Conference Correspondent

Smart Start: Final Results of Rituximab, Lenalidomide, and Ibrutinib Lead-In Therapy for Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma

Conference Correspondent - ASCO 2019 - Chronic Lymphocytic Leukemia

Patients diagnosed with the non-germinal center B-cell (non-GCB) subtype of diffuse large B-cell lymphoma (DLBCL) have inferior outcomes with standard immunochemotherapy. The Bruton’s tyrosine kinase inhibitor ibrutinib and the immunomodulator lenalidomide both have shown promising clinical activity in non-GCB DLBCL as single agents, and the combination has demonstrated synergistic action in preclinical models. In a prior study, the combination of rituximab, lenalidomide, and ibrutinib (RLI) in relapsed non-GCB DLBCL showed an overall response rate (ORR) of 55%.1 At the ASCO 2019 Annual Meeting, researchers reported the final results of rituximab, lenalidomide, and ibrutinib combination treatment given prior to chemotherapy in newly diagnosed non-GCB DLBCL patients.

In this single-arm, open-label, phase 2 study, adult patients with newly diagnosed non-GCB DLBCL who had adequate organ function and performance status were eligible. The primary objectives were to determine the ORR at the end of 2 cycles of RLI alone, and to determine the complete response rate (CRR) after 2 cycles of RLI followed by 6 cycles of chemotherapy plus RLI. All patients were treated with a 375-mg/m2 dose of rituximab administered intravenously on day 1, oral ibrutinib 560 mg daily, and 25 mg of oral lenalidomide given on days 1 through 10 of 21-day cycles for 2 cycles, followed by 6 additional cycles of rituximab, lenalidomide, and ibrutinib plus chemotherapy.

A total of 60 patients were enrolled, with 58 patients evaluable for disease response. The median age was 64 years, and 50% were male. A majority of the evaluable patients had high-risk disease characteristics, 65% had advanced-stage disease, and 77% had a Ki-67 of ≥80%. In terms of safety, the most commonly reported adverse events included nausea, peripheral sensory neuropathy, and diarrhea. One patient experienced fatal central nervous system aspergillosis; this was attributed to high-dose corticosteroids plus rituximab, lenalidomide, and ibrutinib, leading researchers to prohibit concomitant use of corticosteroids during the rituximab, lenalidomide, and ibrutinib-only cycles.

The ORR for 2 cycles of rituximab, lenalidomide, and ibrutinib was 86%, and the CRR was 36%. Median time to progression and median overall survival were not reached. One patient refused to proceed with the preplanned chemotherapy after achieving a CR with 2 cycles of rituximab, lenalidomide, and ibrutinib, and remained relapse-free at the data cutoff.

In sum, the Smart Start trial demonstrated that the combination of rituximab 375 mg/m2, ibrutinib 560 mg, and lenalidomide 25 mg is effective in patients with newly diagnosed non-GCB DLBCL. Additional studies are evaluating an adjusted regimen with more cycles of rituximab, lenalidomide, and ibrutinib with less chemotherapy consolidation.

Abstract 7508; Westin J, et al.


Reference

  1. Ramchandren R, Johnson P, Ghosh N, et al. The iR2 regimen (ibrutinib, lenalidomide, and rituximab) is active with a manageable safety profile in patients with relapsed/refractory non-germinal center-like diffuse large B-cell lymphoma. Blood. 2018;132:402.
Related Items
Effect of Fixed-Duration Venetoclax plus Obinutuzumab on Progression-Free Survival and Minimal Residual Disease Status in Treatment-Naïve Patients with CLL and Comorbidities
Conference Correspondent published on June 4, 2019 in ASCO 2019 - Chronic Lymphocytic Leukemia
Comparison of 3 Rituximab-Containing Regimens as Primary Therapy in Patients with WM
Conference Correspondent published on June 4, 2019 in ASCO 2019 - Chronic Lymphocytic Leukemia
Three-Year Follow-Up of Acalabrutinib and Obinutuzumab in Treatment-Naïve and Relapsed/Refractory CLL
Conference Correspondent published on June 4, 2019 in ASCO 2019 - Chronic Lymphocytic Leukemia
Patient-Reported Outcomes with Ibrutinib-Rituximab in WM: Results from iNNOVATE
Conference Correspondent published on June 4, 2019 in ASCO 2019 - Chronic Lymphocytic Leukemia
Evaluation of MRD with Lisocabtagene Maraleucel, a CD19-Directed CAR T Therapy, in Patients with Relapsed/Refractory CLL/SLL
Conference Correspondent published on June 4, 2019 in ASCO 2019 - Chronic Lymphocytic Leukemia
Last modified: June 6, 2019
  •  Association for Value-Based Cancer Care
  • Oncology Practice Management
  • Value-Based Cancer Care
  • Value-Based Care in Rheumatology
  • Rheumatology Practice Management
  • Urology Practice Management
  • Lynx CME