Professor Zhang Mingming: Advances in Treatment of Peripheral T-Cell Lymphoma 2021 China Oncology Congress

Introduction Peripheral T-cell lymphomas (PTCLs) are a group of malignant proliferative diseases derived from mature T cells
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It is common in adults, often involving various tissues and organs of the body, with strong heterogeneity, poor prognosis, and easy recurrence
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CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) is commonly used in the treatment of PTCL, but the efficacy is poor, and it is not suitable for the first-line treatment of PTCL
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At the 2021 China Conference on Oncology (CCO) held online from April 14 to 17, 2022, Professor Zhang Mingming from the First Affiliated Hospital of Zhengzhou University summarized and shared the progress of PTCL treatment.
The editor organized the main contents as follows for readers' reference
.

The main types of PTCL and the main clinical features The main types of PTCL are peripheral T-cell lymphoma not specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), ALK positive/negative anaplastic large cell lymphoma (ALCL), enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliophilic intestinal T-cell lymphoma (METTL), peripheral lymph node T-cell lymphoma with TFH phenotype (PTCL-TFH), and follicular type T-cell lymphoma (FTCL)
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 Next, Professor Zhang Mingming introduced the main clinical features of PTCL-NOS
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The incidence of PTCL-NOS is mainly seen in adults, with a male to female ratio of about 2:1; it usually involves various tissues and organs in the body, including lymph nodes (50%-75%), of which retroperitoneal lymph nodes are more likely to be involved than mediastinal lymph nodes, and skin and subcutaneous tissue account for 20%.
%-50%, hepatosplenomegaly 5%-30%, bone marrow infiltration 25%-35%; CNS involvement is rare; group B symptoms are common (50%-60%); Relapse 2-3 years after treatment
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Professor Zhang Mingming mentioned that in the past, the CHOP regimen for the treatment of diffuse large B-cell lymphoma was often used to treat PTCL, but the efficacy was poor, with poor overall survival (OS) and progression-free survival (PFS).
ideal
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So how do other chemotherapy regimens work? Next, Professor Zhang Mingming introduced the efficacy of other regimens based on the CHOP regimen
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In the VACPE regimen, the investigators added etoposide to the CHOP regimen, and related research results showed that cutaneous T-cell lymphoma (CTCL), mycosis fungoides, lymphoblastic lymphoma, and HTLV-1-related T cells were excluded.
For cell lymphoma, the complete remission (CR) rate in PTCL patients after CHOP+etoposide regimen treatment can reach 77%, which significantly improves the event-free survival (EFS), but the OS does not significantly improve
.

CycloBEAP program adds etoposide and bleomycin on the basis of CHOP program, and the frequency of medication increases.
Related research results show that after the application of CycloBEAP program, the 5-year OS rate of PTCL (ALCL, ALT, PTCL-NOS) patients reaches 72% , 5-year PFS rate of 61%
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Studies have shown that after bortezomib monotherapy, the condition of CTCL patients is significantly relieved
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The results of a multi-center single-arm study showed that after bortezomib combined with CHOP treatment, the overall response rate (ORR) of PTCL patients was 76%, of which the ORR of PTCL-NOS and AITL patients was more than 80%, and the ORR of ALCL and CTCL patients was above 80%.
The ORR was 40% in patients with extranodal NK/T-cell lymphoma and 0% in patients with hepatosplenic T-cell lymphoma
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In addition, a number of studies have shown that gemcitabine has a good effect in the treatment of PTCL (the ORR of monotherapy can reach more than 50%, and the ORR of combination therapy can reach more than 60%)
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Professor Zhang Mingming's team conducted a randomized controlled clinical study in 2017.
The results showed that the GDPT regimen (gemcitabine, cisplatin, prednisone, thalidomide) can significantly improve the PFS of PTCL patients compared with the CHOP regimen.
and OS
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Targeted therapy for PTCL Prof.
Mingming Zhang then introduced the efficacy of targeted therapy in PTCL
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Monoclonal antibodies commonly used in the treatment of PTCL include anti-CD52 monoclonal antibody (Alemtuzumab), anti-CD30 monoclonal antibody (Velbutuximab [BV]), and anti-CCR4 monoclonal antibody
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Some studies have explored the efficacy of CHOP + Alemtuzumab in the first-line treatment of PTCL, and related research results show that the ORR after CHOP + Alemtuzumab treatment can reach more than 70%
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Another phase 1b/2 trial analyzed the efficacy of the Ro-CHOP regimen (CHOP + romidepsin + rituximab) in patients with PTCL.
The results of the study showed that after the application of the Ro-CHOP regimen, all patients CR was achieved after 6 cycles of treatment
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 In addition, some studies have analyzed the efficacy of BV in patients with relapsed and refractory systemic anaplastic large cell lymphoma (sALCL) after ≥1 treatment.
The results showed that BV monotherapy can achieve ORR of 86% in patients with sALCL.
, the CR rate reached 57%
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From the research results, BV can achieve better curative effect only with single drug treatment
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So if BV is used in combination with other schemes, will it also achieve ideal results? The ECHELON-2 study analyzed the efficacy of BV+CHP regimens (cyclophosphamide, doxorubicin, prednisone) and CHOP regimens in patients with PTCL.
The 5-year follow-up results showed that the patients who applied the BV+CHP regimen were significantly better than those who received the BV+CHP regimen.
Compared with CHOP patients, the PFS and OS benefits were significant, reducing the risk of disease progression by 30% and the risk of death by 28%
.

Prof.
Mingming Zhang specifically mentioned the regimen of BV+CHEP (CHP+etoposide) followed by autologous hematopoietic stem cell transplantation (Auto-HSCT) and BV consolidation therapy.
A phase II trial was used in patients with newly diagnosed CD30-expressing PTCL.
This program, the results of the study showed that the patients who applied this program had an ORR of 95% and a CR rate of 90%
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 Subsequently, Professor Zhang Mingming introduced other targeted drugs (Tipifarnib, lenalidomide and crizotinib) used in the treatment of PTCL
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Tipifarnib is a potent and highly selective FTase inhibitor for the treatment of AITL
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Not only that, a study showed that the ORR of Tipifarnib in patients with relapsed/refractory (R/R) AITL was 50%, and the study also found that the antitumor activity of Tipifarnib in R/R AITL was closely related to the KIR3DL2 gene mutation
.

A study of lenalidomide monotherapy in R/RT cell lymphoma showed that patients with lenalidomide monotherapy had an ORR of 30%
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In addition, Italian scholars reported 10 cases of lenalidomide in the treatment of R/R PTCL, and the results showed that 3 patients could achieve CR after lenalidomide monotherapy
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Another related study of the targeted drug crizotinib showed that crizotinib alone was used to treat refractory ALK-positive ALCL, and the CR rate could reach 82%
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 Professor Zhang Mingming reminded that special attention should be paid to the use of PD-1 in the treatment of PTCL.
It is prone to hyperprogression of the disease when used alone, and it is best to use it in combination with other drugs
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Currently, trials of PD-1 combined with PI3K inhibitors are ongoing
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In addition, the results of a study on CD5 CAR-T cell therapy for T-cell lymphoma showed that in 9 patients with CD5+ T-cell lymphoma (4 with T-cell acute lymphoblastic leukemia, 5 with T-cell non-Hodgkin's lymphoma) ), the total number of remissions was 4, of which 3 were in complete remission
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PTCL Hematopoietic Stem Cell Transplantation (HSCT) Next, Professor Zhang Mingming introduced the application of HSCT in PTCL
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The 5-year PFS rate of first-line Auto-HSCT for PTCL was 42%, and the 5-year OS rate was 47%
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Overall survival was improved in patients who received HSCT compared to those who did not
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In addition, the 5-year PFS rate was 50% and the 5-year OS rate was 61% in patients with PTCL who underwent allogeneic HSCT with reduced preconditioning intensity
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Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in the treatment of T-NHL, the 5-year PFS rate was 44%, and the 5-year OS rate was 51%
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Another study compared the efficacy of first-line Allo-HSCT and Auto-HSCT as consolidation therapy in patients with naïve PTCL.
The results showed that the survival rate of young PTCL patients receiving Allo-HSCT or Auto-HSCT after standard chemotherapy was similar, but due to the exclusion of Allo-HSCT Allopathic reaction, Auto-HSCT is still the preferred regimen for transplantable patients, and Allo-HSCT is an optional treatment regimen for relapse after Auto-HSCT
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Prognosis Among the subtypes of PTCL, the best prognosis is ALCL, and the worst prognosis is adult T-cell leukemia/lymphoma
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Patients aged >70 years with CD56 expression had a worse prognosis
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In addition, some studies have shown that different PTCL subtypes have different DNMT3A mutation profiles, and the combined DNMT3A mutation has a poor prognosis for patients with PTCL-TBX21 subtype
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Summary Professor Zhang Mingming finally concluded that PTCL is highly heterogeneous and the efficacy of CHOP regimen is limited
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Therefore, many scholars have explored the application of new drugs and new regimens in the treatment of PTCL
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For patients with ALK-positive PTCL, CD30 mAb + CHP is the first choice
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In the second-line treatment of PTCL, the combination regimen containing etoposide, gemcitabine, and lenalidomide has better efficacy
.

At the same time, some new drugs (CD30 monoclonal antibody, CAR-T, etc.
) also show good application prospects
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In addition, for patients who are suitable for transplantation, Professor Zhang Mingming suggested that Auto-HSCT should be used to consolidate the curative effect after first-line remission, and Allo-HSCT should be used for salvage treatment
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Expert Profile Professor Zhang Mingming, doctoral supervisor, director of the Oncology Center of the First Affiliated Hospital of Zhengzhou University, member of the Standing Committee of the Oncology Branch of the Chinese Medical Association, leader of the Translational Medicine Professional Group of the Chinese Medical Association Oncology Branch, member of the Standing Committee of the Oncology Branch of the Chinese Medical Doctor Association Vice-chairman of the Lymphoma Alliance Expert Committee Vice-chairman of the Lymphatic Disease Committee of the Chinese Education Association Vice-chairman of the Precision Medicine Hematology Professional Committee of the Chinese Hospital Management Society 4 Natural Science Foundation and 1 sub-project of major scientific research projects of the Ministry of Science and Technology
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Published 315 academic papers (including 156 Chinese articles and 159 SCI articles) as the first author or corresponding author Editor: Wenting Reviewer: Quinta Typesetting: Uni Execution: Uni poke "read the original text", we will make progress together