Long-term follow-up and correlative analysis of two phase II trials of rituximab and lenalidomide followed by continuous lenalidomide in untreated and relapsed/ refractory indolent lymphoma

Joseph Tuscano, Christina Poh, Paul Kaesberg, Guilluame Luxardi, Alexander Merleev, Alina Marusina, Ann Brunson, Aaron Rosenberg, Brian Jonas, Emanual Maverakis

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Rituximab and lenalidomide are effective for previously untreated and relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). However, long-term survival and predictive biomarkers are not well described. Patients and Methods: We conducted two phase II open-label trials involving 60 patients with previously untreated and R/R advanced-stage iNHL. Patients received lenalidomide and rituximab induction followed by continuous lenalidomide until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Correlative studies included plasma cytokine monitoring, flow cytometry of peripheral blood mononuclear cells (PBMC; days 0, 15, 30, and 60), and RNA sequencing (RNA-seq) of pretreatment tumor biopsies. Results: At a median follow-up of 63 months for previously untreated and 100 months for R/R, ORR was 82% for both. The 11 R/R patients who achieved complete remission remained in continuous remission for 16 to 141 months, thereafter. Median overall survival (OS) was not reached in the previously untreated and was 140 months (95% confidence interval, 53.4-140) in the R/R group. A mixed-effects linear regression model identified significant associations between Granzyme B+ (GranB+) CD8+ T cells and long-term complete response (LTCR; P = 5.3e-4). Furthermore, prior to start of therapy, treatment response could be predicted by B-cell and GranB+ CD8+ T-cell levels (% total lymphocytes). Conclusions: Rituximab plus lenalidomide followed by continuous lenalidomide is effective with manageable toxicity in patients with previously untreated and R/R iNHL. This regimen produces durable remissions, even in heavily pretreated patients, with some lasting greater than 10 years. GranB+ CD8+ T cells, B cells, and plasma IFNγ allowed prediction of LTCR but need validation in larger trials.

Original languageEnglish (US)
Pages (from-to)4726-4736
Number of pages11
JournalClinical Cancer Research
Volume27
Issue number17
DOIs
StatePublished - Sep 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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