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Acalabrutinib with lenalidomide and rituximab for R/R aggressive B-cell non-Hodgkin lymphoma

May 17, 2024
Learning objective: After reading this article, learners will be able to cite a new development in the treatment of relapsed/refractory aggressive B-cell non-Hodgkin lymphoma.

Rituximab plus chemoimmunotherapy has improved outcomes for patients with CD20+ aggressive B-cell non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL); however, a significant portion of patients relapse. While chimeric antigen receptor T-cell therapy has demonstrated efficacy in patients with relapsed/refractory (R/R) DLBCL, alternative strategies are being explored due to the potential financial burden of this treatment.1 The combination of Bruton's tyrosine kinase inhibitors with lenalidomide and rituximab could be an effective regimen for patients with R/R aggressive B-cell NHL.1

Park et al.1 recently published results from a phase II trial (NCT04094142) assessing the safety and efficacy of acalabrutinib, a Bruton's tyrosine kinase inhibitor, in combination with lenalidomide and rituximab (R2A regimen) in patients with R/R B-cell NHL in Nature Communications. Below, we summarize the key findings.

Study design and patient population1

  • This was an open-label, single-arm phase II trial.
  • Patients received 375 mg/m2 rituximab intravenously on Day 1, 20 mg lenalidomide orally once daily on Days 1–21, and 100 mg acalabrutinib orally twice daily on Days 1–28, repeated every 4 weeks for up to 6 cycles.
    • Patients with a response could receive acalabrutinib monotherapy as maintenance therapy for up to one year.
  • The primary endpoint was the objective response rate (ORR).

Key findings1

Patient characteristics

  • In total, 66 patients received treatment, most of whom had DLBCL (Table 1).
  • The median age was 67.5 years (range, 20–87).

Table 1. Pathological diagnosis of patients treated with R2A regimen*

Pathological diagnosis, %

Patients (n = 66)













DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; GCB, germinal center B-cell type; non-GCB, non-germinal center B-cell type; NOS, not otherwise specified; PCNSL, primary central nervous system lymphoma; PMBCL, primary mediastinal B-cell lymphoma; R2A, acalabrutinib with lenalidomide and rituximab.
*Adapted from Park, et al.1


  • The ORR and complete remission rate were 54.5% and 31.8%, respectively (Figure 1).
    • The ORR and complete remission rate were not significantly different between patients with non-germinal center B-cell type DLBCL and germinal center B-cell type DLBCL (p = 0.179 and p = 0.310, respectively; Figure 1).
  • The median duration of response was 12.9 months and median progression-free survival was 4.4 months.
  • The 1-year progression-free survival and overall survival rates were 33.1% and 67.5%, respectively.
  • In total, seven patients had MYD88 mutations, and the median progression-free survival among these patients was 4.5 months.

Figure 1. Objective response rate and complete remission rate in patients receiving the R2A regimen*

DLBCL, diffuse large B-cell lymphoma; GCB, germinal center B-cell; NOS, not otherwise specified; R2A, acalabrutinib with lenalidomide and rituximab.
*Data from Park et al.1 


  • In total, 39 patients experienced adverse events, most commonly neutropenia (n = 21), skin rash (n = 17), thrombocytopenia (n = 6), and pruritus (n = 6).
Key learnings
  • The R2A regimen was well tolerated and showed high efficacy in patients with R/R aggressive B-cell NHL.
  • In addition, exploratory analysis showed that patients with MYD88 mutations responded well to the R2A regimen.

  1. Park C, Lee HS, Kang KW, et al. Combination of acalabrutinib with lenalidomide and rituximab in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma: a single-arm phase II trial. Nat Commun. 30;15(1):2776. DOI:10.1038/s41467-024-47198-4

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