Vibutuximab has great potential in newly diagnosed children with cHL

Professor Monika L.
Metzger and others recently reported the results of an open-label, single-arm, multi-center clinical trial for newly diagnosed classic Hodgkin’s lymphoma (cHL) patients ≤18 years of age.
The clinical study aims to evaluate Wibutor.
The efficacy and safety of cilimab combined with chemotherapy.

Research background and objectives Children with HL under the current combined treatment model, the long-term event-free survival (EFS) rate is about 90%, and the overall survival (OS) rate is 98%-99%.

Even after the risk stratification of high-risk patients, the combination of chemotherapy and affected field radiotherapy (IFRT) can still achieve a 5-year EFS of 85%-94%.

In recent years, the focus of clinical research on children with HL has been to select the appropriate intensity of therapy through risk stratification, hoping to avoid radiotherapy as much as possible while maintaining an excellent cure rate, in order to reduce the long-term toxicity of patients.

Verbutuximab is an antibody-drug conjugate (ADC) that targets CD30.
It has been approved for use in adult cHL, but its efficacy and safety in children and adolescents are still unclear.
.

Based on this, the researchers conducted the HLHR13 trial to evaluate the efficacy and safety of verbutoxib combined with chemotherapy in newly diagnosed cHL patients ≤18 years of age.

Research methods The study included cHL patients ≤18 years of age who were newly diagnosed with immunohistochemical detection of CD30 and Ann Arbor stage ⅡB, ⅢB or Ⅳ.

All patients received chemotherapy including 2 cycles of AEPA (vebutuximab, etoposide, prednisone and doxorubicin), followed by 4 cycles of CAPDac (cyclophosphamide, vebutuximab) , Prednisone and dacarbazine).

After receiving 2 cycles of AEPA treatment, the patients received PET/CT and enhanced CT scan or MRI to assess their early response to treatment (ERA).

Patients whose ERA achieved complete remission (CR) did not receive radiotherapy in subsequent lymph nodes, while patients who did not achieve CR received additional lymph node radiotherapy after the entire chemotherapy was completed, further reducing the target lesions receiving radiotherapy.

The primary endpoint of the study is the CR rate at the time of ERA in patients, and compare EFS and OS with the use of Stanford V (prednisone, nitrogen mustard, doxorubicin, vincristine, etoposide, bleomycin and vinca Base) for comparison with the historical control group.

Research results The trial recruited 77 eligible cHL patients from August 8, 2013 to July 9, 2018.

The median age of patients at diagnosis was 16 years, 51% were women, and 65% were white; the most common histological subtype was nodular sclerosis (77%), and most patients were stage IV (59%).

There was no significant difference in demographic characteristics between the HLHR13 trial and the historical control group.

The HLHR13 trial recruited more patients in stage IIIB (25% vs 14%) and stage IVB (43% vs 37%) (P=0.
046).

A total of 27 (35%) patients in the trial achieved CR at ERA and did not receive radiotherapy.

Patients who did not reach CR at ERA received single residual lymph node radiotherapy (25.
5 Gy).

At a median follow-up time of 3.
4 years, the patients' 3-year EFS was 97.
4% and the 3-year OS rate was 98.
7%; while the historical control group patients were 80.
8% (P=0.
0008) and 96.
5% (P=0.
311).

The overall treatment tolerance of the patients in this trial was well tolerated.
Adverse events (AE) were mainly low-grade nausea, vomiting and constipation.

The most common AE is hematological toxicity, especially in the first 2 cycles of treatment.

Twelve patients (2.
6%) received red blood cell infusion during treatment, 19 patients (25%) received recombinant human granulocyte colony stimulating factor treatment; 8 patients (10%) were due to febrile neutropenia (FN ) Hospitalized. Seven patients (9%) confirmed the presence of clinical symptoms of osteonecrosis on imaging.

Neuropathic and non-neuropathic pain are less common, and the incidence of related grade 3 AEs is 4%.

Compared with patients in the historical control group, the patients receiving radiotherapy in this trial had an average cardiac dose of radiotherapy reduced from 16.
9 Gy to 5.
29 Gy (P<0.
001), and an average thyroid dose reduced from 25.
9 Gy to 4.
46 Gy (P<0.
001).

In addition, the breast exposure dose of the female population was significantly reduced.
The average breast dose of radiotherapy for the trial patients was 3.
21 Gy, compared with 6.
85 Gy for the historical control group (P=0.
004).

Research conclusions The results of this trial confirm that compared with previously published clinical trials for children with high-risk cHL, the AEPA-CAPDac regimen is well tolerated, helps reduce the dose of radiotherapy for children, and has better 3 years of EFS and OS.

A longer follow-up time is needed to further confirm the efficacy and safety of this program.

The good safety and tolerability of verbutuximab combined with chemotherapy in high-risk children with cHL supports its further prospective randomized trials.

References: Monika L Metzger, Michael P Link, Amy L Billett, et al.
Excellent Outcome for Pediatric Patients With High-Risk Hodgkin Lymphoma Treated With Brentuximab Vedotin and Risk-Adapted Residual Node Radiation.
J Clin Oncol.
2021 Apr 7;JCO2003286 .
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