FDA approval summary: Crizotinib for pediatric and young adult patients with relapsed or refractory systemic anaplastic large cell lymphoma

Merino, Margret; Kasamon, Yvette L.; Li, Hongshan; Ma, Lian; Leong, Ruby; Zhou, Jiaxi; Reaman, Gregory H.; Chambers, Wiley A.; Richardson, Nicholas C.; Theoret, Marc R.; Pazdur, Richard; Gormley, Nicole

doi:10.1002/pbc.29602

Cited by 21 publications

(18 citation statements)

References 17 publications

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“…The ADVL0912 phase I/II study on 26 children receiving crizotinib for ALK-positive ALCL noted treatment-related grade ≥3 neutropenia (61.5%), lymphopenia, febrile neutropenia, myositis, and skin infection cases (3.8% each; no severe infection in the low-dose group) [ 144 ]. A commentary on ADVL0912 stated that rates of severe cytopenias may rise with exposure and that upper respiratory infections are commonly seen with crizotinib treatment (31%; no severe case) [ 145 ]. Combination of crizotinib with cytotoxic chemotherapy in the ADVL1212 phase I study for children with refractory solid tumors or ALCL demonstrated high rates of severe infections (20.5%) and febrile neutropenia (38.5%) [ 146 ].…”

Section: Tyrosine Kinase Inhibitors (Tkis)mentioning

confidence: 99%

Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas

Kyriakidis

Mantadakis

Stiakaki

et al. 2022

Cancers

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The aim of this review is to highlight mechanisms of immunosuppression for each agent, along with pooled analyses of infectious complications from the available medical literature. Rituximab confers no increase in grade ≥3 infectious risks, except in the case of patients with advanced-stage non-Hodgkin lymphoma. Gemtuzumab ozogamicin links with high rates of grade ≥3 infections which, however, are comparable with historical cohorts. Pembrolizumab exhibits a favorable safety profile in terms of severe infections. Despite high rates of hypogammaglobulinemia (HGG) with blinatumomab, low-grade ≥3 infection rates were observed, especially in the post-reinduction therapy of relapsed B-acute lymphoblastic leukemia. Imatinib and nilotinib are generally devoid of severe infectious complications, but dasatinib may slightly increase the risk of opportunistic infections. Data on crizotinib and pan-Trk inhibitors entrectinib and larotrectinib are limited. CAR T-cell therapy with tisagenlecleucel is associated with grade ≥3 infections in children and is linked with HGG and the emergence of immune-related adverse events. Off-label therapies inotuzumab ozogamicin, brentuximab vedotin, and venetoclax demonstrate low rates of treatment-related grade ≥3 infections, while the addition of bortezomib to standard chemotherapy in T-cell malignancies seems to decrease the infection risk during induction. Prophylaxis, immune reconstitution, and vaccinations for each targeted agent are discussed, along with comparisons to adult studies.

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Section: Tyrosine Kinase Inhibitors (Tkis)mentioning

confidence: 99%

Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas

Kyriakidis

Mantadakis

Stiakaki

et al. 2022

Cancers

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“…In the case of the approval of naxitamab, characterization of DOR was limited by lack of prespecified disease assessments following treatment discontinuation, receipt of further treatment and follow-up at local institutions, and by the administration of subsequent anticancer therapy following onset of response but prior to demonstration of disease progression in some patients [4]. The approval of crizotinib for sALCL also faced limitations in the assessment of DOR as most patients proceeded to transplant [10 ▪ ]. In both these examples, DOR as calculated may be a conservative assessment of the treatment effect, and the review teams determined that sufficient information was provided to support an assessment of DOR, despite limitations.…”

Section: Discussionmentioning

confidence: 99%

“…Efficacy evaluation was based on ORR and DOR observed in 26 patients with sALCL ages 3–20 years old (Table 1) [9]. The assessment of DOR, critical to assessment of ORR as a clinical endpoint, was limited by more than half of patients proceeding to hematopoietic stem cell transplantation (HSCT); data on DOR in the patients who did not proceed to HSCT supported durability of responses [10 ▪ ]. In this case, the review team considered the biologic similarity of the disease in young adults and the inclusion of some young adults in the study population to support extension of the pediatric indication to include young adults [10 ▪ ].…”

Section: Crizotinibmentioning

confidence: 99%

FDA regulatory considerations for the review of drugs intended to treat pediatric cancers and rare tumors

Bradford

Singh

Donoghue

2022

Current Opinion in Pediatrics

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Purpose of reviewWe describe select recent FDA approvals in pediatric cancers and rare tumors, and the unique regulatory considerations raised by each application. Recent findingsThe approvals of naxitamab, selumetinib, selpercatinib, and crizotinib for pediatric and adolescent patients between April 2020 and January 2021 all represented first FDA approvals in their respective pediatric or adolescent populations. In addition, all represent approvals of targeted therapies administered in select patient populations, and were based on overall response rate (ORR) and duration of response (DOR) data in single-arm trials.

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“…Similar results were observed for small molecules. Crizotinib (Xalkori), a multitarget TKI targeting ALK, ROS1, and MET, has been approved for treating relapsed refractory ALCL in children and young adults (24)(25)(26)(27)(28). Approval was obtained based on a high overall response rate (88%), complete response rate (81%), and duration of response, with 67% of patients not undergoing stem cell transplantation reaching at least 6 months of CR.…”

Section: Alk Signaling In Anaplastic Large Cell Lymphomamentioning

confidence: 99%

Tyrosine kinases in nodal peripheral T-cell lymphomas

Piccaluga

Cascianelli²,

Inghirami

2023

Front. Oncol.

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Nodal peripheral T-cell lymphomas (PTCL) are uncommon and heterogeneous tumors characterized by a dismal prognosis. Targeted therapy has been proposed. However, reliable targets are mostly represented by a few surface antigens (e.g., CD52 and CD30), chemokine receptors (e.g., CCR4), and epigenetic gene expression regulation. In the last two decades, however, several studies have supported the idea that tyrosine kinase (TK) deregulation might be relevant for both the pathogenesis and treatment of PTCL. Indeed, they can be expressed or activated as a consequence of their involvement in genetic lesions, such as translocations, or by ligand overexpression. The most striking example is ALK in anaplastic large-cell lymphomas (ALCL). ALK activity is necessary to support cell proliferation and survival, and its inhibition leads to cell death. Notably, STAT3 was found to be the main downstream ALK effector. Other TKs are consistently expressed and active in PTCLs, such as PDGFRA, and members of the T-cell receptor signaling family, such as SYK. Notably, as in the case of ALK, STAT proteins have emerged as key downstream factors for most of the involved TK.

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FDA approval summary: Crizotinib for pediatric and young adult patients with relapsed or refractory systemic anaplastic large cell lymphoma

Cited by 21 publications

References 17 publications

Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas

Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas

FDA regulatory considerations for the review of drugs intended to treat pediatric cancers and rare tumors

Tyrosine kinases in nodal peripheral T-cell lymphomas

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