According to long-term data from a multicenter, phase I study, when given as initial induction therapy to patients with mantle cell lymphoma (MCL), the combination of lenalidomide (Revlimid) plus rituximab (Rituxan) provides manageable safety as well as long-term survival. And continues to show lasting response. Study 2 (NCT01472562).1
According to the 9-year follow-up results of the study, lenalidomide plus rituximab as induction and maintenance until progression, showed a progression-free survival (PFS) rate of 51% (95% CI, 31.5-) with elective discontinuation after 3 years. Went. 68.0) and overall survival (OS) rates would be 66% (95% CI, 47.3-79.2), respectively.
For safety, the most common 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 infections (50%), urinary tract infections (21%), sinusitis (16%), cellulitis (16%), and pneumonia (13%) were managed in the outpatient setting. Was. Five percent of these infections required hospitalization.
Currently, chemoimmunotherapy is the current standard of care for the initial treatment of MCL. However, new data suggests that a chemotherapy-free approach may have potential in this patient population. This idea was further studied in a phase 2 trial.
Enrollment into the study was open to patients with measurable, histologically confirmed, untreated MCL who had a low- to intermediate-risk MCL International Prognostic Index (MIPI) score or a high-risk MIPI score with contraindications to chemotherapy, An ECOG performance status score ≤ 2, and creatinine clearance ≥ 30 mL/min.2
During the induction phase, patients were treated with 20 mg lenalidomide 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. For the maintenance phase, the dose of lenalidomide was reduced to 15 mg daily. In patients with creatinine clearance between 30 and 60 mL/min the dose of lenalidomide was adjusted to 10 mg daily for induction and 5 mg daily for maintenance. Additionally, rituximab was administered to patients at a dose of 375 mg/m2 weekly during 4 weeks of cycle 1, then once every other cycle during maintenance.
Patients continued to receive treatment until disease progression, development of unacceptable AEs, or voluntary withdrawal from the study. Furthermore, if patients were in clinical remission based on computed tomography, they were able to discontinue treatment after 3 years.
Between July 2011 and April 20124, 38 patients with untreated MCL requiring treatment were enrolled at 4 centers. The mean age of the patients was 65 years (range, 42–86 years). Patients mostly had advanced stage disease, and MIPI scores were evenly distributed among low, intermediate, and high risk. A total of 87% of patients had evaluable Ki67 markers, 21% had Ki67 >30%, and none had pleomorphic or blastoid histology.1
Of the 36 patients evaluated for response, 33 completed the induction phase of therapy and began maintenance therapy with lenalidomide and rituximab. Disease progression was observed in fifteen patients, including 3 during induction therapy with primary refractory disease and 12 during maintenance after initial response. Six patients who progressed during maintenance had early complete responses (CR) with PFS of 18, 38, 39, 49, 72, and 85 months, respectively, and the other 6 patients had early partial responses (CR) with progression of 14, 25, 28 months, respectively. There were reactions. , 43, 44, and 92 months respectively.
Previous data from the trial showed that the overall response rate among evaluable patients included in the study was 92%, and 64% achieved complete response (CR). With a median follow-up of 103 months, 17 (47%) of 36 evaluable patients are still in remission.
During maintenance, 12 patients in CR discontinued study treatment and durable remission was maintained in 10 patients. Although MIPI scores were not associated with any response or PFS, higher risk MIPI scores were associated with less favorable OS (Why =.03). Furthermore, Ki67 >30% had no impact on PFS or OS, which was consistent with prior data.
More patients developed grade 1 and 2 neuropathies during maintenance therapy (29%) versus induction therapy (8%), and 21% of patients developed secondary malignancies, including invasive malignancies (5%). Additionally, 2 patients permanently discontinued treatment due to immunosuppression concerns during the COVID-19 pandemic.
“The (lenalidomide and rituximab) study is the first chemotherapy-free frontline treatment for MCL, and our report provides long-term data using a chemotherapy-free approach in MCL. The efficacy of first-line (lenalidomide and rituximab), as evidenced by high response rates and long-term safety with durable remissions, as well as the convenience of an outpatient treatment regimen, warrants broad-based consideration of this regimen as a novel approach. Supports usability. Previously untreated MCL,” the study authors concluded.
Yamshon S, Chen GZ, Gribbin C, et al. Nine-year follow-up of lenalidomide plus rituximab as initial treatment of mantle cell lymphoma. blood advice, 2023;7(21):6579-6588. doi:10.1182/bloodadvance.2023010606
Lenalidomide plus Rituxan for untreated mantle cell lymphoma. ClinicalTrials.gov. Updated on September 7, 2023. Accessed November 16, 2023. https://tinyurl.com/38a8s8kx