The Lynx Group

The iR² Regimen (Ibrutinib, Lenalidomide, and Rituximab) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Conference Correspondent

Ibrutinib, a drug that blocks Bruton’s tyrosine kinase (BTK), is approved to treat various blood cancers, including chronic lymphocytic leukemia (CLL). Using animal data, researchers have learned that ibrutinib combined with lenalidomide may have synergistic activity.1 Another drug, rituximab, is also active when combined with ibrutinib in people with various types of non-Hodgkin lymphoma.2

The PCYC-1123 trial is evaluating a new 3-drug combination for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), an aggressive type of non-Hodgkin lymphoma (NHL). This combination includes ibrutinib, lenalidomide, and rituximab and is called iR2.

Adult patients with relapsed or refractory DLBCL who were not eligible for stem-cell transplant (SCT) received lenalidomide on days 1 to 21 of each 28-day cycle combined with ibrutinib orally once daily, and rituximab given via intravenous infusion on day 1 of each of 6 28-day cycles. Treatment continued until the disease progressed or until toxicity became unacceptable.

A total of 89 patients with DLBCL were enrolled and treated in the phase 2 portion of this trial. Their median age was 64 years, and most (58%) were male. At study entry, 53% of patients were refractory to their last therapy, while 47% had relapsed. The median number of prior therapies for DLBCL was 2.

To date, 85 patients with relapsed or refractory DLBCL who received iR2 have been assessed for response. Among these patients, 47% achieved a response, either complete remission (28%) or partial remission (19%). Another 16% had stable disease. Among the 40 patients who responded, responses lasted 18 months (median), ranging from less than 1 to 22 months. At 18 months, 31% of patients were free of disease progression. Among all patients, median progression-free survival (PFS) was 5 months.

At 18 months, 44% of patients with relapsed or refractory DLBCL who received iR2 were still alive. Median overall survival (OS) was 14 months. Among the 40 responders to iR2, median PFS was 21 months and median OS had not yet been reached. Fourteen of the responding patients (16%) remained in complete response for more than 1 year.

Side effects that occurred in more than 30% of patients were diarrhea (53%), fatigue (42%), low white blood-cell count (40%), cough (34%), anemia (33%), swelling (33%), and rash (31%). The most common serious side effects were low white blood-cell count (36%) and rash (18%). Twelve patients died; 7 due to worsening DLBCL, and 5 for reasons unrelated to their cancer, including pneumonia, sepsis, and cardiac arrest.

Researchers concluded that the iR2 combination is effective with a response rate of 47%, including durable complete responses lasting for up to 22 months. The safety of this 3-drug combination was manageable. The value of the iR2 regimen in DLBLC will continue to be studied in clinical trials.

  1. Yang Y, Shaffer AL, Emre NC, et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell. 2012;21(6):723-737.
  2. Wang ML, Lee H, Chuang H, et al. Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial. Lancet Oncol. 2016;17(1):48-56.

Abstract 761. ASH 2019.

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