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

On Sunday 2 December 2018, during the 60^th 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