Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma

Abstract

Y-ibritumomab-tiuxetan (Zevalin) to the highdose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), eventfree survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as

Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

“…Similarly, in the Nordic MCL3 study, 25 MRD status after ASCT was strongly prognostic for PFS, with 4-year PFS of about 38% (median PFS,~3 years) in 18 patients who had MRD-positive PB or BM compared with about 88% in 89 MRD-negative patients. The prognostic value of MRD status after ASCT was stronger than that before ASCT and was also seen after adjustment for MIPI, Ki-67 index, computed tomography status before ASCT and positron emission tomography (PET) status before ASCT, with adjusted HRs of 5.0 for PFS and 4.8 for OS.…”

“…In the Nordic MCL3 study, similar to the MCL Younger trial, 53% molecular remissions were observed by qualitative nested PCR in patients with clinical remission after 5 alternating R-CHOP/R-HA cycles. 25 The investigation of MRD during induction treatment indicates that the higher intensity of modern regimens is reflected in a rapid tumor cell clearance in PB and BM. Therefore, MRD assessment seems to be well suited for precisely monitoring the impact of different treatment schemes or individual drugs on tumor cell clearance.…”

“…25 Similarly, in an interim analysis of the LYMA trial by the Lymphoma Study Association (LYSA), patients in molecular remission after 4 cycles of R-DHAP who received transplants had superior PFS compared with patients who were MRD positive before ASCT; this prognostic effect seemed to be more prominent in the patients observed after ASCT (3-year PFS of MRD-negative vs MRD-positive patients before ASCT: 87% vs 52% in PB; 84% vs 62% in BM) compared with patients who were treated with rituximab maintenance after ASCT (93% vs 80% in PB; 92% vs 86% in BM). 28 Several smaller studies have also shown the prognostic value of MRD status after various induction immunochemotherapies and before high-dose consolidation.…”

“…3,33 In the Nordic MCL3 study, ASCT raised the percentage of MRDnegative patients in PB and/or BM from 53% after alternating R-CHOP/R-HA therapy to 83%. 25 In an interim analysis of the LYMA trial, ASCT increased MRD-negative rates among patients in clinical remission after 4 cycles of R-DHAP from 80% to 95% in PB and from 66% to 82% in BM. 28 These results reinforce the observation that the additional effect of high-dose consolidation on tumor cell clearance is dependent on the power of the preceding induction treatment.…”

Long-term follow-up of 90Y-ibritumomab-tiuxetan (90YIT) in the conditioning of autologous hematopoietic transplantation for indolent and mantle cell lymphomas in a single French center

“…Since 2006, several studies have described promising results in relapsed or refractory NHLs with heterogeneous cohorts including iNHLs but also a majority of aggressive lymphomas. [1][2][3][4][5] Only one phase II prospective study in indolent lymphomas showed a benefit of 90 YIT in association with BEAM (Z-BEAM) as intensive therapy. 6 There is a lack of data about the efficacy and safety of Z-BEAM conditioning regimen in iNHLs especially because of short follow-up in the published data.…”