Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia

Wayne, Alan S.; Shah, Nirali N.; Bhojwani, Deepa; Silverman, Lewis B.; Whitlock, James A.; Stetler‐Stevenson, Maryalice; Sun, Wei‐Zen; Liang, Meina; Yang, Jie; Kreitman, Robert J.; Lanasa, Mark C.; Pastan, Ira

doi:10.1182/blood-2017-02-749101

Cited by 64 publications

(74 citation statements)

References 33 publications

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“…27 HA22 was administered in a phase 1 study in children with relapsed refractory hematological malignancies at a dose between 5 and 40 g/kg IV every other day for 12 days. 28 Of the 17 evaluable patients, 30% achieved a CR (24%), with an ORR of 68%. The dose limiting toxicity (DLT) was a capillary leak syndrome seen in 2 of 7 patients in the 30 g/kg dose level.…”

Section: Bl22 and Ha22mentioning

confidence: 93%

The use of novel monoclonal antibodies in the treatment of acute lymphoblastic leukemia

DeAngelo

2015

Hematology

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Regardless of age, patients with relapsed or refractory acute lymphoblastic leukemia (ALL) have extremely poor outcomes. The success of reinduction chemotherapy remains dismal, because complete remission rates are low and seldom durable. Clearly, new and novel strategies are needed to improve the outcome of patients with relapsed or refractory ALL. Patients with early relapse, especially those still receiving chemotherapy, tend to have a much poorer outcome and are often chemotherapy resistant. Although high-dose approaches may overcome chemotherapy resistance, long-term disease-free and overall survival remains limited. Several approaches have been used to target antigens, including cluster of differentiation (CD) 19, CD20, CD22, and CD52, on the surface of the malignant lymphoblast with striking efficacy. This review will focus on the clinical application of the major classes of antibodies, including naked antibodies, drug-antibody conjugates, immunotoxins, and T cell-engaging bispecific antibodies. Hopefully, these novel monoclonal antibodies will result in a significant improvement in the outcome of patients with relapsed or refractory ALL.There has been tremendous progress in the treatment of patients with acute lymphoblastic leukemia (ALL). Currently, pediatric patients with ALL have a complete remission (CR) rate of 95% with estimated 5-year event-free survival (EFS) rates of 80%-85%. 1 The results of adult patients with ALL have not kept pace with their pediatric counterparts. In comparison, although the current adult regimens have CR rates of ϳ85%, the 3-year disease-free survival (DFS) and overall survival (OS) rates remain Ͻ45%. 2,3 Pediatric inspired regimens are currently being explored for young adult patients, which has led to improvements in the EFS and OS rates compared with historical controls. [4][5][6] Despite the high CR rates in both pediatric and adult patients with ALL, relapse is an insurmountable problem for many individuals. The higher rate of relapse in adult patients with ALL is likely attributable to higher risk disease. For example, more adult patients have adverse cytogenetics, such as the Philadelphia chromosome or translocations involving the mixed lineage leukemia gene on 11q23, persistent minimal resistant disease (MRD), and poor tolerance of the intense and prolonged chemotherapy protocols. Salvage chemotherapy regimens have shown only modest activity in patients with relapsed or refractory ALL with median remission duration of only 2-7 months (Table 1). 7,8 The outcome is particularly poor in patients who relapse while on therapy or with CR duration (CRD) of Ͻ24 months. In this group of patients, long-term survival is Ͻ5%.The success of long-term outcomes for patients with relapsed or refractory ALL involves the ability to obtain a CR. However, for the majority of adults, despite the ability to achieve a CR, these are seldom durable in patients with refractory or relapsed disease. 7,8 Therefore, the ability to achieve a CR and to have the opportunity to obtain a hematopoieti...

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Section: Bl22 and Ha22mentioning

confidence: 93%

The use of novel monoclonal antibodies in the treatment of acute lymphoblastic leukemia

DeAngelo

2015

Hematology

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“…However, it displays a higher affinity for CD22. Nineteen heavily pre-treated children and young adults with relapsed/ refractory CD22 + ALL were treated with CAT-8015 [145]. Four patients achieved CR, one had a partial response and eight showed hematological improvement.…”

Section: Inotuzumab Ozogamicinmentioning

confidence: 98%

Novel approaches to pediatric leukemia treatment

Thomas¹

2015

Expert Review of Anticancer Therapy

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Despite remarkable improvements in the treatment of pediatric acute leukemia (AL) over the last decades, relapse still carries a poor prognosis with significant morbidity and mortality. Novel targeted therapies are currently being investigated in an attempt to reduce adverse events and improve survival outcomes. This review summarizes recent data from the literature regarding advances in drug discovery based on biological evidence and the novel targeted drug therapies for childhood AL. Significant challenges still remain for novel drug development in childhood AL. However, first results combined with a large number of new agents currently being investigated are very encouraging. Furthermore, therapeutic advances will depend upon combination strategies using the specific action of each agent and their complementary effects on leukemia cells.

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“…На данный момент проводится исследование фазы I моксету-момаба при лечении детских CD22+ гемобластозов. По предварительным результатам, полученным в группе из 17 подлежащих оценке пациентов, у 4 (24%) отмечен полный ответ, у 1 (6%) -частич-ный ответ и у 7 (41%) пациентов -сокращение чис-ла бластных клеток в периферической крови более чем на 50% [59]. В целом наблюдаемые токсические эффекты были слабыми и обратимыми, правда, у нескольких пациентов наблюдался синдром гипер-цитокинемии, который оказался дозолимитирующим.…”

Section: Cd22unclassified

Prospects of targeted therapy of acute leukemias in children

Rumyantsev¹

2017

VGOIP

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Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia

Abstract: Key Points A phase 1 trial of the anti-CD22 immunotoxin moxetumomab pasudotox was conducted in children with ALL. A 32% objective response rate was observed, including 11 composite complete responses (23%), 5 of which were minimal residual disease negative.

Cited by 64 publications

References 33 publications

The use of novel monoclonal antibodies in the treatment of acute lymphoblastic leukemia

The use of novel monoclonal antibodies in the treatment of acute lymphoblastic leukemia

Novel approaches to pediatric leukemia treatment

Prospects of targeted therapy of acute leukemias in children

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