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The combination of lenalidomide (Revlimid) plus rituximab (Rituxan) continues to demonstrate long-term efficacy when used as initial induction therapy in patients with mantle cell lymphoma (MCL), according to multicenter, phased, long-term data. Durable response with controlled safety 2 study (NCT01472562).1
According to the study’s 9-year follow-up results, lenalidomide plus rituximab as induction and maintenance until progression, with the option to discontinue after 3 years, showed a progression-free survival (PFS) of 51% (95% CI, 31.5-68.0) and overall survival (OS) rates were 66% (95% CI, 47.3-79.2) respectively.
For safety reasons, hematologic adverse events (AEs) observed during maintenance were asymptomatic grade 3 or 4 cytopenias, including neutropenia (42%), thrombocytopenia (5%), and anemia (3%) . Most grade 1 to 2 infections, including upper respiratory tract infections (50%), urinary tract infections (21%), sinusitis (16%), cellulitis (16%), and pneumonia (13%), were treated on an outpatient basis. Five percent of these infections require hospitalization.
Currently, chemoimmunotherapy is the standard treatment for initial treatment of MCL. However, new data suggest that chemotherapy-free approaches may have potential in this patient population. This idea was further investigated in phase 2 trials.
The study is open to patients with measurable, histologically confirmed, untreated MCL with a low- to intermediate-risk MCL International Prognostic Index (MIPI) score or a high-risk MIPI score and a contraindication to chemotherapy, ECOG Performance status score ≤ 2, creatinine clearance ≥ 30mL/min.2
During the induction phase, patients received lenalidomide 20 mg daily for the first 21 days of a 28-day cycle for 12 cycles, with the dose increased to 25 mg daily after the first cycle as tolerated. During the maintenance phase, the dose of lenalidomide was reduced to 15 mg daily. Patients with creatinine clearance between 30 and 60 mL/min had lenalidomide dose adjusted to 10 mg daily for induction and 5 mg daily for maintenance. In addition, patients were given 375 mg/m2 of rituximab weekly for 4 weeks in cycle 1 and then every other cycle, including the maintenance period.
Patients continued treatment until disease progression, unacceptable AEs, or voluntary withdrawal from the study. Furthermore, treatment can be discontinued after 3 years if the patient is in clinical remission according to computed tomography.
Between July 2011 and April 20124, 38 patients with untreated MCL requiring treatment were enrolled at 4 centers. The median age of patients was 65 years (range: 42-86 years). Patients mostly had advanced disease, with MIPI scores evenly distributed between low, intermediate, and high risk. A total of 87% of patients had evaluable Ki67 markers, 21% had >30% Ki67, and none had pleomorphic or blastic histology.1
Of 36 patients evaluable for response, 33 completed the induction phase of treatment and initiated maintenance therapy with lenalidomide and rituximab. Disease progression occurred in 15 patients, including 3 patients during induction therapy for primary refractory disease and 12 patients during maintenance therapy after initial remission. Six patients who progressed during the maintenance period achieved initial complete response (CR), with PFS of 18, 38, 39, 49, 72 and 85 months, respectively. The other six patients achieved initial partial response and achieved PFS at 14, 25 and 28 months. Progression occurred at, 43, 44, and 92 months, respectively.
Previous trial data showed an overall response rate of 92% among evaluable patients in the study, with 64% achieving a complete response (CR). At a median follow-up of 103 months, 17 of 36 evaluable patients (47%) remained in remission.
During the maintenance period, 12 patients with CR discontinued study treatment, and 10 patients maintained durable remission. Although MIPI score was not associated with either response or PFS, high-risk MIPI score was associated with worse OS (ask =.03). Furthermore, Ki67 >30% did not have an impact on PFS or OS, which is consistent with previous data.
More patients developed grade 1 and 2 neuropathy during maintenance therapy (29%) compared with induction therapy (8%), and 21% developed secondary malignancies, including invasive malignancies (5%). Additionally, during the COVID-19 pandemic, 2 patients permanently discontinued treatment due to immunosuppression issues.
“The (lenalidomide and rituximab) study is the first chemotherapy-free first-line treatment for MCL, and our report provides long-term data on the use of a chemotherapy-free approach to treat MCL. The first-line drugs (lenalidomide and rituximab) The efficacy of rituximab), demonstrated by high response rates and durable remissions as well as long-term safety and convenience of an outpatient treatment regimen, support the broad applicability of this regimen as a new approach to previously untreated MCL,” the study authors concluded.
refer to:
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Yamshon S, Chen GZ, Gribbin C, et al. Nine-year follow-up of lenalidomide plus rituximab as initial treatment for mantle cell lymphoma. blood advanced. 2023;7(21):6579-6588. doi:10.1182/bloodadvances.2023010606
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Lenalidomide plus rituximab is used to treat untreated mantle cell lymphoma. clinicaltrials.gov. Updated on September 7, 2023. Accessed November 16, 2023. https://tinyurl.com/38a8s8kx