2021 EHA Voice of China Professor Zhou Daobin's team new progress: R2-MTX regimen for the treatment of newly diagnosed PCNSL

Primary central nervous system lymphoma (PCNSL) has a rapid clinical course and a poor prognosis.
It is a rare subtype of extranodal non-Hodgkin's lymphoma
.

The treatment plan based on high-dose methotrexate (HD-MTX) has significantly improved the prognosis of patients, but there are still 10%-35% of patients whose treatment is ineffective
.

The team of Professor Daobin Zhou from Peking Union Medical College Hospital conducted a study to evaluate the safety, effectiveness and feasibility of the combined regimen of lenalidomide, rituximab and HD-MTX (R2-MTX) in the treatment of newly diagnosed PCNSL patients
.

The research was selected as the oral report of this year's EHA annual meeting.
The editor summarizes its main contents as follows for the reference of readers
.

Abstract Number: S223 Title: Phase IB/II Study: Combination therapy of lenalidomide, rituximab, and high-dose methotrexate (R2-MTX), followed by lenalidomide maintenance treatment for newly diagnosed primary central nervous system Systematic lymphoma research method This is a multi-center, prospective phase Ib/II study (NCT04120350)
.

Patients were enrolled in the group as follows: newly diagnosed PCNSL, age ≥18 years old, and normal terminal organ function
.

The Phase Ib study used a 3+3 dose escalation design
.

Lenalidomide 15mg (days 1-14) (level 1), 20mg (days 1-14) (level 2) and 25mg (days 1-14) (level 3) daily; rituximab The dose is 375mg/m2 (d0); the dose of methotrexate is 3.
5g/m2 (d1)
.

Every 21 days is a treatment cycle, and the R2-MTX regimen is treated for 6 cycles, followed by lenalidomide maintenance treatment (25 mg daily, 1-21 days, 28 days as a cycle), for a maximum of 2 years
.

In the phase I study, dose limiting toxicity (DLT) was evaluated during the first 2 treatment cycles to determine the recommended dose for phase II
.

Research results From August 2019 to December 2020, a total of 17 patients were included in the study: 10 patients participated in the Phase Ib study (lenalidomide dose: 3 patients 15mg, 4 patients 20mg, 3 patients 25mg), 7 patients participated Phase II study
.

No DLT was observed in the phase Ib study, and the recommended phase II dose of lenalidomide is 25 mg daily
.

The last follow-up time was January 31, 2021.
11 patients (64.
7%) were male, and the median age was 60 years (32-74 years)
.

According to the IELSG score (2-5 points), there are 13 cases of intermediate-risk and high-risk patients
.

Common ≥ grade 3 adverse events (AE) of induction therapy were neutropenia (41.
2%), infection (5.
9%), anemia (5.
9%), thrombocytopenia (5.
9%) and acute kidney injury (5.
9%) (One case of methotrexate overdose had all the above AEs); other AEs (grade 1-2, >10%) included elevated ALT (47.
1%), fatigue (29.
1%), nausea/vomiting (23.
5%) , Numbness (23.
5%), infection (11.
8%), kidney injury (11.
8%) and skin rash (11.
8%)
.

The curative effect can be evaluated in 16 patients, and the overall response rate (ORR) is 100%, of which 10 patients have complete remission and 6 patients have partial remission
.

The median follow-up time was 13.
2 months (1.
3-17.
3), 4 patients relapsed, 2 patients died of disease progression, and the median PFS was 13.
3 months
.

Research conclusions The R2-MTX regimen is a feasible and effective combination treatment regimen for newly diagnosed PCNSL patients, with high effective rate and well tolerated
.

This study (NCT 04120350) is still in progress, and more clinical data will continue to be updated
.

Reference source: Yan Zhang, et al.
PHASE IB/II STUDY OF LENALIDOMIDE, RITUXIMAB, HIGH-DOSE METHOREXATE (R2-MTX) REGIMEN, FOLLOWED BY LENALIDOMIDE MAINTAINANCE IN NEWLY DIAGNOSED PRIMARY CNS LYMPHOMA.
2021 EHA Annual Meeting.
Abstract S223.
"Read the original", we make progress together