vice Chair, Lymphoma Committee, CSCO
- Vice Chair, Lymphoma Committee, Chinese Association of Geriatric Health Care
Research Contributions:
- Over 20 SCI papers published in high-impact journals including Lancet Haematology, Blood, Signal Transduction and Targeted Therapy, Clinical Cancer Research, and Leukemia (as corresponding or co-corresponding author)
- Principal investigator on five National Natural Science Foundation of China (NSFC) grants, including one key project
- Winner of the 2023 Guangdong Provincial Science and Technology Progress Award (First Prize)
- Named one of the “Top Ten Elite Medical Experts” at the 2022 National Medical Scientists Annual Meeting
