The Prognostic Value of Minimal Residual Disease (MRD) after Salvage Therapy in Patients (Pts) with Relapsed or Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (ALL)

Introduction: MRD positivity after induction/consolidation therapy in pts with de novo ALL has been shown to carry a very negative impact on outcome. However, the significance of MRD status in the salvage setting has not been extensively studied. Methods : We evaluated 130 pts with R/R B-cell ALL pts who received first (n=68), or second (n=62), salvage therapy between 2010 and 2015. Salvage therapies included single agent inotuzumab ozogamicin (INO; n=75), blinatumomab (n=20), or INO in combination with mini-hyper-CVD (n=35) [Jabbour E et al; EHA 2015]. Of the 130 pts treated, 78 (60%) responded and were assessed for MRD by six-color flow cytometry on marrow samples with a sensitivity of 0.01%. Morphologic responses were defined as follows, complete response (CR); disappearance of all disease with neutrophils ≥ 1.0 X 109/L, platelet > 100 X 109/L and blasts ≤ 5%, CRp; CR without platelet recovery, CRi; CR without platelet and/or neutrophil recovery. Results : The clinical characteristics of the 78 responding pts with R/R ALL are summarized in Table 1. Overall, MRD negativity was achieved at response in 41 pts (53%). Among the 41 pts who responded to single agent INO (12 CR, 26 CRp, 3CRi), 17 (41%) achieved a negative MRD status. Among the 11 pts who responded to blinatumomab (9 CR, 2Cri), 8 (73%) achieved a negative MRD status. Among the 26 pts who responded to INO in combination with mini-HCVD (21 CR, 4 CRp, 1CRi), 16 (62%) achieved a negative MRD status. Forty-four pts received allogeneic stem cell transplantation (ASCT): of those, 21 pts were MRD negative and 23 pts were MRD positive at the time of response. Median follow-up was 19 months (2-55). Overall, there was a trend for more durable morphologic responses in MRD negative pts compared with MRD positive pts: the median complete remission durations (CRD) were 17 months and 8 months, with a 2-year CRD rate of 47% and 28% respectively (Table 2). The median event-free survival (EFS) was 12 and 6 months, respectively; the 2-year EFS rates were 32% and 8%, respectively. Similarly, there was a trend for better overall survival (OS) with a median of 17 months and 9 months for pts with negative and positive MRD, respectively; the 2-year OS rates were 36% and 27%, respectively. No difference in outcome was reported whether pts were censored or not at the time of ASCT. Conclusion : In pts with R/R ALL, the achievement of negative MRD in addition to the morphologic response confers an improvement, although not statistically significant, in response duration and survival. Larger number of pts with longer follow-up is needed to validate these findings. | | N (%)/Median [range] | | --------------------------------- | -------------------- | | Age (years) | 38 [18-87] | | Sex (Male) | 50 (64) | | Performance Status | 1 [1-3] | | WBC (x 109/L) | 3 [0.3-38] | | % PB Blasts | 0 [0-83] | | % BM Blasts | 60 [8-97] | | Cytogenetics | | | Diploid | 20 (26) | | t(9;22) | 4 (5) | | t(4;11) | 7 (9) | | Miscellaneous | 39 (50) | | Not done/ Insufficient metaphases | 8 (10) | | Salvage | | | Inotuzumab Ozogamicin | 41 (53) | | Blinatumomab | 11 (14) | | Inotuzumab Ozogamicin + mini-HCVD | 26 (33) | | Number of prior therapies | | | 1 prior therapy | 46 (59) | | 2 prior therapies | 32 (41) | Table 1. Clinical Characteristics of Pts (n=78) | | MRD Negative (n=41) | MRD Positive (n=37) | p | | ------------------- | ------------------- | ------------------- | ---- | | CR | 24 | 18 | n/a | | CRp | 16 | 14 | n/a | | CRi | 1 | 5 | n/a | | CRD, median (m) | 17 | 8 | 0.63 | | 2-year CRD rate (%) | 47 | 28 | | EFS, median (m) | 12 | 6 | 0.06 | | 2-year EFS rate (%) | 32 | 8 | | OS, median (m) | 17 | 9 | 0.18 | | 2-year OS rate (%) | 36 | 27 | Table 2. Response Rates and Survival by MRD Status Disclosures Cortes: Teva: Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BerGenBio AS: Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. DiNardo: Novartis: Research Funding.