Sorafenib Combined with Chemotherapy and Donor Lymphocyte Infusion for Patients with FLT3 Wild-Type Acute Leukemia Relapsing after Allo-HSCT

Background

The efficacy for patients with acute leukemia (AL) who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a dismal prognosis, with the 2-year overall survival (OS) of only 20%. Therapeutic options for post-transplant relapse include chemotherapy, donor lymphocyte infusion (DLI), and second allo-HSCT. Despite such treatments, however, the efficacy is limited. Recent studies have shown sorafenib is also effective for AL patients without FLT3 mutations. The aim of this study was to investigate the efficacy of sorafenib combined with conventional therapies for AL patients without FLT3 mutations who relapsed after allo-HSCT.

Method

This study examined all consecutive AL patients without FLT3 mutations who experienced relapse after allo-HSCT at our hospital from November 2017 to April 2021. Patients with AL who relapsed after allo-HSCT were eligible for this study if they were FLT3 wild-type at the initial diagnosis and at relapse after allo-HSCT, and received sorafenib combined with conventional therapies as salvage induction therapy. Patients with chronic myelogenous leukemia with blast crisis and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) were excluded. We retrospectively evaluated the efficacy of sorafenib combined with chemotherapy and DLI as salvage induction and sorafenib combined with consolidation chemotherapy and interferon-ɑ (IFN-ɑ) as maintenance therapies for these patients. The evaluation indicators mainly include composite complete remission (CRc), OS, event-free survival (EFS) and graft-versus-host disease (GVHD).

Results

We identified forty-three AL patients without FLT3 mutations who relapsed after allo-HSCT were enrolled in this study. Primary diseases included AML (n =27) and ALL (n=16, including 9 acute B lymphoblastic leukemia and 7 acute T lymphoblastic leukemia). Twenty-six patients achieved composite complete remission (CRc) and 5 partial remission after salvage therapy. The rates of CRc and overall response were 60.5% (95%CI: 45.6%-73.6%) and 72.1% (57.3%-83.3%). With a median follow-up of 506 (range, 33 to 1944) days after relapse, 15 patients were alive, and 28 patients died. Causes of death included leukemia progression (n=21), infection (n=6), and aGVHD (n=1). The median OS and EFS were 16.9 (range, 1.1-64.8) months and 10.5 (range, 1.1-52.4) months, respectively.The 2-year overall survival and event-free survival were 44.2% (95% CI: 29.2%-58.2%) and 30.2% (17.4%-44.1%). The cumulative incidences of acute and chronic graft-versus-host disease after salvage therapy were 30.2% (95% CI: 17.2%-44.3%) and 23.3% (11.9%-36.8%). Multivariable analysis of risk factors for overall survival showed that no response at transplant and patient' s age ≥ 31 years were risk factors (P=0.001, HR 5.003; P=0.006, HR 3.263). The cumulative incidences of aGVHD and cGVHD after salvage therapy were 30.2% (95% CI: 17.2%-44.3%) and 23.3% (11.9%-36.8%), respectively. The mortality of GVHD after salvage therapy was 2.3% (95% CI: 0.2%-10.7%).

No relevant conflicts of interest to declare.