2021 ICML A+AVD program for the treatment of adolescents and young adults cHL

Classical Hodgkin’s lymphoma (cHL) has a low incidence and is common in adolescents and young adults (AYA)
.

The patient was young at the time of treatment, so the choice of treatment should not only increase the cure rate, but also reduce long-term toxicity
.

Verbutuximab (BV) is an antibody-drug conjugate (ADC) that targets CD30.
The 5-year follow-up results of the Phase III ECHELON-1 study showed that it is compatible with doxorubicin, bleomycin, and Changchun Compared with the base and dacarbazine (ABVD) regimen, the BV combined with doxorubicin, vinblastine and dacarbazine (A+AVD) regimen significantly improved the patient’s progression-free survival (PFS; HR: 0.
69; 95% CI) : 0.
54-0.
9; P=0.
003)
.

The open-label Phase I/II C25004 study also evaluated the safety and efficacy of the first-line A+AVD regimen in pediatric patients with advanced cHL
.

The key efficacy and safety results of AYA patients in the ECHELON-1 study and the results of the C25004 study were announced at this year's ICML conference
.

The editor organizes the main contents of the two studies as follows for the reference of readers
.

Abstract No.
: 038 Title: Verbutuximab combined with chemotherapy in the treatment of stage III/IV Hodgkin's lymphoma AYA patients: subgroup analysis of the phase 3 ECHELON-1 study 1 research method ECHELON-1 study (n=1334) Yes A global, open-label, multi-center, randomized study of newly treated stage III/IV cHL patients
.

A total of 771 AYA patients (58%) underwent PET examination (PET2) after 2 cycles of A+AVD (n=396) or ABVD (n=375) treatment
.

2 Study results After a median follow-up of 60.
7 months (95%CI: 60.
4-61.
0), the A+AVD group had a 36% lower risk of progression or death compared with the ABVD group (HR: 0.
64; 95%CI: 0.
45-0.
92; P=0.
013), the 5-year PFS rates were 86.
3% and 79.
4%, which were similar to those in the intention-to-treat (ITT) population
.

The PFS benefit of the two groups of patients was independent of PET2 status, and the rates of PET2 positive (Deauville score 4-5) were 6% and 8%, respectively
.

There were 81 patients (20%) and 96 patients (26%) in the A+AVD group and the ABVD group who received at least one follow-up treatment (including radiotherapy), respectively, 26 patients (7%) and 32 patients ( 9%) received high-dose chemotherapy and autologous hematopoietic stem cell transplantation
.

Peripheral neuropathy (PN) occurred in 64% and 40% of patients in the A+AVD group and ABVD group, respectively.
88%-89% of the patients in both groups had PN regression or improvement.
The persistent PN was mainly grade 1 ( 62%) and grade 2 (26%), 8 patients and 1 patient had persistent grade 3 PN, respectively
.

In the A+AVD and ABVD groups, 7 patients (1.
8%) and 5 patients (1.
4%) developed secondary malignancies, respectively
.

The partners of 44 patients in the A+AVD group and 26 female patients in the ABVD group, 31 patients in the A+AVD group and 30 male patients in the ABVD group became pregnant after treatment, and there was no report of stillbirth
.

3 The conclusions of the study are consistent with the results of the ITT population.
Compared with the ABVD regimen, the A+AVD regimen has long-lasting PFS benefits in the treatment of AYA patients, and most PN events can be improved or subsided
.

The A+AVD regimen can be a treatment option for AYA patients with stage III/IV cHL
.

Abstract No.
: 037 Title: Open-label Phase I/II study of A+AVD regimen in the treatment of pediatric patients with advanced Hodgkin’s lymphoma.
1 Study method: age 5-18 years, Lansky/Karnofsky performance status (LKPS) score ≥50, with Newly treated stage III/IV cHL patients with two-dimensional measurable disease met the inclusion criteria
.

In the phase I study, patients receive up to 6 cycles of A+AVD regimen treatment (administered on the 1st and 15th day of each cycle, the dose of BV is 36mg/m2 or 48mg/m2; 28 days is a treatment Period)
.

The main purpose is to evaluate safety, tolerability, and determine the phase II recommended dose (RP2D) for BV
.

In the phase II study, the main purpose is to evaluate the objective response rate (ORR: complete response [CR] + partial response [PR] rate), PET negative after 2 cycles of treatment (PET2-: Deauville score of 1-3 points) Rate, and the proportion of patients who completed 6 treatment cycles with RP2D
.

The secondary purpose is to evaluate the proportion of patients receiving radiotherapy after study drug treatment, and the safety and tolerability of the A+AVD regimen
.

2 The results of the study included 59 patients (Phase I study: n=8, Phase II study: n=51), the median age was 14 (range 6-17) years, 53% were male, and the median LKPS score was 90 (Range 70-100)
.

RP2D is 48mg/m2
.

All patients received 6 cycles of A+AVD treatment
.

At the end of treatment, the ORR assessed by the independent review agency was 88% (95% CI: 77, 95), and 76% of the patients (95 CI: 63, 86) achieved CR
.

The PET2-rate is 90% (95%CI: 79,96)
.

After a median follow-up of 17.
31 months, 13 patients (22%) had disease progression
.

The most common "treatment period" adverse events (TEAE) of any grade were vomiting (85%), nausea (75%), and neutropenia (58%); 41% of patients had serious AEs (SAE)
.

There were no deaths in the study
.

3 Research conclusions For pediatric patients with advanced cHL, the first-line BV (48mg/m2) combined with AVD regimen is well tolerated, and has high ORR, CR rate and PET2-rate, which is in line with the adult efficacy and safety observed in the ECHELON-1 study Unanimous
.

The study will continue to follow up patients
.

Reference source: 1.
HE Crosswell, et al.
2021 ICML.
038.
2.
ARK Franklin, et al.
2021 ICML.
037.
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