 Home > Active Ingredient News > Blood System > Ji Chunyan and Professor Wang Xin | Season 2: How to grasp the timing of 1L DLBCL treatment? Verptozumab focuses on clinical and value needs, steadily improving the "happiness" of treatment-naïve patients

Ji Chunyan and Professor Wang Xin | Season 2: How to grasp the timing of 1L DLBCL treatment? Verptozumab focuses on clinical and value needs, steadily improving the "happiness" of treatment-naïve patients

 Last Update: 2023-02-03
 Source: Internet
 Author: User

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Guide

Every unknown world opens, there are pioneers bravely foreseeing; Every journey of night sneaking is accompanied by a lighter who fearlessly leads the way
.
The second season of the series "Solving the Problem - Unlocking the New Standard of DLBCL Cure" starts a new season, digging into the problems in the treatment of diffuse large B lymphoma (DLBCL) and exploring the unmet clinical needs; Combining clinical research, classic cases, and real-world treatment experience at home and abroad, we will jointly explore the new standard
of precision diagnosis and treatment of DLBCL.
Polatuzumab Vedotin (Pola) turned into Pole Star, under the guidance of field leaders, to help optimize diagnosis and treatment strategies, with the upcoming approval of vebutuzumab officially entered China, Chinese DLBCL patients are expected to further improve survival benefits
.

This issue is a topic

DLBCL is an aggressive disease and patients tend to have a high
burden of disease.
Immunochemotherapy regimens currently play an important role in the first-line (1L) treatment of DLBCL, but approximately 40% of patients still experience disease progression after treatment, and some patients, such as older patients, have limited benefit and poor survival outcomes
.
How to time 1L DLBCL treatment? Reducing the burden of disease and treatment costs for patients at an early stage?

Star solution expert

Qilu Hospital of Shandong University

Professor Ji Chunyan

Shandong Provincial Hospital

Professor Wang Xin

Patients with DLBCL have limited benefit from 1L chemotherapy, and the cost of subsequent treatment is significantly increased

, and patients with DLBCL do not survive well

DLBCL is an aggressive disease and is the most common type
of non-Hodgkin lymphoma.
CONCORD-3 data show that the 5-year overall survival (OS) rate of lymphoma patients in China between 2010 and 2014 was only 38.
3%¹, while DLBCL as a highly aggressive subtype may have worse survival
.

About 40% of patients progress after R-CHOP 1L treatment, and the benefit is limited in older patients

Historically, the R-CHOP regimen (rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone) was the "gold standard"
for DLBCL 1L therapy.
However, disease progression occurs in approximately 40% of patients after R-CHOP treatment, and 83% occur within
3 years of treatment.
Most patients have poor survival outcomes after disease progression (Figure 1), with 70% dying from lymphoma within the first 2 years after progression with a median OS of only 0.
7 ^months2
.

Fig.
1 Survival outcomes for DLBCL patients after disease progression

In addition, among patients with DLBCL, older patients often have limited benefit due to many comorbidities, poor chemotherapy tolerance, high degree of disease invasion, and high risk of recurrence.

Moreover, some elderly patients cannot tolerate the standard dose of R-CHOP regimen, which still poses great challenges
to the clinical management of such patients.

Treatment costs increase significantly after progression in patients with DLBCL

Retrospective cohort studies in the US showed a significant increase in disease costs following advances in DLBCL 1L therapy, particularly in patients receiving novel therapies in the later ^line3
.
The latest real-world study presented at the 2022 ASH Annual Meeting showed that the total cost of treatment for relapsed/refractory (R/R) DLBCL increased with the number of lines (Figure 2)⁴
.

Fig.
2 The total cost of treatment for DLBCL patients increases with the increase of the number of treatment lines

Given the patient's burden of disease and the cost of treatment, an early benefit from 1L DLBCL treatment may have a positive impact
on subsequent treatment outcomes.
Therefore, DLBCL requires new approaches to 1L treatment that are both effective and cost-effective
.

The Pola-R-CHP program comprehensively improves the benefits of patients and reduces the burden

of treatment, and the "magic bullet" innovative mechanism takes into account high efficiency and low toxicity

In order to combine the targeted selectivity of monoclonal antibodies with the high potency of cytotoxic drugs to overcome the limitations of traditional chemotherapy and targeted therapy, antibody conjugates (ADCs) are a novel therapeutic modality
.
ADCs are known as the "magic bullet" by targeting potent cytotoxic drugs to target cancer cells, providing a wider therapeutic window and limiting off-target ^effects5
.

As the world's first ADC approved for the treatment of DLBCL, vepotuzumab is one of the few drugs in past studies that has achieved a breakthrough in efficacy without increasing toxicity, which is inseparable from the innovative drug design of veptozumab (Figure 3).

。 CD79b antibody can enable vepotuzumab to accurately localize tumor cells; The lysing linker ensures stable delivery of MMAE to target cells and avoids "accidental injury" of normal cells; Free MMAE hinders tubulin polymerization, leads to apoptosis of tumor cells, and further kills surrounding tumor cells through bystander effect, thereby achieving efficient and low-toxicity therapeutic effects
.

Fig.
3 Drug structure of vepotuzumab

Clinical application value of Pola-R-CHP regimen: improve survival benefit

In the past 20 years, many researchers have explored the 1L treatment option for DLBCL, but all have failed
.
Until 2017, a randomized, double-blind, placebo-controlled international phase III study POLARIX study confirmed the clinical use
value of Pola-R-CHP (vepotuzumab + rituximab + cyclophosphamide + doxorubicin + prednisone).

The results of the study showed that Pola-R-CHP 1L treatment improved patient survival
compared with the R-CHOP regimen.
At a median follow-up of 28.
2 months, the 2-year progression-free survival (PFS) rate was 6.
5% higher in the Pola-R-CHP group than in the R-CHOP group (76.
7% vs 70.
2%) (Figure 4); The 2-year event-free survival (EFS) rate was 6.
2% higher (75.
6% versus 69.
4%) in the R-CHOP ^group6
.

FIGURE 4 POLARIX STUDY 2-YEAR PFS RATE

For older patients aged > 60 years, patients with molecular risk factors, and Asian patients, Pola-R-CHP showed a significant improvement in 2-year PFS rates compared with R-CHOP (Figure 5)⁶
.

FIG.
5 SUBGROUP ANALYSIS OF PFS RATE IN POLARIX STUDY FOR 2 YEARS

Clinical application value of Pola-R-CHP program: good safety

The results of the POLARIX study showed that the overall safety profile of the two groups was comparable, with a higher proportion of patients in the Pola-R-CHP group receiving a full course of therapy and fewer adverse events (AEs) leading to dose reduction (Figure 6)⁶
.

FIG.
6 OVERALL SAFETY ANALYSIS OF POLARIX RESEARCH

Clinical application value of Pola-R-CHP regimen: improving health-related quality of life

The results of the health-related quality of life (HRQoL) analysis of the POLARIX study, presented at the 2022 ASH Annual Meeting, showed that the Pola-R-CHP regimen improved lymphoma symptom scores in 82.
3% of patients after cycle 1 treatment and showed sustained improvement in the first evaluation after treatment ended (Figure 7)⁷
.

FIG.
7 POLARIX STUDY HRQoL ANALYSIS

Clinical application value of Pola-R-CHP program: reduce the treatment burden of patients

An interim analysis of the POLARIX study, presented at the 2022 ASH Annual Meeting, evaluated the potential impact of
Pola-R-CHP on second-line therapy.
Results showed a significant reduction in the proportion of patients receiving second-line therapy in the Pola-R-CHP group compared with R-CHOP (cumulative incidence of second-line therapy at 24 months: 17.
1% vs 24.
4%)
.
Pola-R-CHP is expected to reduce the risk of second-line therapy by 27% over 10 years (Figure 8), significantly reducing the burden of patients undergoing late-stage ^treatment8
.

FIGURE 8 THE POLARIX STUDY ESTIMATES THE NUMBER OF PATIENTS RECEIVING SECOND-LINE THERAPY FROM 2023 TO 2033

The above research data shows that Pola-R-CHP regimen brings all-round benefits to treatment-naïve DLBCL patients, especially in the early stage of treatment, reducing the treatment burden of patients, helping to improve patients' "happiness", and bringing new choices and new hopes
to the elderly and high-risk patient groups.

Star Interpretation Quotes:
Professor Ji Chunyan, Qilu Hospital of Shandong University

With the continuous emergence of new drugs such as immunotherapy and targeted therapy, there are more and more
treatment options for DLBCL.
However, for the first-line treatment of DLBCL, the R-CHOP regimen is always an insurmountable "high wall"
.
In the past two decades, the Pola-R-CHP regimen has become the first first-line therapy to surpass the classical R-CHOP regimen, and POLARIX research has therefore become epoch-making and
significant.
WITH THE EXTENSION OF FOLLOW-UP AND THE DEEPENING OF EXPLORATION, POLARIX RESEARCH BRINGS US MORE AND MORE SURPRISES, DLLBCL PATIENTS ARE EXPECTED TO ACHIEVE A FULL RANGE OF BENEFITS, AND A CURE MAY BE JUST AROUND THE
CORNER.

Shandong Provincial Hospital The emergence of new therapeutic drugs by Professor Wang Xin has brought a new
revolution in treatment, and in the era of precision medicine, we should further pursue mechanism-based treatment strategies to achieve the goal
of curing DLBCL 。 As an ADC with a unique mechanism of action, vepotuzumab combines the targeted selectivity of monoclonal antibodies with potent cytotoxicity, and its combination therapy regimen not only improves the efficacy of immunochemotherapy, but also maintains good safety characteristics, and also shows benefits in improving the quality of life of patients and reducing the burden of treatment, which is expected to improve the survival outcomes
of patients with treatment-naïve DLBCL in the early stage of treatment.

Professor Ji Chunyan

Famous teacher of Shandong University and distinguished professor of outstanding talent system
Deputy Dean of Qilu Medical College of Shandong University
Vice President of Qilu Hospital of Shandong University and Director of Cancer Center
Director of the Joint Laboratory of Intelligent Diagnosis and Treatment of Hematological Diseases, Shandong University
Taishan Scholar climbing plan expert
Young and middle-aged experts with outstanding contributions to national health and family planning
Enjoy the special government allowance of the State Council
Outstanding discipline leader of health system in Shandong Province
Chairman of the Hematological Oncology Professional Committee of the Chinese Anti-Cancer Association
Vice Chairman of Hematology Branch of Chinese Hospital Association
Member of Hematology Branch of Chinese Medical Association
Chairman of Hematology Branch of Shandong Medical Association
Chairman-elect of Hematological Oncology Branch of Shandong Anti-Cancer Association
Chairman-elect of Clinical Analysis Cell Branch of Shandong Medical Association

Professor Wang Xin

Director of Cancer Center, Director of Hematology Department and Doctoral Supervisor of Shandong Provincial Hospital
Dean of Clinical Medical College of Shandong University, expert in outstanding talent system, second-level professor
Taishan Scholar Climbing Program Distinguished Professor
Special expert of the State Council for special allowances
Chairman of the Hematology Cancer Translational Medicine Branch of the Chinese Anti-Cancer Association
Member of the Teaching Steering Committee of Clinical Medicine in Colleges and Universities of the Ministry of Education
Standing Committee Member of Hematology Branch of Chinese Medical Doctor Association
Member of Hematology Branch of Chinese Medical Association
Chairman of the Diagnostic Branch of Shandong Medical Association
Chairman of Hematology Branch of Shandong Medical Doctor Association
Chairman of the Stem Cell and Cell Application Translational Medicine Special Committee of Shandong Medical Doctor Association
Chairman of the Anti-lymphoma Special Committee of Shandong Clinical Oncology Society
ASH member of the American Blood Association

References

[1] Allemani C, et al.
Lancet.
2018 Mar 17; 391(10125):1023-1075.

[2] Coiffier B, et al.
Blood.
2010; 116(12):2040-2045.

[3] Rongrong Wang, et al.
ASH2021 P-3002.

[4] Justin Gatwood, et al.
ASH2022 P-3527.

[5] Jabbour E, et al.
Nat Rev Clin Oncol.
2021; 18(7):418-433.

[6] Tilly H, et al.
N.
Engl.
J.
Med 2021 Dec 14.

[7] Jonathan W.
Friedberg, et al.
ASH2022 P-2949.

[8] Frédéric Boissard, et al.
ASH2022 P-2958.

Past Review

Puzzle Star Solution | Professor Zhao Weiying and Professor Liu Yanyan: How to break through the R/R DLLCL problem? Chinese and foreign experience unlocks new solutions

Professor Zhu Jun and Professor Guo Ye: Pola's three major offensive tools (1) - MMAE bystander effect lays the mechanism foundation for breaking through the heterogeneity of DLBCL

Puzzle Star Solution | Professor Ma Jun: The more classic the effect, the more the stage of healing, 1L DLBCL treatment is ushering in a new standard

Puzzle Star Solution | Professor Zhang Huilai and Professor Tao Rong: Pola's three major offensive weapons (2) - CD79b innovative target accurate breakthrough, DLBCL's world's first "magic bullet" leads the new channel

Puzzle Star Solution | Professor Huang Huiqiang: Pola helps patients with non-transplantable R/R DLBCL rekindle hope

Puzzle Star Solution | Professor Wu Depei and Zhang Xi: Relay together, continue hope, innovative ADC drug Pola opens up a new pattern suitable for transplantation of R/R DLBCL treatment

Puzzle Star Solution | Professor Zhang Qingyuan: Pola's three major attack tools (3) - cleavage linker, the guarantee of "strong and low toxicity" of ADC drugs

Professor Feng Jifeng and Professor Qiu Lugui: Turning the tide, Pola provides guidance for repeated progress in DLBCL

Professor Zhou Daobin and Professor Li Zhiming: Pola brings new treatment options for elderly frail/intolerant patients with DLBCL

Song Yongping and Professor Zhang Wei: Bravely climb the peak, innovate ADC drug Pola-enabled transplantation and CAR-T treatment, and explore more therapeutic potential

Professor Niu Ting and Professor He Pengcheng: Through the fog, the innovative ADC drug Pola continues hope for patients with failed CAR-T treatment DLBCL

Jin Jie and Professor Li Jianyong: Pola may become the best choice for the future treatment of first-line high-risk DLBCL patients

Puzzle Star Solution | Professor Song Yuqin and Professor Georg Lenz: The innovative ADC drug Pola strikes accurately, breaks through the bottleneck of DLBCL first-line treatment, and writes a new starting point for treatment

Editor: Moon Reviewed: Janet Typesetting: Moly Execution: Moly

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