The 18th International Conference on Malignant Lymphoma (18-ICML), hosted by the Institute of Oncology Research (IOR), was held from June 17–21, 2025, in Lugano, Switzerland. As one of the world's leading academic events in hematologic oncology, ICML 2025 gathered thousands of hematologists, clinical oncologists, radiation oncologists, and basic researchers from across the globe to deeply explore lymphoma pathogenesis, translational breakthroughs, and innovations in clinical management.At the conference, Professor Lu-Gui Qiu from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, presented the results of a Phase I/II clinical trial investigating the safety and efficacy of igemotostat, a novel EZH2 inhibitor, in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL). The study offered promising new treatment options for challenging subtypes such as follicular lymphoma (FL) and peripheral T-cell lymphoma (PTCL).
In an exclusive interview with Oncology Frontier – Hematology News, Professor Qiu provided an in-depth analysis of the study’s clinical significance, its applicability across lymphoma subtypes, and future combination strategies, aiming to inspire new therapeutic approaches in clinical practice.
Oncology Frontier – Hematology Frontier: The data presented show that igemetostat achieved a remarkable ORR of 66.7% and a DCR of 100% in the R/R follicular lymphoma (FL) cohort. From your perspective, how does this efficacy compare with existing treatments? What potential improvements might this bring to survival outcomes and quality of life for patients with R/R FL?
Prof. Lu-Gui Qiu: At this year’s ICML, we presented the latest results from a Phase I clinical trial of the novel, highly selective EZH2 inhibitor igemetostat, targeting relapsed/refractory non-Hodgkin lymphoma (R/R NHL). The data included an integrated analysis of both the dose-escalation and dose-expansion phases. As of December 18, 2024, a total of 120 patients had been enrolled. Among them, 19 patients participated in the dose-escalation phase, and efficacy was evaluable in 16. Across diverse NHL subtypes—both B-cell and T-cell origin—the ORR was 56.3%, and DCR reached 87.5%, providing a solid foundation for further exploration in the dose-expansion phase.
The dose-escalation used a 3+3 design with accelerated titration, testing six dose levels (100–2000 mg orally twice daily, 28-day cycles). Based on these findings, 1200 mg BID was established as the recommended Phase II dose (RP2D). At this dose, the ORR among all FL patients reached 66.7%. Notably, subgroup analysis revealed that both EZH2-mutant and wild-type patients showed deep responses—ORR was 70.0% in the mutant group and 63.2% in the wild-type group, with DCR close to 100%. Median PFS was 10.8 months, median duration of response (DOR) 7.4 months, and the overall survival (OS) data have not yet matured. Even among the poor-prognosis subgroup with progression within 24 months (POD24), ORR remained strong at 56.5%.
Compared to existing options, igemetostat offers unique clinical advantages. For instance, linperlisib, a domestically developed PI3K inhibitor, is another approved therapy for R/R FL in China. Its ORR in ≥3rd-line treatment is reported at 79.8%, with a CR rate of 15.5%, PR of 64.3%, and median PFS of 13.4 months. However, due to safety concerns, PI3K inhibitors have been largely withdrawn from use in FL and PTCL treatment internationally. Linperlisib continues to be used in China due to its favorable efficacy and manageable toxicity. That said, most patients eventually develop resistance or relapse with small molecule inhibitors. Encouragingly, in our study, igemotostat demonstrated efficacy even in patients previously treated with PI3K inhibitors, BTK inhibitors (e.g., zanubrutinib/orelabrutinib), CD19 CAR-T cells, or autologous stem cell transplant.
These findings support the safety and efficacy of igemetostat in heavily pretreated R/R FL patients, with over two-thirds achieving at least a partial response. This introduces a promising new treatment option for this difficult-to-treat population. Looking ahead, we aim to explore combination strategies—including small molecule targeted agents with chemoimmunotherapy or bispecific antibodies—to deepen responses and further improve long-term, high-quality survival for patients.
Oncology Frontier – Hematology Frontier: Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous disease, with varying treatment challenges and prognoses across subtypes. Given that igemetostat has shown significant efficacy in multiple PTCL subtypes such as PTCL-NOS and AITL, do you believe this suggests broad applicability in R/R PTCL? For future studies on R/R PTCL, what key areas should be prioritized to further validate its efficacy and safety?
Prof. Lu-Gui Qiu: Our findings demonstrate that igemetostat provides encouraging clinical benefit and safety in relapsed/refractory peripheral T-cell lymphoma (R/R PTCL). In the dose-expansion phase, a total of 58 PTCL patients were enrolled, and at the RP2D level, the overall response rate (ORR) exceeded 70%. With a median follow-up of 14.7 months, the median progression-free survival (mPFS) reached 15.7 months, and median duration of response (mDOR) was 13.9 months; median overall survival (mOS) has not yet been reached.
Subgroup analysis revealed homogeneous efficacy across the two major pathological subtypes—angioimmunoblastic T-cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS)—regardless of whether patients received 800 mg or 1200 mg dosing. The ORRs for AITL and PTCL-NOS were 68.2% and 72%, respectively, with comparable mPFS and mDOR outcomes. Given that PTCL is a prototypically aggressive lymphoma with a much poorer prognosis than B-cell-derived DLBCL (where 5-year survival post–first-line treatment can reach 50–70%), these findings represent a meaningful advancement. Most PTCL patients relapse after standard first-line therapy and face limited options thereafter.
The study results presented at ICML 2025 offer new hope for improving outcomes in this difficult-to-treat population. Compared to current agents such as the HDAC inhibitor chidamide, the PI3K inhibitor linperlisib, and the JAK1 inhibitor golidocitinib, which have achieved monotherapy ORRs around 50–60% in R/R PTCL, igemetostat appears to offer superior efficacy. The drug has now entered pivotal registration trials as monotherapy, and its regulatory progress is highly anticipated.
For future studies, it will be important to further examine long-term survival outcomes, biomarker-driven stratification, and combinatorial strategies involving immunotherapy or other novel agents to maximize response depth and durability in PTCL.
Oncology Frontier – Hematology Frontier: Based on the current findings, how do you see the treatment landscape for non-Hodgkin lymphoma (NHL) evolving? What combination strategies could be considered to further enhance efficacy or benefit specific patient populations?
Prof. Lu-Gui Qiu: Although small-molecule targeted therapies have made notable advances in the treatment of aggressive lymphomas, monotherapies still frequently encounter issues such as drug resistance and relapse. To overcome these challenges, our research team is actively exploring combination strategies.
On one front, preclinical screening is being used to identify synergistic targeted therapy combinations. Several related clinical trials have already been launched to evaluate the safety and efficacy-enhancing potential of combining the EZH2 inhibitor igemetostat with agents such as the HDAC inhibitor chidamide, PI3K inhibitor linperlisib, and JAK1 inhibitor golidocitinib. These studies aim to identify the most promising combinations that could proceed to larger confirmatory trials.
On another front, we are also investigating the use of small-molecule agents in combination with traditional chemotherapy as a first-line treatment, not just in relapsed/refractory settings. For example, our team is currently leading a Phase III head-to-head clinical trial comparing linperlisib plus CHOP versus standard CHOP in previously untreated PTCL patients. The trial is progressing well, and results are expected within the next 2–3 years. We hope this approach will help improve long-term remission rates and overall survival in the frontline setting.
Expert Profile
Chief Clinical Expert, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
- Chief Physician, Doctoral Supervisor
- Director, Tianjin Cord Blood Hematopoietic Stem Cell Bank
- Recipient of the State Council Special Government Allowance
- National Health Commission Distinguished Young and Middle-Aged Expert
- Member, International Myeloma Society (IMS)
- Committee Member, International Myeloma Working Group (IMWG)
- Editorial Board Member, Blood Advances
- Honorary Chairman, Hematologic Oncology Committee, Chinese Anti-Cancer Association
- Vice Chairman, Lymphoma Expert Committee, Chinese Society of Clinical Oncology (CSCO)
- Vice Chairman, Hematology Institutions Branch, Chinese Hospital Association
- Vice Chairman, Hematology Professional Committee, Chinese Medical and Pharmaceutical Education Association
- Vice President, 6th Council of Tianjin Anti-Cancer Association
- Editorial board member of 6 core journals including Chinese Journal of Hematology
Professor Qiu has led over 30 national-level research projects, including key programs of the National Science and Technology Support Plan and major grants from the National Natural Science Foundation.
He has authored nearly 500 academic papers, including over 150 SCI-indexed publications, edited five medical monographs, and holds five national invention patents.
He has received two first prizes for provincial and ministerial-level scientific achievements.
