Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Lymphoma: Chemotherapy, excluding Pre-Clinical Models: Aggressive NHL – MCL, Burkitt, T-cell
METHODS : The present MRD analysis was performed in a subgroup of randomized patients (n=178) of the 299 MCL patients (<66yrs) enrolled in the LyMa trial (Sept 2008 to Aug 2012). Briefly, all patients were previously untreated and received 4 courses of R-DHAP followed by ASCT using an R-BEAM conditioning regimen (n=257). After ASCT, patients were randomized between observation (obs) (n=120) versus Rituximab maintenance (RM) (n=119). The first planned interim-analysis, with a median follow-up of 40.6 months was presented at ASH 2014 and indicated superior PFS in the RM versus Obs arms (Le Gouill et al. ASH 2014). Sequential MRD monitoring was a predefined secondary objective and was performed throughout. At interim analysis the aim was to determine if peripheral blood (PB) and/or bone marrow (BM) MRD status, pre- and post ASCT, can predict patient outcome in terms of PFS according to RM or Obs. MRD was quantitatively assessed in PB and / or BM after induction, after ASCT by using gold standard EURO-MRD RQ-PCR assays and interpretation guidelines, targeted to clonal immunoglobulin gene rearrangements, in national reference laboratories. MRD data for survival analysis was generated from assays with a minimal sensitivity of at least 10-4. MRD status was assigned according to EURO-MRD interpretation guidelines. MRD negativity at a given time point was defined as absence of RQ-PCR amplification product in a given follow-up sample (minimal assay sensitivity of 10-4).
RESULTS: Among the 299 patients enrolled in the LyMa trial, MRD data in PB and / or BM was successfully generated pre- and/or post-ASCT phases, for a total of 178 randomized patients. Of the 61 out of 239 randomized patients without MRD data, 9 are ongoing and other reasons were no MRD target or MRD assay failure. Pre-ASCT MRD in BM and PB was negative in 66% (n=98) and 80% (n=120), of samples, respectively. Post-ASCT, MRD in BM and PB was found negative in 82% (n=122) and 95% (n=162), respectively. MRD status pre-ASCT in either BM or PB was predictive of longer PFS (respectively; p= 0.0451, p= 0.0016). In contrast, PB MRD status, post-ASCT failed to predict PFS while there was a trend for a better PFS for patients achieving MRD negativity in the BM (median PFS: NR vs 43.4 months ; p= 0.07 ). We next investigated patient outcome according to MRD status pre-ASCT and randomization arms. In BM and PB, respectively, 72% and 79% of patients in the obs arm were MRD negative compared to 59% and 80% in the RM arm, respectively. The estimated 3y-PFS for MRD pos/obs, neg/obs, pos/RM, neg/RM patients, according to BM and PB MRD status were: 61,6% (IC95%, 35.4-79.8) vs 83.9% (IC95%, 70.1-91.7) vs 86.2% (IC95%, 67.3-94.6) vs 91.8% (IC95%, 76.3-97.3) (p=0.0110) and 51.8% (IC95%, 24.4-73.6) vs 86.5% (IC95%, 73.5-93.4) vs 80% (IC95%, 50-93.1) vs 92.8% (IC95%, 81.6-97.3) ( p=0.0027), respectively.
CONCLUSION : Pre-ASCT MRD status in both BM and PB is an early predictor of PFS in younger MCL patients receiving ASCT. RM provides longer PFS regardless of MRD status pre-ASCT. Early sequential MRD monitoring at the pre-ASCT treatment phase thus offers strong potential for early clinical outcome prediction and MRD-guided, risk-adapted treatment in future MCL trials. Our preliminary results also suggest continued, clinically relevant, direct or indirect Rituximab-mediated anti-tumor activity, in rare residual circulating or ‘tissue-resident’ MCL cells.
Disclosures: Thieblemont: St. Louis Hospital, Paris, France: Employment . Casasnovas: Roche: Consultancy , Research Funding ; Takeda: Consultancy ; Gilead: Consultancy . Ribrag: Pharmamar: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Gilead: Membership on an entity’s Board of Directors or advisory committees ; Servier: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding .
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*signifies non-member of ASH