The combination of lenalidomide and rituximab as first-line treatment for mantle cell lymphoma (MCL) in both older and younger patients yielded high rates of complete responses (CRs) with durable remissions, extending beyond 7 years in some cases, according to updated efficacy and safety data of a phase 2 study presented by Samuel Yamshon, MD, of Weill-Cornell Medicine in New York, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
“A chemotherapy-free approach using biologic agents could offer similarly effective control of disease, while offering a different toxicity profile, making it a viable approach for patients for whom cytotoxic chemotherapy might not otherwise be an option,” said Dr Yamshon.
The 7-year follow-up analysis comes after a prior 5-year report on this multicenter phase 2 study of lenalidomide plus rituximab in MCL (ClinicalTrials.gov Identifier: NCT01472562), which demonstrated high efficacy (overall response rate [ORR], 92%; CR, 64%) and durable responses (5-year progression free survival [PFS] and overall survival [OS], 64% and 77%, respectively).1,2
Patients received both lenalidomide and rituximab during induction and maintenance (12 cycles of lenalidomide induction at 20 mg/d, days 1-21 per 28-day cycle followed by maintenance, 15 mg, and rituximab weekly during cycle 1, then 1 dose every other cycle) until disease progression or patients stopped therapy (optional after 3 years). The primary objective was ORR, and secondary objectives included PFS, OS, and safety.
Between July 2011 and April 2014, a total of 38 untreated patients with tumor mass 1.5 cm or larger were enrolled in the study. The majority of patients were men (71%), and the median age was 65 years (42-86). Mantle cell lymphoma international prognostic index (MIPI) scores were approximately equal among low- (34%), intermediate- (34%), and high-risk (32%) groups.
Among evaluable patients (n=36), the ORR was 92% (64% CR and 28% PR). In total, 19 patients (53%) are still in remission, including 12 patients (33%) who have now been in remission for at least 7 years. Of the patients in remission, 10 (27%) remain on treatment: 1 patient taking lenalidomide, 2 patients taking lenalidomide/rituximab, and 7 patients taking rituximab. Due to side effects or patient preference, 9 patients opted to stop therapy after 3 or more years.
Of the 14 patients with disease progression, 3 patients had primary refractory disease, while 11 patients relapsed during the maintenance phase (8/11 died). Prior to relapse, 5 of these patients had achieved CR with PFS ranging from 18 to 72 months, while 6 patients had achieved PR with PFS ranging from 14 to 92 month. Additionally, 3 patients died due to unrelated comorbidities.
Median PFS and OS have not been reached. The estimated 7-year PFS was 60.3% (95% CI, 41.1-75.0), and the estimated 7-year OS rate was 73.2% (95% CI, 55.9-84.6). Patients with low-/intermediate-risk MIPI score (≤6.2) had increased 7-year OS relative to those with a high-risk MIPI score (80.6% vs 57.1%; log-rank P =.04).
During maintenance, grade 3 to 4 hematologic adverse events (AE), included neutropenia (42%), thrombocytopenia (5%), anemia (3%) and febrile neutropenia (5%). Grade 3 to 4 infections included, upper respiratory infection (3%), urinary tract infection (5%), sinusitis (3%), cellulitis (3%), and pneumonia (5%).
Nonhematologic AEs during maintenance (any; grade 3-4) included fatigue (55%; 3%), hyperglycemia (58%; 3%), elevated alanine aminotransferase (29%; 5%) and aspartate aminotransferase (37%; 8%), and hypogammaglobulinemia (5%; 5%). Secondary malignancy developed in 8 patients during both induction and/or maintenance (10 cutaneous, 1 pancreatic, and 1 Merkel cell).
“Overall, these long term data strongly justify further study of the lenalidomide and rituximab combination as initial therapy for mantle cell lymphoma,” concluded Dr Yamshon.
Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
- Yamshon S, Martin P, Shah B, et al. Initial treatment with lenalidomide plus rituximab for mantle cell lymphoma (MCL): 7-year analysis from a multi-center phase II study. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstract 704.
- Ruan J, Martin P, Shah B, et al. Lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma. N Engl J Med. 2015;373(19):1835-1844. doi:10.1056/NEJMoa1505237
This article originally appeared on Hematology Advisor