Long-term follow-up of 90Y ibritumomab tiuxetan consolidation in MCL patients

Immunochemotherapy followed by consolidation with autologous stem cell transplantation (ASCT) and/or rituximab maintenance is the current standard of care for patients with mantle cell lymphoma (MCL). However, this approach is not a feasible option for some patients, such as the elderly or unfit patients with comorbidities.

On 9 April , Wojciech Jurczak from Jagiellonian University Medical College, Krakow, PL, and colleagues, published in Leukemia & Lymphoma an 8-year follow-up of a phase II trial on behalf of the Polish Lymphoma Research Group.

This multicenter, prospective phase II study investigated whether radioimmunotherapy consolidation with ⁹⁰Y ibritumomab tiuxetan (RIT) is an efficient treatment for patients with MCL, who are ineligible to receive high-dose chemotherapy. The primary endpoints of the study were complete response (CR) rates after consolidation with the ⁹⁰Y-labeled anti-CD20 monoclonal antibody, and the feasibility of the regimen. Secondary endpoints included progression-free survival (PFS), and overall survival (OS).

Study design & baseline characteristics

• N = 46 patients with advanced MCL chemosensitive to first or second line chemotherapy, and not eligible for ASCT

Total number of patients	N = 46
Median patient age	60 (30−78) years
Male gender	70% (n = 32)
Advanced disease clinical stage (IV)	85% (n = 39)
Extranodal disease	87% (n = 40)
Bone marrow involvement	41% (n = 19)
B symptoms	70% (n = 32)
Elevated lactate dehydrogenase (LDH)	71% (n = 33)
MCL International Prognostic Index (MIPI) Low risk Intermediate risk High risk	5.8 (range, 4−7) 39% (n = 18) 32.6% (n = 15) 28.4% (n = 13)

• Treatment plan:
  • Induction chemotherapy regimens:
    • Cyclophosphamide, vincristine, and prednisone (CVP): C, 750 mg/m²; V, 1.4 mg/m² (maximum 2 mg); P, 60−100 mg on Days 1−5
    • Cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP): C, 750 mg/m²; H, 50 mg/m²; O, 1.4 mg/m² (maximum 2 mg); P, 60–100mg on Days 1–5
    • Fludarabine and cyclophosphamide (FC): F, 25 mg/m²; C, 250 mg/m² on Days 1−3
    • FC plus mithoxanthrone (FCM): F, 25 mg/m²; C, 250 mg/m² on Days 1−3 and M, 12.5 mg/m² on Day 1
    • Rituximab (R; 375 mg/m²) was not regarded a standard of care at the time so it was given depending on availability on Day 1 of every cycle in 58.5% of patients. No patient was given R maintenance
  • RIT: Patients responding to induction therapy were consolidated with RIT 3−5 weeks after the last chemotherapy cycle
    • RIT: Two doses of 250 mg/m² of R administered seven days and 24 hours prior to the intravenous injection of the ⁹⁰Y-labeled ibritumomab tiuxetan at a dose of 0.4 mCi/kg for patients with normal platelet count and 0.3 mCi/kg for those with platelet count between 100.,000 and 150,000 cells/mm³. Maximum dose was 32.0 mCi
  • Treatment assessments were performed at baseline, after the third chemotherapy cycle, before RIT and six weeks after RIT completion
• Median observation (range): 4.6 (0.4−12) years

Key findings

• Patients receiving induction chemotherapy as first-line (n = 34):
  • FCM/FC ± R: n = 20 patients
  • CHOP/CVP ± R: n = 14 patients
• Response rates from both induction treatments:
  • CR: 41% (n = 14)
  • Partial response (PR): 59% (n = 20)
• In this population, RIT consolidation improved CR rates from 41% to 91%

• Patients receiving induction chemotherapy as second-line (n = 12):
  • FCM/FC ± R: n = 1
  • CHOP/CVP ± R: n = 11
• Response rates from both induction treatments:
  • CR: 17% (n = 2)
  • PR: 83% (n = 10)
• In this population, RIT consolidation improved CR rates from 17% to 75%

• All consolidated patients (first- and second-line treatments; n = 46):
  • Response rates from both induction treatments:
    • CR: 35% (n = 16)
    • PR: 65% (n = 30)
  • Median PFS of patients consolidated after first-line therapy: 3.3 years
  • Median PFS of patients after chemosensitive relapse: 1.8 years
    • Comparison: P < 0.05
  • Median OS of patients consolidated after first-line therapy: 6.5 years
  • Median OS of patients after chemosensitive relapse: 2.2 years
    • Comparison: P < 0.05
  • Median PFS of patients achieving CR after first-line therapy and RIT: 5.8 years

Safety

• Deaths during the course of the study: n = 26
  • Due to early complications: 4.3% (n = 2)
  • Due to developing myelodysplastic syndrome: 10.8% (n = 5)
  • Due to MCL relapse or progression: 38% (n = 16)
• The entire protocol was well-tolerated
• Most common adverse events (AEs):
  • Bone marrow toxicity in the form of cytopenias:
    • Grade 1−2: 43% (n = 19)
    • Grade 3−4: 34% (n = 15)
  • Grade 3−4 thrombocytopenia and leukopenia were more frequent in patients treated with fludarabine-based regimens (P < 0.05)
  • Non-life threatening infections occurred in 48% of patients (n = 22) following RIT

Conclusions

• RIT seemed to be a feasible regimen for elderly or unfit patients with comorbidities, who are ineligible for high-dose chemotherapy and ASCT consolidation
• In this population, RIT consolidation following induction chemotherapy appears to confer durable responses and good PFS
• The regimen had a manageable toxicity profile but was worse after fludarabine-based regimens