Treatment of Adult Patients with Relapsed/Refractory B-Cell Philadelphia-Negative Acute Lymphoblastic Leukemia

Abstract

The majority of adult patients affected by B-cell acute lymphoblastic leukemia (B-ALL) will relapse after an initial response, while approximately 20% will display primary resistant disease. Patients suffering from relapsed/refractory BALL have a very poor outcome. Allogeneic hematopoietic cell transplantation (HCT) still represents the only curative approach, but is not so frequently feasible, because of patient's fitness, donor availability, and the ability to achieve a remission prior to HCT. The estimated remission rates with conventional cytotoxic agents are around 30%, but they are short-lived. These disappointing results led to the introduction of new immunologic-based treatments-blinatumomab and inotuzumab. They produced a substantial improvement in terms of response rates, with the ability, in most cases, to induce a minimal residual disease (MRD)-negative status. Similarly, T cells engineered to express a CD19-specific chimeric antigen receptor (CAR-T) have yielded sensational results among patients with relapsed/refractory BALL , with unexpectedly high MRD-negative complete remissions rates. However, the first studies looking at long-term outcomes after CART infusions told us that a significant fraction of such responses are not durable, and may benefit from a consolidation approach such as an allogeneic HCT.

Measurable residual disease (MRD) testing for acute leukemia in EBMT transplant centers: a survey on behalf of the ALWP of the EBMT

“…Over the last decade, persistence of detectable measurable residual disease (MRD) after intensive chemotherapy has proven to be a key prognostic factor in adult patients with acute leukemia. Specifically, in the setting of acute lymphoblastic leukemia (ALL), MRD monitoring has become an important parameter to guide therapeutic strategy including indication or not of performing an allogeneic hematopoietic stem cell transplantation (allo-HCT) in first complete remission [1,2]. Indeed, in a recent meta-analysis achievement of MRD negativity was strongly associated with better overall survival (OS) [3].…”

The evolving role of allogeneic haematopoietic cell transplantation in the era of chimaeric antigen receptor T‐cell therapy

“…Novel immunotherapies such as blinatumomab [CD19‐CD3 bispecific T‐cell engager (TCE)] or inotuzumab ozogamicin [CD22‐ozogamicin antibody‐drug conjugate (ADC)] have become new standards in this setting. CR rates in these patients after salvage therapies are approximately 30–40% with less than half being eligible for subsequent allo‐HCT 20–22 . In pivotal studies, the rate of consolidative allo‐HCT was 24% after blinatumomab and 41% after inotuzumab ozogamicin.…”

CD22 Expression in B-Cell Acute Lymphoblastic Leukemia: Biological Significance and Implications for Inotuzumab Therapy in Adults

“…Adult ALL at diagnosis tends to be higher risk, and approximately 20% of adult patients experience unfavorable outcomes. After an initial period of complete remission, adult patients typically develop chemoresistance and disease relapse [1,2]. Since this contrasts so strongly with the impressive rate of total remission in pediatric patients, hematologists have begun using drugs from pediatric therapeutic protocols for adult patients as well.…”