This is a prospective, multicenter Phase 2 clinical trial named the MALT-RO study, evaluating ultra-low-dose radiation therapy followed by orelabrutinib as first-line treatment for adults with Stage I-II MALT lymphoma. The study aims to determine the efficacy and safety profile of this sequential regimen. Eligible participants aged 18 years or older with histologically confirmed MALT lymphoma, measurable lesions, no prior systemic anti-lymphoma therapy, adequate organ function, and an ECOG performance status of 0-1 will receive 4Gy ultra-low-dose radiation (2Gy daily for 2 consecutive days) followed by oral orelabrutinib 150mg once daily for up to 6 cycles (28 days per cycle). Patients with partial response or stable disease after 6 cycles may continue orelabrutinib monotherapy for up to 12 cycles or until disease progression. All participants will undergo regular safety monitoring, tumor assessments, and long-term follow-up every 3 months to evaluate treatment durability. This treatment strategy is designed to improve efficacy and achieve more favorable outcomes compared with standard approaches for MALT lymphoma, while minimizing treatment-related toxicities such as long-term organ damage, xerostomia, cataracts, and other complications related to conventional standard-dose radiation, thereby offering a well-tolerated, convenient, targeted therapeutic option for patients with MALT lymphoma under strict ethical oversight in accordance with the Declaration of Helsinki and Chinese Good Clinical Practice guidelines.
Age ≥ 18 years, all genders eligible;
Histopathologically confirmed MALT lymphoma (extranodal marginal zone lymphoma) with at least one measurable lesion outside the spleen, with any diameter > 1.0 cm;
No prior systemic anti-tumor therapy after diagnosis (including chemotherapy, targeted therapy, rituximab, etc.).
ECOG performance status score of 0-1;
Current or history of other malignant tumors, except for those who have achieved complete remission after radical treatment;
Lymphoma involvement of the central nervous system or transformation to high-grade lymphoma;
Patients with other tumors who have not recovered from non-hematologic toxicities of prior anti-tumor therapy to ≤ Grade 1 (except for alopecia);
Congestive heart failure of New York Heart Association (NYHA) Class II or above, unstable angina, myocardial infarction within 6 months before the first dose of the study drug, or arrhythmias requiring treatment at screening, or left ventricular ejection fraction (LVEF) < 50%;
Single group
Orelabrutinib
DrugOrelabrutinib 150 mg tablets, administered orally once daily. Treatment consists of up to 6 consecutive 28-day cycles. Patients with partial response or stable disease without disease progression after 6 cycles may continue orelabrutinib monotherapy for up to 12 cycles.
Ultra-low-dose Radiation Therapy
RadiationThe total radiation dose is 4 Gy, administered as 2 Gy per day for 2 consecutive days.
Complete Remission Rate (CRR)
Complete remission is defined as the disappearance of all target lesions and no new lesions appearing, assessed per the Lugano Response Criteria for Lymphoma.
Incidence of Adverse Events
Safety outcomes include the incidence, severity, and relationship to treatment of all adverse events (AEs) and serious adverse events (SAEs) monitored throughout the treatment and follow-up period.
Objective Response Rate (ORR)
To evaluate the objective response rate (defined as the proportion of participants achieving complete remission \[CR\] or partial remission \[PR\]) in participants with Stage I-II MALT lymphoma treated with the sequential regimen, assessed per the Lugano Response Criteria.
Duration of Response (DOR)
To assess duration of response, defined as the time from the first documentation of objective response (CR or PR) to disease progression, recurrence, or death from any cause, per Lugano Response Criteria.
Time to Response (TTR)
To evaluate time to response, defined as the time from study enrollment to the first documentation of objective response (CR or PR), assessed per the Lugano Response Criteria.
Progression-Free Survival (PFS)
To assess progression-free survival, defined as the time from study enrollment to disease progression, recurrence, or death from any cause, per Lugano Response Criteria.
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Zhejiang Cancer Hospital
Lead sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborator
First Affiliated Hospital of Zhejiang University
Collaborator
Zhejiang Provincial People's Hospital
Collaborator
Zhejiang Provincial Tongde Hospital
Collaborator
Changxing County Traditional Chinese Medicine Hospital
Collaborator
