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. 2017 Jan 1;123(2):294-302.
doi: 10.1002/cncr.30264. Epub 2016 Sep 7.

Differential impact of minimal residual disease negativity according to the salvage status in patients with relapsed/refractory B-cell acute lymphoblastic leukemia

Elias Jabbour  1 , Nicholas J Short  2 , Jeffrey L Jorgensen  3 , Musa Yilmaz  1 , Farhad Ravandi  1 , Sa A Wang  3 , Deborah A Thomas  1 , Joseph Khoury  3 , Richard E Champlin  4 , Issa Khouri  4 , Partow Kebriaei  4 , Susan M O'Brien  5 , Guillermo Garcia-Manero  1 , Jorge E Cortes  1 , Koji Sasaki  1 , Courtney D Dinardo  1 , Tapan M Kadia  1 , Nitin Jain  1 , Marina Konopleva  1 , Rebecca Garris  1 , Hagop M Kantarjian  1
Affiliations

Differential impact of minimal residual disease negativity according to the salvage status in patients with relapsed/refractory B-cell acute lymphoblastic leukemia

Elias Jabbour et al. Cancer. .

Abstract

Background: Minimal residual disease (MRD) assessment predicts survival for patients with newly diagnosed acute lymphoblastic leukemia (ALL). Its significance in relapsed/refractory ALL is less clear.

Methods: This study identified 78 patients with relapsed/refractory B-cell ALL who achieved a morphologic response with inotuzumab ozogamicin (n = 41), blinatumomab (n = 11), or mini-hyperfractionated cyclophosphamide, vincristine, and doxorubicin plus inotuzumab (n = 26) during either salvage 1 (S1; n = 46) or salvage 2 (S2; n = 32) and had undergone an MRD assessment by multiparameter flow cytometry at the time of remission.

Results: MRD negativity was achieved in 41 patients overall (53%). The MRD negativity rate was 57% in S1 and 47% in S2. Among patients in S1, achieving MRD negativity was associated with longer event-free survival (EFS; median, 18 vs 7 months; 2-year EFS rate, 46% vs 17%; P = .06) and overall survival (OS; median, 27 vs 9 months; 2-year OS, 52% vs 36%; P = .15). EFS and OS were similar in S2, regardless of the MRD response. Among MRD-negative patients who underwent allogeneic stem cell transplantation (SCT), EFS and OS were superior for those who underwent SCT in S1 rather than S2 (P = .003 and P = .04, respectively). Patients in S1 who achieved MRD negativity and subsequently underwent SCT had the best outcomes with a 2-year OS rate of 65%.

Conclusions: Patients with relapsed/refractory ALL who achieve MRD negativity in S1 can have long-term survival. Patients in S2 generally have poor outcomes, regardless of their MRD status. Cancer 2017;123:294-302. © 2016 American Cancer Society.

Keywords: acute lymphoblastic leukemia; blinatumomab; inotuzumab; minimal residual disease; refractory; relapsed.

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Figures

Figure 1
Figure 1. Study population
Figure 2
Figure 2. Outcomes by minimal residual disease (MRD) response
(A) Event-free survival (EFS) and (B) overall survival (OS).
Figure 3
Figure 3. Outcomes by minimal residual disease (MRD) response, stratified by salvage status
(A) Event-free survival (EFS) and (B) overall survival (OS).
Figure 4
Figure 4. Outcomes of patients after first salvage treatment, stratified by minimal residual disease (MRD) status and stem cell transplantation (SCT)
(A) Event-free survival (EFS) and (B) overall survival (OS).
Figure 5
Figure 5. Outcomes of patients after second salvage treatment, stratified by minimal residual disease (MRD) status and stem cell transplantation (SCT)
(A) Event-free survival (EFS) and (B) overall survival (OS).
See this image and copyright information in PMC

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