A 2026 collection of nine clinical studies in the American Journal of Hematology highlights major shifts in lymphoma treatment across China, where annual disease incidence has reached 6.03 per 100,000 people. The published research demonstrates how circulating tumor DNA profiling, chemotherapy-free drug regimens, and targeted bispecific antibodies are reshaping subtype-specific management and stem cell transplantation strategies.
Lymphoma represents an expanding public health challenge in China, where incidence rates have steadily climbed over the past two decades. As clinical oncology teams meet this growing caseload, research programs across the country have pushed beyond conventional cytotoxic therapy into molecular diagnostics, cellular therapies, and targeted drug combinations.
Tracking Remissions and Relapse Risks With Liquid Biopsy ctDNA
Circulating tumor DNA, or ctDNA, is emerging as a sensitive instrument for evaluating therapy response, though its utility varies widely across tumor biologies. In a prospective multicenter evaluation of peripheral T-cell lymphoma (PTCL), blood-based ctDNA demonstrated a 75.2% sensitivity for genetic mutations that were simultaneously present in confirmed tumor tissue.
Tracking variant allele frequency and total ctDNA concentration gave clinicians an early window into progression-free survival and therapeutic response. When tumor-derived DNA fell during treatment cycles, disease control lasted longer.
Performance depended heavily on the underlying lymphoma subtype.
In angioimmunoblastic T-cell lymphoma (AITL), mutation detection sensitivity reached 82.1%. By contrast, detection dropped to 37.1% among patients with extranodal natural killer/T-cell lymphoma (NKTCL). The sharp disparity shows that circulating biomarkers cannot serve as a one-size-fits-all surveillance test across divergent lymphoma categories.
Location matters just as much as subtype. In primary central nervous system lymphoma (PCNSL), researchers evaluated patients receiving rituximab, high-dose methotrexate, and the BTK inhibitor orelabrutinib. Rather than relying on peripheral blood, investigators sampled cerebrospinal fluid.
Clearing ctDNA from the cerebrospinal fluid during active therapy correlated directly with complete remission and longer progression-free survival. The fluid test delivered higher predictive precision than interim PET/CT scans. Disappearance of MYD88 mutations in the central nervous compartment also pointed to superior outcomes, reinforcing the value of sampling directly within the biological sanctuary where tumor cells reside.
Chemotherapy-Free Regimens and Stem Cell Protocols in T-Cell and NK/T-Cell Subtypes
Because peripheral T-cell and natural killer cell lymphomas historically carry poor prognoses and limited therapeutic options, multiple Chinese trials evaluated novel regimens designed to bypass traditional cytotoxic combinations.
The phase II RCLARITY trial evaluating rituximab, lenalidomide, and chidamide tested a completely chemotherapy-free oral and targeted approach in relapsed or refractory AITL. The triple combination produced an overall response rate of 71.4% and a median overall survival of 17.6 months. Patients displaying clonal immunoglobulin rearrangement experienced more durable responses, though researchers noted that larger validation cohorts are required to confirm that genetic association.
Extranodal NK/T-cell lymphoma occurs far more frequently in East Asia than in Western nations, making regional protocol refinement an urgent priority. A retrospective study of 107 patients with advanced disease who achieved complete remission examined whether consolidation with autologous stem cell transplantation (ASCT) improved outcomes. Patients who underwent upfront ASCT achieved a 3-year progression-free survival rate of 78.2%, compared to 54.6% among those who did not undergo upfront transplantation.
That difference represents a marked gain in disease-free intervals, although the overall survival benefit lost statistical significance once investigators adjusted for other clinical variables.
Executing successful autologous transplantation depends on collecting sufficient stem cells, an obstacle for heavily pretreated individuals. A prospective trial of 140 Chinese patients classified as poor stem cell mobilizers evaluated rescue therapy with plerixafor and G-CSF. The regimen succeeded in 80.7% of participants, allowing them to collect the minimum threshold of 2 × 10^6 CD34+ cells/kg within four apheresis days.
For patients with NKTCL who exhaust immunotherapy, salvage paths have historically remained scarce. An analysis of 186 patients experiencing disease progression after immune checkpoint blockade recorded a median overall survival of 12.4 months. Resuming checkpoint inhibition in combination with other targeted agents achieved a 44.0% overall response rate and was independently linked to extended survival.
Glofitamab Bispecific Therapy as a Bridge to CAR-T in Aggressive B-Cell Cases
A critical therapeutic question in aggressive B-cell lymphomas centers on whether bispecific antibodies exhaust immune effector cells and diminish the efficacy of subsequent chimeric antigen receptor (CAR) T-cell therapy.
A real-world analysis of 64 Chinese patients with relapsed or refractory aggressive B-cell lymphoma evaluated salvage treatment with the CD20×CD3 bispecific antibody glofitamab before planned CAR-T administration. The glofitamab regimen produced an overall response rate of 78.7% and a complete response rate of 41.1%. At one year, the estimated progression-free survival stood at 61.3%, with an overall survival rate of 67.7%.
Prior exposure to the bispecific agent did not compromise subsequent CAR-T manufacturing or cell viability.
Laboratory correlative studies showed that patients who responded to glofitamab had higher baseline CD4+ effector T cells and showed greater early expansion of CD8+ T cells. These immune dynamics indicate that the underlying functional state of a patient’s immune system influences response to CD20×CD3 bispecifics and supports using the antibody as an effective bridge to cellular therapy.
| Subtype & Setting | Investigated Regimen | Primary Outcome Metric |
|---|---|---|
| Relapsed/Refractory AITL | Rituximab + Lenalidomide + Chidamide (RCLARITY) | 71.4% ORR; 17.6-month median OS |
| Advanced NKTCL in Complete Remission (107 patients) | Upfront Autologous Stem Cell Transplant | 78.2% vs 54.6% 3-year PFS |
| Post-Checkpoint Inhibitor NKTCL (186 patients) | Immunotherapy Retreatment Combinations | 44.0% ORR; 12.4-month median OS |
| R/R Aggressive B-Cell Lymphoma (64 patients) | Glofitamab Bridge to CAR-T | 78.7% ORR; 61.3% 1-year PFS |
Microenvironment Subtyping and Clinical Risk Profiles in Central Nervous System Lymphoma
Standard clinical staging frequently fails to capture early treatment failure in central nervous system presentations. To refine risk categorization, researchers integrated whole-genome sequencing with multiplex immunofluorescence in PCNSL cohorts.
By pairing tumor genomic architecture with spatial mapping of the surrounding immune microenvironment, investigators isolated an ultra-high-risk cohort representing 9.8% of the study population. Patients within this molecular subgroup experienced a median overall survival of only 3 months.
Identifying that aggressive biological profile early allows clinicians to separate patients who require experimental interventions from those likely to respond to standard methotrexate-based protocols. Similar biological risk-stratification models were also evaluated in patients aged 60 years or older with Hodgkin lymphoma, reflecting a broader clinical push across Chinese hematology centers to match therapy intensity directly to cellular behavior.