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1622 Zanubrutinib, Lenalidomide, Rituximab, Temozolomide and Methotrexate (RLZT±MTX) As First-Line Treatment for Newly Diagnosed PCNSL: A Prospective, Open-Lable, Multicenter Clinical Trial

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster I
Hematology Disease Topics & Pathways:
Combination therapy, Therapies
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Jia Song1*, Hui Liu2*, Zongjiu Jiao3*, Da Gao4*, Kai Ding1*, Yihao Wang1*, Hong Yu5*, Yuanyuan Shao1*, Huijuan Jiang1*, Shan Gao1*, Lijuan Li1*, Rong Fu2* and Zonghong Shao1

1Department of Hematology, General Hospital of Tianjin Medical University, Tianjin, China
2Department of hematology, Tianjin Medical University General Hospital, Tianjin, China
3Department of Hematology, Xingtai People's Hospital, Xingtai, China
4Department of Hematology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
5Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China

BackgroudPrimary central nervous system lymphoma (PCNSL) represents approximately 2% of all primary central nervous system tumors and 4% to 6% of all extranodal lymphomas. The incidence of PCNSL has been increasing in recent years, and the median age at diagnosis was 65 years old. Most PCNSLs are diffuse large B-cell lymphoma (DLBCL; 90%-95%). PCNSL-DLBCL is a rare and highly aggressive lymphoma, due to its characteristics and special involved sites,previous treatment effect is disappointing with poor prognosis.

Aim: This study aims to evaluate the clinical efficacy and safety of Zanubrutinib combined with Lenalidomide, Temozolomide and Rituximab monoclonal antibody ±Methotrexate (RLZT±MTX) as first-line treatment for primary central nervous system lymphoma, especially in elderly patients who cannot tolerance to intensive chemotherapy.

Methods: The prospective, multicenter, open-label study planned to enroll 40 patients(Registration number:ChiCTR2000039485). Group A (RLZT+MTX) :eligible 20 young patients were ≤65 years, with normal kidney function. Patients in arm A were treated with regimen 1 and 2 alternately, each 3 courses, A total of 6 courses; Group B (RLZT) :eligible 20 elderly patients were >65 years or ≤65 years frail patients or patients with kidney dysfunction, regimen 2 was used for a total of 6 courses. Regimen 1: high-dose MTX (3.5g/m2) every 28 days; Regimen 2: RLZT (Rituximab 375mg/m2 IV D1, Lenalidomide 15mg/m2 D1-21, Zanubrutinib 160mg bid D1-21, Temozolomide 150mg/m2 Po D1-5) every 28 days. Note: 1. In group A, if patients who did not have a CR or PR after 6 cycles of the above regimen then the whole-brain radiotherapy (WBRT) was recommended; If patients achieved a CR or PR, auto-HSCT consolidation therapy was feasible; If the patient is not willing to transplant, enter single-agent oral Zanubrutinib to maintain until disease progression or intolerance.2. In group B, if patients who did not have a CR or PR after 6 cycles RLZT then the whole-brain radiotherapy (WBRT) was recommended, if patients achieved a CR or PR, maintain Zanubrutinib until diseaseprogression or intolerance.

Results: The data cut-off date was June 30, 2022, totally 24 patients enrolled in this clinical trial,both groups had 12 patients(Table 1). The ORR in the 24 PCNSL pts was 79.2%, with 9 (37.5%) complete responses (CR) and 10 (41.7%) partial responses (PR), in addition, 2 (8.3%) stable disease (SD) and 3 (12.5%) progressive disease (PD) were observed. The ORR was 66.7% (CR:16.7%, PR 50%) in the RLZT+MTX group and 91.7% (CR:58.3%, PR 33.3%) in the RLZT group. The median PFS and OS were not achieved in total patients,and the estimated 18-months OS and PFS were 95.8% and 78.2%, respectively. Similarly, The median PFS and OS were not achieved in both groups,estimated 18-months OS was 91.7% in the RLZT+MTX group and 100% in the RLZT group. The estimated 18-months PFS was 81.5% in the RLZT+MTX group and 80% in the RLZT group (Figure1).

Overall, 50%patients had experienced hematologic toxicity. Only 1 patient had grade ≥3 thrombocytopenia event and 1 patient had grade ≥3 leukopenia event. The overall incidence of non-hematologic toxicity was 50%, including gastrointestinal reactions, rash, liver and kidney damage, but only one patient had≥3 grade AE (rash). In addition, pneumonia was reported in 16.7% (4/24) of the patients, but no deaths were due to adverse events (Table 2).

Conclusions: This study showed that RLZT+MTX was an effective and safety first-line treatment for PCNSL patients. It is worth noting that in elderly patients who cannot tolerate high-dose chemoradiotherapy, RLZT shows a promising prospect.

Keywords:Primary central nervous system lymphoma, Zanubrutinib, first-line treatment

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH