The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Hematology Advisor‘s conference coverage.

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.


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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.

Read more of Hematology Advisor’s coverage of the ASH 2020 meeting by visiting the conference page.

References

  1. 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.
  2. 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