Verbutuximab is used as a single agent to treat R/R cHL, and new evidence-based evidence has been released!

Introduction Regarding "Vibtuximab in the treatment of relapsed or refractory classic Hodgkin's lymphoma", evidence of systematic review meta-analysis is released! Hodgkin’s lymphoma (HL) is a malignant disease of the lymphatic system characterized by the presence of Reed-Sternberg (RS) cells [1].
It is divided into two major types: classic and nodular lymphocytes.
The classic Hodgkin's lymphoma (cHL) accounts for about 90% [2]
.

With the application of modern therapy and radiotherapy, HL has become one of the most curable malignant tumors, but there are still 10%~15% of early-stage patients and 20%~30% of late-stage patients will relapse after initial treatment [1 ]
.

For patients with relapsed or refractory (R/R) cHL, only half of them can achieve long-term complete remission (CR) through high-dose chemotherapy and autologous stem cell transplantation (ASCT), which means that there is a field of R/R cHL treatment Important, unmet medical needs [1]
.

Verbutuximab (BV) for injection is an anti-CD30 antibody-conjugated drug, which has been confirmed by multiple studies to be effective and well tolerated in the treatment of R/R cHL
.

A recently published systematic review and meta-analysis used real-world data obtained from observational studies to update the evidence for the treatment of BV in cHL [1]
.

System review search results: A total of 32 observational studies were included.
A total of 32 reports were included in the system review to report treatment mode, overall response rate (ORR), CR rate, progression-free survival (PFS), overall survival (OS), and observational properties of adverse events The study (Table 1) contains data on the effectiveness or safety of BV in the treatment of R/R cHL in the real world environment for more than ten years (1996-2019)
.

Table 1 Features of the included studies in the systematic review (N=32) The studies included a total of 2303 patients, and the patient population among the studies was relatively homogeneous; the median age was between 27 and 45.
7 years old, most of the studies included Most patients had received ASCT before starting BV treatment, and a few reported that most of the patients included in the study had an ECOG score of ≤2
.

1.
The combined ORR of curative effect treatment for more than 6 cycles was 72.
0%, and the CR rate was 33.
4%.
Based on the results of 24 studies, the ORR range of BV for R/R cHL was 46.
6%~84.
0%
.

The 4 case series reported low ORR estimates (20.
6%~40.
0%), which may be related to the characteristics of the study population, that is, they have received severe pretreatment, are ineffective in previous salvage treatments, or are due to the persistence of the disease.
Not suitable for ASCT related
.

Based on the results of 22 studies, the CR rate ranged from 21.
1% to 45.
8%
.

In the 4 case studies, the CR rate was estimated to be low (14.
3%~16.
7%), which may be related to the small sample size (n=21, n=24, n=18) or patient characteristics, that is, receiving 4 kinds of medium It is related to patients who have been heavily pretreated by previous programs and have failed to respond to previous rescue treatments
.

Of the 26 studies that reported ORR or CR estimates, 12 were published in full text for meta-analysis
.

The results showed that the combined ORR and CR rates after 4 cycles of BV treatment were 62.
6% and 32.
9%, respectively, 66.
7% and 32.
4% after 4 to 6 cycles, and 72.
0% and 33.
4% after more than 6 cycles ( Figure 1 and Figure 2)
.

Regardless of whether it is ORR or CR, estimates from good and medium-quality studies and including studies published as abstracts are similar to the results of the above meta-analysis, which confirms the robustness of the results
.

In addition, as shown in the funnel plots (Figure 1D and Figure 2D), the distribution of studies around the average estimate is relatively symmetric, which indicates that there is no or only slight publication bias
.

Figure 1 Meta analysis of total response rate
.

(A) Forest plot of estimated ORR values ​​after 4 cycles of BV treatment (first subgroup); (B) Forest plot of estimated ORR values ​​after 4-6 cycles of BV treatment (second subgroup); (C) BV Forest plot of ORR estimates after treatment for ≥6 cycles (third subgroup); (D) Funnel plot of full-text published studies reporting ORR estimates (n=12) Figure 2 Meta-analysis of complete remission rate
.

(A) Forest plot of estimated CR rate after 4 cycles of BV treatment (first subgroup); (B) Forest plot of estimated CR rate after 4-6 cycles of BV treatment (second subgroup); (C ) Forest plot of the estimated CR rate after 6 cycles of BV treatment (subgroup 3); (D) Funnel plot of the full-text published study reporting the estimated CR rate (n=12) Researcher’s interpretation: This meta-analysis shows that, The combined ORR and CR rates after BV treatment for more than 6 cycles were 72.
0% and 33.
4%, respectively, which were similar to the ORR (75%) and CR rates (34%) reported in the pivotal phase II trial [3]
.

However, compared with the key phase II trial (patients with ECOG PS scores limited to 0 or 1, and no allogeneic SCT) [3], some patients in the observational studies included in this meta-analysis have a worse prognosis (ie ECOG PS score) 2 or higher, or failure of allogeneic SCT, or not suitable for transplantation)
.

This shows that for patients receiving BV treatment in a real-world clinical practice environment, even if the subgroup of patients with a worse prognosis is included, the efficacy (ORR, CR estimate) is consistent with the results reported in the key trial
.

2.
The 5-year survival rate of PFS was 31.
9%~33.
0%, and the 5-year OS rate was 58.
0%~62.
0%.
18 studies reported PFS data, of which 12 (66.
7%) reported median PFS ranging from 5 to 16.
6 months
.

Eighteen studies reported OS estimates, five of which reported median OS: 17.
8, 26.
5, 33.
2, 57.
0, and 91.
5 months
.

Based on the research that reports the PFS rate and OS rate, the 1-year PFS rate is: 52.
1%, 63.
2% (from 2 studies); the 2-year PFS rate is: 45.
2%, 51%, 56.
2% (from 3 studies); 3 The annual PFS rate is: 36.
7% (from 1 study); the 5-year PFS rate is: 31.
9%, 33.
0% (from 2 studies)
.

The 1-year, 2-year, 3-year, 5-year and 10-year OS rates ranged from 68.
2% to 82.
7% (from 6 studies), 58.
0% to 81.
9% (from 7 studies), 41% to 74.
6% (from 2 studies), 58.
0%~62.
0% (from 3 studies) and 33% (from 1 study)
.

The PFS meta-analysis was not performed due to lack of information about the data distribution; in addition, the OS meta-analysis was not performed because the studies considered to be of good methodological quality used different OS definitions
.

Researcher's interpretation: Although the meta-analysis was not performed, the overall PFS and OS data are consistent with the key phase II trial data; the 5-year long-term follow-up data of the key phase II trial showed that the median OS and PFS were 40.
5 months and 40.
5 months, respectively.
For 9.
3 months, the estimated 5-year OS rate and PFS rate were 41% and 22%, respectively [4]
.

This shows that in a real-world clinical practice environment, the estimated values ​​of PFS and OS for BV treatment are consistent with the results reported in key trials
.

3.
Safety Most PN events are grade 1 or 2.
Based on 12 reported safety studies, the most common BV-related adverse events are neutropenia, anemia, and thrombocytopenia
.

Regarding peripheral neuropathy (PN), 11 studies found that most were grade 1 or 2 (36.
2%), and only a few were grade 3 or above (3.
3%~7.
3%); one of the studies indicated that the vast majority ( 90%) The PN symptoms of patients subsided or improved at 12 weeks
.

Researcher's interpretation: The above data are consistent with the results of the key phase II trial
.

The key phase II trial showed that the incidence of PN for BV treatment was 55%, and most events were Grade 1 or 2; among PN patients, 88% of patients had symptoms that completely resolved or improved [3,4]
.

Conclusion The observational studies included in this systematic review and meta-analysis include a wider and more heterogeneous population, and the displayed ORR, CR, PFS, and OS estimates are consistent with the key Phase II trial results, as are the safety results
.

This provides new high-level evidence for the clinical use of BV to treat R/R cHL
.

References[1]Plattel WJ, Bergamasco A, Trinchese F, et al.
Effectiveness of brentuximab vedotin monotherapy in relapsed or refractory Hodgkin lymphoma: a systematic review and meta-analysis[J].
Leuk Lymphoma.
Published online: 29 Jul 2021.
[2] Chinese lymphoma treatment guidelines (2021 edition).
[3] Younes A, Gopal AK, Smith SE, et al.
Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma[J].
J Clin Oncol.
2012 Jun 20;30(18):2183-9.
[4]Chen R, Gopal AK, Smith SE, et al.
Five-year Survival and Durability Results of Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma [J].
Blood.
2016 Sep 22;128(12):1562-6.
Material approval number: VV-MEDMAT-57220 Material approval date: 11/2021 statement This information is intended to help medical and health professionals better understand the relevant The latest developments in the field of diseases
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