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Review Hematologic Malignancies
Updates in Adult Acute Lymphoblastic
Leukemia—Current Status of Antigen-
targeted Treatments and Immunotherapy
Hospices Civils de Lyon, Hematology Department, Lyon-Sud Hospital, Pierre Bénite, France
T he outcomes of adult acute lymphoblastic leukemia (ALL) remain inferior to those observed in pediatric populations. Targeted therapy with
monoclonal antibodies and immunotherapy represents the most promising new way to fight ALL without significant additive toxicity. Since
the use of rituximab in combination chemoimmunotherapy for treatment of B cell lineage ALL, a number of other monoclonal antibodies
are under investigation for the treatment of this disease. Deep molecular remissions with anti-CD19- and anti-CD22-directed therapy have been
shown in relapsed/refractory (R/R) disease, allowing for the opportunity to transplant. Blinatumomab is the first antigen-directed treatment
approved for use in R/R ALL. Adoptive cellular therapy with human T cells genetically engineered to express CD19 redirected chimeric antigen
receptors (CARs) has also recently demonstrated efficacy in patients with B cell lineage ALL. In this article, we review the therapeutic implications,
primary results, and current status of antigen-targeted treatments and immunotherapy in adult B cell lineage ALL.
Keywords Acute lymphoblastic leukemia, monoclonal
antibodies, prognosis, blinatumomab, chimeric
antigen receptor (CAR) T cells, inotuzumab
ozogamicin, rituximab, epratuzumab
Disclosure: Xavier Thomas has nothing to
declare in relation to this article. No funding was
received in the publication of this article.
Compliance with Ethics: This study involves a review of
the literature and did not involve any studies with human
or animal subjects performed by any of the authors.
Authorship: All named authors meet the International
Committee of Medical Journal Editors (ICMJE) criteria
for authorship of this manuscript, take responsibility
for the integrity of the work as a whole, and have
given final approval to the version to be published.
Open Access: This article is published under the
Creative Commons Attribution Noncommercial License,
which permits any non-commercial use, distribution,
adaptation and reproduction provided the original
author(s) and source are given appropriate credit.
Received: July 3, 2017
Accepted: September 7, 2017
Citation: Oncology & Hematology Review,
2017;13(2):92–9 Corresponding Author: Xavier Thomas, Hospices
Civils de Lyon, Hematology Department, Lyon-Sud
Hospital, Bât. 1G, 165 chemin du Grand Revoyet, 69495
Pierre Bénite, France. E: firstname.lastname@example.org
Acute lymphoblastic leukemia (ALL) is of B cell precursor lineage (BCP-ALL) or, less commonly, T cell
precursor lineage (T-ALL), which comprise multiple subtypes defined by structural chromosomal
alterations that are initiating lesions, with secondary somatic DNA copy number alterations and
sequence mutations that contribute to leukemogenesis. Survival rates for ALL have steadily improved
in children, such that more than 85% of children can expect to be cured with current cytotoxic
therapies. Unfortunately, the same increases have not been demonstrated in adult patients. Despite
high rates of complete remission (CR) (80–90%), the cure rates are only 40–50%, because of relapses. 1
One approach to improving outcomes in adult ALL involves intensification of existing chemotherapy
combinations or the addition of chemotherapeutic agents. 2 The results of allogeneic hematopoietic
stem cell transplantation (HSCT) for adults with ALL in first-line therapy have also improved
significantly over time, 3 but it is unlikely that the sole intensification of regimens can continue to
improve prognosis substantially. Intensifying chemotherapy may reduce the incidence of resistance,
but at the cost of increased toxicities. Outcomes remain particularly poor in relapsed/refractory (R/R)
patients. Response rates after salvage treatment range from 18–45% and median survival times from
2–8 months, with less than 10% survival after 5 years. 4–9 In this setting, allogeneic HSCT is the only
curative option, but this can only be achieved in a subgroup of patients. 4,5,8 A retrospective analysis of
1,706 adult patients with Philadelphia chromosome-negative R/R BCP-ALL from 11 study groups and
large centers was recently conducted in order to provide detailed reference outcomes for this patient
population. 10 The overall CR rate after first salvage was 40%, ranging from 35–41% across disease
status categories (primary refractory, relapsed with or without prior transplant), and was lower after
second (21%) or further (11%) salvage. The 3-year survival rates range from 2–5%.
Thus, new treatment options are needed for this patient population. This, combined with a better
understanding of disease pathogenesis has led to major advances in drug development and reassessment
of risk stratification. 11 The landscape of treatment is currently rapidly changing, ranging from the application
of precision genomic medicine in subsets of ALL to the delivery of novel immunotherapeutic approaches.
Emerging therapies in the frontline and salvage settings offer the promise of improved response rates
and opportunities for long-term survival, with the potential for less toxicity than chemotherapy. 12–14
In this review, we will discuss the use of monoclonal antibodies and novel immunotherapeutic
approaches in ALL, including bispecific T cell-engaging molecules and chimeric antigen receptor
(CAR) T cells.
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