2022CSH | Professor Han Weidong: Review and prospect of CAR-T cells in the treatment of hematologic malignancies

The 17th National Hematology Academic Conference of the Chinese Medical Association was grandly opened in Shanghai on September 23-25, 2022, with the theme of "respect, inheritance, collaboration and innovation", and invited well-known experts at home and abroad to talk about the latest progress
in the field of blood diseases.
At the conference, Professor Han Weidong of the General Hospital of the Chinese People's Liberation Army introduced the development and current situation
of CAR-T therapy in the field of hematological tumor treatment under the title of "Review and Prospect of CAR-T Cell Treatment of Malignant Tumors of the Hematological System".

The first case of chronic lymphocytic leukemia (CLL) undergoing CAR-T therapy in 2011 was published in the New England Journal, and now the patient has not recurred for 11 years, and CAR-T therapy has been applied from a single case to the entire population of
patients with blood tumors.
China's regulatory policies in the field of cell therapy are constantly innovating, and the government, hospitals, research institutes, and enterprises are integrated to make the development and trial of CAR-T therapy smoother
.
As a result, progress in CAR-T therapy in China ranks among the highest in the
world.
In addition, domestic clinical trials related to CAR-T therapy involve a variety of targets and hematologic tumors
.
Professor Han Weidong said that China's CAR-T therapy has achieved excellent results, but China currently needs to strengthen its ability to
independently discover therapeutic targets.

In the field of non-Hodgkin lymphoma (NHL) therapy, three CAR-T products targeting CD19, Axicabtagene ciloleucel (axi-cel; ZUMA-1 test), Tisagenlecleucel (tisa-cel; JULIET test) and Lisocabtagene maraleucel (liso-cel; The efficacy of the TRANSCEND trial varied in patients with relapsed/refractory sexually aggressive B-cell lymphoma, with 12-month OS rates of 59%, 48.
2%, and 57.
9%,
respectively 。 The ZUMA series of trials have achieved excellent efficacy in the field of lymphoma treatment, and the results of the ZUMA-7 trial, published in the New England Journal in 2022, show that in patients with relapsed/refractory large B-cell lymphoma, the ORR and CR rates in the axi-cel group and the conventional chemotherapy group were 83% vs 50% and 65% vs 32%, respectively, and the median event-free survival (EFS) was 8.
3 months and 2 months (P<0.
0001),<b11> respectively.
Based on the results of this trial, on April 1, 2022, the FDA approved axi-cel as a second-line therapy
for large B-cell lymphoma.

The exploration of CAR-T therapy in the field of relapsed/refractory NHL therapy does not stop there, and the dual-target CAR-T treatment of B-NHL significantly improves CR rate and PFS
.
The results of an open-label, single-arm 1/2a phase clinical trial published by Professor Han Weidong's team published in the journal BLOOD in 2020 showed that CD19 and CD20 dual-target CAR-T therapy had an ORR of up to 75%
in patients with diffuse large B-cell lymphoma.

In the field of multiple myeloma (MM), researchers initially explored the efficacy
of CAR-T with targets such as CD19 and CD138.
Later researchers found that compared with CD19 and CD138, plasma cells generally express BCMA, and BCMA can promote the maturation and proliferation
of plasma cells.
A 2020 meta-analysis published in the Journal of Hematology & Oncology showed that BCMA-targeted CAR-T therapies had an average ORR of 80.
5% and a median PFS of 12.
2 months
in MM patients 。 Professor Xu Kailin's team at the Affiliated Hospital of Xuzhou Medical University published research data on targeted CD19 sequential BCMA CAR-T therapy in MM patients at Lancet Hematology in 2019, and the results showed that 20/21 patients (95%) achieved objective remission
。 In 2020, the team of Professor Wu Depei of the First Affiliated Hospital of Soochow University released the data of the newly developed targeted CD19 and BCMA dual-target CAR-T therapy in in vivo and abroad of MM, and the results showed that the dual-target CAR-T had significant anti-tumor effects
on MM cells.
Professor Han Weidong said that MM's CAR-T treatment is still being explored, and the newly discovered SLAMF7/CS1 and GPRC5D targets may provide more treatment options
for MM patients in the future.

In 2015, Professor Han Weidong's team published a case in the journal Molecular Therapy of a relapsed/refractory acute myeloid leukemia (AML) receiving targeted CD33 CAR-T therapy that achieved CR and was able to sequentially complete hematopoietic stem cell transplantation (HSCT).

At present, in the field of AML CAR-T therapy, in addition to CD33 targets, CLL1 is also a key target
.
A 2022 study by Professor Wu Depei's team published in the American Journal of Cancer Research showed that two patients with AML who relapsed after allogeneic hematopoietic stem cell transplantation and received targeted CD33 CAR-T therapy achieved complete molecular remission after receiving PD-1 silent targeted CLL1 CAR-T therapy, with a duration of 3 months and 8 months
, respectively 。 Professor Han Weidong said that although CAR-T was developed relatively late in the AML field, it is still moving forward steadily, which is expected to bring new dawn
to patients with relapsed/refractory AML.

Professor Han Weidong concluded that from the above clinical trials, CAR-T therapy has made significant progress
in the treatment of a variety of hematologic tumors.
In addition, issues such as general-purpose CAR-T and car-T-related adverse event management and control are also being further explored, which is expected to bring better and safer CAR-T treatment solutions
to patients.

Professor Han Weidong

• Director of the Department of Biological Therapy of the General Hospital of the People's Liberation Army of Chinese

• Chief physician, professor, doctoral supervisor

• Millions of talents in the country

• Capital science and technology innovation leading talents

• Special expert of the State Council and government

• Former new star of science and technology of the General Logistics Department

• Mainly engaged in the clinical research of tumor treatment resistance mechanism and tumor immunotherapy

• It has undertaken 1 major special project of the Ministry of Science and Technology, 2 973 projects, 3 863 projects, 1 major project of the National Natural Science Foundation of China, 2 key projects, 1 special original, 7 surface projects, 1 frontier project of biotechnology in Beijing, 3 enterprise investments, and 4 clinical treatment technology enterprise transfers

• There are more than 20 national invention patents

• Editor-in-chief of
  3 monographs.
  As the first author or corresponding author, he has published more than 170 SCI papers in academic journals such as JCO, Cell Res, Blood, Nature Cancer, CCR, NAR, JNCI, Nat.
  Comm.
  , JHO, Leukemia and other academic journals, with a cumulative impact factor of more than 1100 points

• Participated in the second prize or above of the provincial and ministerial level

• In 2015, the Professional Committee of Biotherapeutics of Chinese Research Hospitals (Secondary Society) was established and served as the first chairman of the committee

Poke "Read the original article" and go to the micro-official website to get more meeting information