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

Abstract

Background Minimal residual disease (MRD) assessment predicts survival in newly diagnosed acute lymphoblastic leukemia (ALL). Its significance in relapsed/refractory ALL is less clear. Methods We identified 78 patients with relapsed/refractory B-ALL who achieved morphologic response with inotuzumab ozogamicin (n=41), blinatumomab (n=11) or mini-hyper-CVD plus inotuzumab (HCVD+ino; n=26) given in either salvage 1 (S1; n=46) or salvage 2 (S2; n=32) and who had 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 a longer EFS (median 18 months versus 7 months; 2-year EFS rate 46% versus 17%; P=0.06) and OS (median 27 months versus 9 months; 2-year OS 52% versus 36%; P=0.15). EFS and OS were similar in S2 regardless of MRD response. Among MRD-negative patients who underwent allogeneic stem cell transplant (SCT), EFS and OS were superior for those who underwent SCT in S1 rather than in S2 (P=0.003 and P=0.04, 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 MRD status.

Chemoimmunotherapy with inotuzumab ozogamicin combined with mini‐hyper‐CVD, with or without blinatumomab, is highly effective in patients with Philadelphia chromosome–negative acute lymphoblastic leukemia in first salvage

“…The favorable outcomes of these patients are in line with our previous report, which showed that ASCT for patients with morphologic and flow MRD responses in salvage 1 resulted in the best outcomes, with a cure rate approaching 50%. 9 This is in contrast to the outcomes of patients treated in salvage 2, where the achievement of a flow MRD response and subsequent ASCT had no impact on survival.…”

“…6 Better results were obtained in patients treated earlier (salvage 1 vs salvage 2 or later) and in patients with a minimal disease burden; such patients can experience long-term survival. [8][9][10][11] The addition of inotuzumab ozogamicin as targeted immunotherapy to effective low-intensity chemotherapy in patients with R-R ALL has shown promising results with an overall response rate of 80% and a median survival of 11 months versus 6 months with single-agent inotuzumab ozogamicin in similar patient populations. 10 Such a strategy may translate into a significant long-term survival benefit when it is used for patients in first salvage.…”

Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study

“…In another analysis, patients who achieved an MRD response with inotuzumab ozogamicin, blinatumomab, or mini‐hyperfractionated cyclophosphamide, vincristine and doxorubicin plus inotuzumab in first salvage therapy had better outcomes compared with those in second salvage therapy. A numerical improvement in OS after HSCT versus no HSCT was noted among patients treated in first salvage therapy with MRD response, although this difference lacked statistical significance ( P = .28) …”

“…A numerical improvement in OS after HSCT versus no HSCT was noted among patients treated in first salvage therapy with MRD response, although this difference lacked statistical significance (P = .28). 22 To our knowledge, the role of HSCT after MRD remission in patients with R/R ALL remains unclear.…”

Hyper-CVAD + epratuzumab as a salvage regimen for younger patients with relapsed/refractory CD22-positive precursor B-cell acute lymphocytic leukemia

“…12 However, the positive impact of MRD negativity reported recently for ALL patients in first salvage 15 was not observed here. The partial efficacy of the Cheprall regimen in a population with such a poor prognosis suggests that epratuzumab should be tested in first-line schedules, since it may also contribute to decreasing the level of MRD, especially before allogeneic hematopoietic stem cell transplantation, with the hope of increasing patients' survival.…”