MCL

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
References
  1. Jurczak W. et al. Consolidation with 90Y ibritumomab tiuxetan radioimmunotherapy in mantle cell lymphoma patients ineligible for high dose therapy: results of the phase II multicentre Polish Lymphoma Research Group trial, after 8-year long follow-up. Leuk Lymphoma. 2019 Apr 9:1-8. DOI: 10.1080/10428194.2019.1602261 [Epub ahead of print].

     
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