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ASH 2018 | Rituximab, ibrutinib, and lenalidomide combination promising for previously-untreated MZL and FL patients

Jan 10, 2019
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On Sunday 2 December 2018, during the 60th Annual Meeting of the American Society of Hematology (ASH), San Diego, CA, Loretta Nastoupil from the University of Texas MD Anderson Cancer Center, Houston, TX, USA, presented Abstract #447 during Oral Session #623.

During this talk, the results of an open-label, phase II trial were presented that investigated the efficacy and safety of ibrutinib in combination with rituximab and lenalidomide in previously-untreated patients with follicular lymphoma (FL) or marginal zone lymphoma (MZL). The primary endpoint of the study was progression-free survival (PFS) at two years follow-up. Secondary endpoints included, safety, overall response rate (ORR), complete response (CR), and overall survival (OS). The study also included an exploratory objective of identifying predictive biomarkers.

Study design

  • Trial duration: April 2016 and February 2018 (single center study)
  • N = 48 adult, previously-untreated patients with MZL (n = 10) or FL (n = 38) with the following eligibility criteria:
    • In need of systemic therapy
    • Disease stage: II, III or IV
    • Easter Cooperative Oncology Group (ECOG) performance status ≤ 2
    • No evidence of CNS disease
  • Dosing (28-day cycles):
    • Rituximab: 375 mg/m2 on Day 1, 8, 15, 22 of cycle one and then on Day 1 of cycles 2−12
    • Lenalidomide: 15 mg on Days 1−21 od cycle one and then 20 mg on Days 1−21 of cycles 2−12
    • Ibrutinib: 560 mg on Days 1−28 of cycles 1−12
  • Baseline characteristics:
    • Median age (range): 59 (37−81) years
    • Sex: 67% males
    • Lymphoma subtype:
      • FL: 79% (n = 38) [Grade 1−2: 92%; Grade 3a: 5%]
      • MZL: 21% (n = 10) [NMZL: 40%; SMZL: 30%; MALT: 30%]
    • High tumor burden: 61% of patients
    • Disease stage II/III/IV: 6%/25%/69%
    • FL International Prognostic Index (FLIPI) score:
      • 0−1 (low risk): 15%
      • 2 (intermediate risk): 46%
      • ≥ 3 (high risk): 39%

Results

  • PFS at a median follow-up of 24 months (range, 6−29): not reached
  • Two-year PFS estimation: 78% (95% CI, 66−94%)
  • Response rates (Lugano criteria):
    • ORR for entire study population (n = 48): 94%
    • ORR for MZL cohort (n = 10): 90%
    • ORR for FL cohort (n = 38): 95%
    • CR rate for entire study population (n = 48): 81%
  • Achieving CR was independent of lymphoma subtype, sex, FLIPI score or tumor burden
  • No deaths have yet been recorded

Safety

  • Seven patients discontinued treatment due to the following treatment-emergent adverse events (TEAEs):
    • Recurrent rash: n = 3 (Grade 3)
    • Ventricular arrhythmia: n = 1 (Grade 4)
    • Pneumonitis: n = 2 (Grade 2)
    • Pneumonia: n = 1 (Grade 3)
  • The most common Grade 3 TEAEs observed were:
    • Rash
    • Diarrhea
    • Neutropenia
    • Fatigue
    • Cytopenia
    • Bleeding
    • Pneumonitis
    • Dyspnea
    • Pneumonia
  • Neutropenia was the only Grade 4 TEAE observed

Conclusions

  • Ibrutinib, rituximab, and lenalidomide combination shows promising efficacy outcomes in previously-untreated FL and MZL patients; and particularly for MZL patients
  • Toxicity profile is manageable
  • Lenalidomide dose modification during cycle one did not significantly impact the incidence of Grade 3 rash
  • Still ongoing analysis, conclusions cannot yet be drawn due to the small sample size
  1. Nastoupil L.J. et al. Safety and Efficacy of Ibrutinib in Combination with Rituximab and Lenalidomide in Previously Untreated Subjects with Follicular and Marginal Zone Lymphoma: An Open Label, Phase II Study. Oral Abstract #447: ASH 60th Annual Meeting and Exposition, December 2018, San Diego, CA.
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