2021 ICML indolent non-Hodgkin's lymphoma treatment options

The 17th International Conference on Malignant Lymphoma (ICML) was held in the near future.
At the conference, a number of indolent non-Hodgkin’s lymphoma related research progress, maintenance treatment plan for mucosa-associated lymphoid tissue (MALT) lymphoma, follicular lymphoma, and follicular lymphoma were announced.
The selection of tumor (FL) induction program was explored
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The editor now organizes the main content of the research as follows for the reference of readers
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Abstract 79: Efficacy and safety of rituximab maintenance therapy in patients with MALT lymphoma: Phase II IELSG38 study results 1 research background IELSG19 study results show that compared with other single-agent regimens, rituximab combined with benzene The first-line treatment of chlorambucil in MALT lymphoma can significantly improve event-free survival (EFS) and progression-free survival (PFS)
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The International Organization for Extranodal Lymphoma is now working with the Italian Lymphoma Foundation and the Lymphoma Research Association to explore maintenance therapy with rituximab among MALT lymphoma patients receiving rituximab combined with chlorambucil as first-line treatment The efficacy and safety
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2 Research methods The study included patients with new-onset or recurring MALT lymphoma after local treatment/antibiotic treatment without limitation to the external site, who received chlorambucil (6mg/m2/d, first 1-6, 9-10, 13-14, 17-18, 21-22 weeks orally) and rituximab (Intravenous injection of 375 mg/m2 on the first day of weeks 1, 2, 3, and 4; subcutaneous injection in weeks 9, 13, 17, and 21 1400mg) induction therapy
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Patients who achieved complete remission (CR), partial remission (PR), and stable disease (SD) after induction therapy received maintenance therapy with rituximab (1400 mg, once every two months) for 2 years
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3 Research results The study included 112 patients with a median age of 65 years (range: 32-86), of which 59 were male patients
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32% of patients had gastric MALT lymphoma, and 68% of patients had non-gastric MALT lymphoma
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56% of patients had stage III-IV disease
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Patients with low-risk, intermediate-risk, and high-risk MALT-IPI scores accounted for 29%, 40%, and 30%, respectively
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24 patients did not complete the study treatment, and 15 patients stopped treatment before the maintenance treatment started (4 due to drug-related adverse events [AE], 3 due to non-drug-related AE, 2 due to disease transformation, disease progression, second tumor , Protocol deviation, patient withdrawing from the study, investigator's decision to withdraw from the study, and withdrawing consent (1 case each)
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Nine patients were discontinued during maintenance treatment (3 due to drug-related AEs, 2 due to disease progression, 2 due to second tumors, 1 patient withdrew from the study, 1 patient protocol deviation)
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The most common hematological AEs ≥ Grade 3 were neutropenia (33%), lymphopenia (16%), and leukopenia (14%)
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Severe AEs occurred in 5 patients (1 case each of unexplained fever, sepsis, pneumonia, acute respiratory distress syndrome, and progressive multifocal leukoencephalopathy)
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87% of patients achieved CR
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At the end of maintenance therapy, the CR rate of the intention-to-treat population increased from 53% at the end of induction therapy to 65%
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At a median follow-up of 65 months (IQR: 58-69), the median EFS, PFS, and overall survival (OS) were not reached, and the 5-year EFS rate was 76% (95%CI: 67%-83%).
The 5-year PFS rate was 87% (95%CI: 79%-92%), and the 5-year OS rate was 93% (95%CI: 86%-96%)
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4 Research conclusions The IELSG38 study is the first study to evaluate the efficacy and safety of rituximab maintenance therapy in MALT lymphoma
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The study did not find new safety signals, and most patients achieved long-term disease control
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Although the study has a higher proportion of high-risk patients than the IELSG19 study (30% vs 17%), the results of the study show a higher 5-year PFS rate (87% vs 72%)
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Abstract 81: Nivolumab combined with rituximab in the first-line treatment of FL: Phase II 1st FLOR study results 1 Research background Standard immunochemotherapy regimens are more effective in the first-line treatment of FL, but this regimen is also accompanied by certain toxicity.
75% of patients may have AEs such as grade 3-5 infection and bone marrow suppression
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The first-line treatment of FL requires an equally effective and safer treatment plan
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The combination of PD-1 inhibitors and rituximab can increase the anti-tumor effect of T cells and enhance the antibody-dependent cytotoxicity of NK cells.
This combination program has shown a practical effect in relapsed FL
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The use of nivolumab before tumor treatment to "prepare" the immune system is reasonable and relevant evidence, but there is no research to confirm the safety of this regimen in the first-line treatment of FL
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2 Research methods The 1st FLOR study (NCT03245021) is an open-label, multi-center phase II study that included patients with stage III-IV stage 1-3a FL who needed first-line systemic treatment, ECOG score ≤2, and adequate organ function
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In the study, patients first received 4 cycles of nivolumab induction therapy (240 mg, 2 times a week), and patients who reached CR after induction therapy received 4 cycles of nivolumab monotherapy (240 mg, each 2 times a week), followed by 12 cycles of nivolumab maintenance therapy (480 mg, once every 4 weeks); and patients who did not reach CR after induction therapy received 4 cycles of rituximab monotherapy (Twice a week), followed by maintenance therapy of nivolumab combined with rituximab (Nivolumab 480mg, once every 4 weeks, for a total of 12 cycles; rituximab every 12 weeks 1 time, 8 cycles in total)
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The primary endpoint of the study was the incidence of AE ≥ grade 3, and the secondary endpoints were the overall response rate (ORR), overall adverse reactions, PFS, and OS
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3 Research results The study included 39 patients from September 2017 to March 2020, with a median age of 54 years (range: 28-79)
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67% of patients had stage IV disease, 23% of patients had B symptoms, 23% of patients had large masses (≥7cm), and 74% of patients had a medium-high-risk FLIPI score
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After the induction treatment, 16 patients (41%) had AEs ≥ Grade 3
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The non-immune AEs in the study were mainly grade 1-2, and the most common non-immune AEs were infection (67%) and fatigue (64%)
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Grade 3-4 immune-related AEs are less, including pancreatitis + hepatitis (n=1), pancreatitis (n=1), skin rash (n=1), elevated transaminases (n=2), hypocortisolism ( n=1), hyperglycemia (n=3), asymptomatic elevation of lipase/amylase (n=3)
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At a median follow-up of 17.
5 months (range: 7-39), the ORR of the program was 92% (36/39), the CR rate was 54% (21/39), and the intermediate CR time was 5 months (range 2 -25)
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Nine patients (23%) discontinued treatment (7 disease progression [1 patient died of FL disease conversion], 2 patients developed systemic symptoms [1 PR, 1 SD])
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Among 25 patients with evaluable PFS and OS, the 12-month PFS rate was 72% (95%CI: 51%-88%), and the 12-month OS rate was 96% (95%CI: 80%-100%) )
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4Research conclusions Firstly, the use of nivolumab to stimulate the immune system, followed by the use of nivolumab combined with rituximab in the first-line treatment of FL showed better safety and higher ORR and CR rates
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This program provides a new treatment option in addition to immunochemotherapy for the first-line treatment of FL
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References: 1.
MC Pirosa, et al.
2021 ICML.
Supplement Abstract No.
79.
2.
EA Hawkes, et al.
2021 ICML.
Supplement Abstract No.
81.
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