Introduction
Based on Western population data, Verbutuximab (BV) for injection will be approved for marketing in China in 2020. So, what is the therapeutic effect of BV for Chinese patients?
In China, treatment options for relapsed or refractory (R/R) classic Hodgkin’s lymphoma (cHL) and R/R systemic anaplastic large cell lymphoma (sALCL) are limited, so there is an urgent need New therapy.
BV is an antibody-conjugated drug (ADC) targeting CD30. It has been approved in China for the treatment of CD30-positive R/R sALCL and cHL adult patients, and has been included in Chinese Society of Clinical Oncology ( CSCO) recommended medication [1] in the guidelines. The approval of
BV is mainly based on clinical studies conducted in western patient populations (SG035-0003, SG035-0004, C25007) [2] . So, what is the therapeutic effect of BV in Chinese patients? Recently, the data of "Chinese registration study of BV treatment of CD30+ R/R cHL or sALCL patients" published [1] .
China registration study: Verbutuximab is effective, safe and feasible
This is a single-arm, open-label, multi-center, phase II study conducted in 7 medical centers in mainland China, evaluation The efficacy, safety and pharmacokinetic (PK) characteristics of BV monotherapy in Chinese patients with R/R cHL and R/R sALCL are reviewed.
study enrolled patients ≥18 years old, with measurable lesions, histology examination confirmed as CD30+ cHL or sALCL, disease recurrence after previous treatment or ineffective (refractory) to previous treatment, BV (1.8 mg/ kg IV,Q3W) Treatment is up to 16 cycles, or until the disease progresses, toxicity is unacceptable, subsequent stem cell transplantation (SCT) is started, or informed consent is withdrawn [1] .
The primary endpoint is the overall response rate (ORR) and safety as assessed by the investigator. Secondary endpoints include additional efficacy indicators [complete remission (CR) rate, duration of remission (DOR), progression-free survival (PFS), overall survival (OS)], rate of B symptom resolution, PK characteristics, and immunogenicity.
results showed that all included patients had measurable lesions at baseline and received ≥1 dose of BV treatment (39 cases, including 30 cases of R/R cHL and 9 cases of R/R sALCL), that is, the modified intention-to-treat (mITT) population Consistent with the safety assessment population.
As shown in Table 1, at the beginning of the study, most patients had advanced disease and had received up to 7 previous treatments (including bone marrow transplantation or SCT). This not only reflects the clinical characteristics of patients diagnosed with R/R cHL and R/R sALCL in China, but also reflects the current clinical practice in China.
Table 1 Baseline characteristics of safety/mITT population
1. Efficacy
ORR was 69%, median DOR was 12.1 months, median PFS was 13.5 months, median OS did not reach
BV treatment showed good anti-tumor activity:
-
mITT population had a ORR of 69% and a CR rate of 28%. The ORR of the cHL subgroup was 70%, and the CR rate was 20%. The ORR of the sALCL subgroup was 67%, and the CR rate was 56% (Table 2).
-
In the mITT population,92% of patients achieved tumor shrinkage (97% in the cHL subgroup and 78% in the sALCL subgroup; Figure 1). Sixteen patients (41%) achieved remission within 2 months after the first dose of BV treatment, 7 patients (18%) experienced progressive disease remission during treatment, and 5 patients (13%) received follow-up ASCT (3 cases of cHL, 2 cases of sALCL).
-
In the mITT population, the median DOR of patients with CR or PR was 12.1 months . At a DOR of 12 months, the ORR of the cHL subgroup was 42% (Figure 2A) and the ORR of the sALCL subgroup was 83% (Figure 2B). The median PFS of the
-
mITT population was 13.5 months . At 12 months, the K-M method for the mITT population estimated a PFS rate of 52%, 49% for the cHL subgroup (Figure 2C), and 56% for the sALCL subgroup (Figure 2D).
-
At a median OS follow-up of 16.6 months, the median OS of the mITT population did not reach. At 12 months, the K-M method for the mITT population estimated the OS rate of 85%, 90% for the cHL subgroup (Figure 2E), and 65% for the sALCL subgroup (Figure 2F).
These assessment results are consistent with the key research findings approved by BV for R/R cHL and R/R sALCL. The clinical effectiveness of BV in Chinese patients makes it possible for patients to "bridge" SCT and ultimately achieve cure.
Table 2 The best remission of mITT population
CR, complete remission; DCR, disease control rate; cHL, classic Hodgkin's lymphoma; mITT,Modified intention to treat; ORR, total response rate; PD, disease progression; PR, partial response; sALCL, systemic anaplastic large cell lymphoma; SD, stable disease
Figure 1 (A) cHL and (B) sALCL The waterfall chart of the subgroup counts the best percentage change of the sum of diameter products. CR, complete remission; cHL, classic Hodgkin's lymphoma; mITT, modified intention-to-treat; PD, disease progression; PR, partial remission; sALCL, systemic anaplastic large cell lymphoma; SD, stable disease; SPD, vertical Sum of diameter products
Figure 2 Kaplan-Meier curves of cHL (left) and sALCL (right) subgroups. (A) and (B) show the duration of remission. (C) and (D) show progression-free survival. (E) and (F) show overall survival. cHL: classic Hodgkin's lymphoma; CR: complete remission; mITT: modified intention-to-treat; NE: inestimable; ORR: total response rate; ALCL: anaplastic large cell lymphoma
2. Safety
Patients are well tolerated, and adverse events are usually controllable and reversible
In the safety/mITT population, patients received the approved dose of BV for R/R cHL and sALCL, with a median treatment cycle of 10 During the period, the median relative dose intensity (RDI) was 98%, indicates that most patients received the required dose intensity.
38 patients (97%) had ≥1 time of any grade of drug-related adverse events (TEAE) during treatment, most of which were grade 1-2, and 10 cases (26%) were grade ≥3 (Table 3 ).
Table 3 Summary of Adverse Events (AE)
† Drug adjustment refers to dose reduction, dose increase, dosing delay or withdrawal
The most common TEAEs are hematological toxicity/abnormality, blood biochemical abnormality and Peripheral neuropathy,However, these events are usually controllable and reversible:
-
Hematological abnormalities: at the end of treatment (EOT), all neutropenia cases, most leukopenia and anemia cases hematological abnormalities Has been restored.
-
Abnormal blood biochemistry: In the absence of clinical intervention (stopping the drug or adjusting the dose), most alanine aminotransferase or aspartate aminotransferase can be restored.
-
Neuropathy: At the last EOT, 55% of the peripheral neuropathy (PN) events that occurred during the treatment period had resolved (Table 4).
During the study period, no patients died and no new safety signals were found.
The results show that BV treatment of Chinese R/R cHL or sALCL patients has acceptable safety and a good benefit-risk ratio, and its safety characteristics in the Chinese patient population are similar to those previously reported in the Western population.
In addition, the PK characteristics of ADC, total antibodies (TAb; ADC and CD30 targeted antibodies) and anti-microtubule drug monomethyl auristatin E (MMAE) observed in this study are similar to those of previous Western patients The same as described in the crowd.
Conclusion
For Chinese patients with R/RcHL and sALCL, BV has significant efficacy and controllable safety, and is an effective potential treatment option. I believe that in future clinical practice, more Chinese lymphoma patients who are suitable for BV will benefit from it.
References
[1] Song Y, Guo Y, Huang H, et al. Phase II single-arm study of brentuximab vedotin in Chinese patients with relapsed/refractory classical Hodgkin lymphoma or systemic anaplastic large cell lymphoma[J] Expert Rev Hematol. Accepted author version posted online: 2021 Jul 19.
[2] Instructions for Verbutuximab for Injection (Revision Date: April 13, 2021)
Material approval number: VV-MEDMAT- 51511
Material approval date: 8/2021
Statement
This information is designed to help medical and health professionals better understand the latest developments in the field of related diseases.The content of the information published by this site does not mean that it agrees with its description and opinions, but only provides more information. If copyright issues are involved, please contact us, and we will deal with it as soon as possible.
is only for medical and health professionals to understand information. Such information cannot replace professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice. If such information is used for purposes other than understanding the information, this site and the author shall not bear related responsibilities.
.-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-