2022 SHS Professor Wang Xin: From the perspective of big coffee, the treatment of recurrence after ALL transplantation is explored

In China, the incidence of ALL in acute leukemia is high, and the incidence and cure rate of adult ALL are low, the 5-year survival rate of patients is less than 30%, and the refractory or relapsed (R/R) ALL patients after induction therapy are up to 60%, so the efficacy of adult ALL is worse
than that of children's ALL.

Throughout the history of the treatment of adult ALL, before 2000, chemotherapy was the main treatment, and the overall prognosis was extremely poor; Later, with the emergence of tyrosine kinase inhibitors (TKIs), the prognosis of adult Ph⁺ ALL patients improved; In the past decade, the application of new drugs such as small molecule targeted drugs, immunotherapy drugs and cell therapy drugs has further improved
the efficacy of adult ALL patients in China 。 Among them, immunotherapy drugs include monoclonal antibodies, bispecific antibodies, antibody conjugate drugs (ADCs), especially the CD3-CD19 bispecific antibody berintoumab and the ADC okaituzumab targeting CD22 that have been marketed in China, so that the efficacy of ALL patients in China has been improved, although there has not been a significant improvement in survival, but these two drugs in induction therapy (including early induction therapy for elderly ALL patients), Adults with ALL have shown good efficacy
in both consolidation therapy and maintenance therapy.
In addition, CAR-T therapy has also achieved good efficacy
in the treatment of patients with R/R ALL.
In addition, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still an effective treatment option for patients with R/R ALL, and even sequential allo-HSCT can be obtained
after early induction therapy in ALL patients.

Yimaitong: How should I choose a treatment plan for ALL patients who fail transplant treatment?

Post-transplant recurrence in ALL patients is a major problem for hematologists at present, including the occurrence of graft-versus-host disease (GVHD) that prevents patients from better maintenance therapy, resulting in minimal residual disease (MRD) turning positive, and the trend of disease recurrence, which is a very challenging problem
for transplant doctors.

If the patient develops MRD conversion after transplantation, chemotherapy can be followed by a donor lymphocyte infusion (DLI), or immunotherapy such as belintoumab, ogayituzumab, or in combination with chemotherapy
.
In addition, CAR-T therapy is currently one of
the most effective salvage treatment options for relapsed ALL after transplantation.
Nowadays, China's CAR-T clinical research is in the leading position in the world, and domestic hematopoietic stem cell transplantation experts and cell immunotherapy experts are committed to developing more "CAR", including CAR-NK therapy, general-purpose CAR-T, etc.
, to improve the therapeutic effect of
ALL patients.

Whether it is a patient with R/R after transplantation or a patient with R/R ALL after transplantation, it is necessary to closely monitor the condition and do a good job of maintenance therapy to prevent the recurrence of the
disease.
For example, after Ph⁺ ALL patients are transplanted, TKI drug maintenance therapy is required to achieve better results
.
In addition, small molecule targeted drugs such as BCL-2 inhibitors, IDH inhibitors, BTK inhibitors, etc.
, can be combined with immunotherapy to achieve better efficacy for patients, which is also what hematologists need to pay attention to
.

Emmaitong: Combined with the latest advances in overall ALL treatment, what treatment options do you think may further optimize patient outcomes? And in the research and development of new drugs for ALL treatment, what other new directions are worth exploring?

Previously, ALL treatment only had multi-drug combination chemotherapy regimens, including routine VDCLP and Hyper-CVAD regimens, which had some efficacy for patients, and emerging targeted drugs undoubtedly have better efficacy, such as TKI in Ph⁺ ALL patients, and immunotherapy drugs such as CD3-CD19 bispecific antibodies and CD22-targeting ADCs, which can be described as bringing new therapeutic hope
to ALL patients 。 Antibody drugs are currently a more optimistic class of drugs in China, which are exploring the aspects of induction therapy, consolidation therapy, bridging therapy before hematopoietic stem cell transplantation (including allo-HSCT and autologous hematopoietic stem cell transplantation) and maintenance therapy after transplantation, and have also achieved good results, and the results are very exciting
.

When it comes to CAR-T therapy, it is mainly suitable for R/R ALL patients in the ALL population, especially R/R ALL patients
receiving third-line therapy.
So, can CAR-T therapy be advanced to second-line therapy to improve the efficacy of ALL patients? Is sequential hematopoietic stem cell transplantation after CAR-T treatment, especially allo-HSCT, more effective? These are all worth exploring
.

Prof.
Xin Wang

• Director of the Department of Hematology, Shandong Provincial Hospital

• Doctoral supervisor

• Dean of Clinical Medical College of Shandong University Outstanding Talent System Second-level Professor

• Distinguished Professor of the Taishan Scholar Climbing Program

• The Ministry of Health has made outstanding contributions to young and middle-aged experts

• Specially appointed expert on special allowance of the State Council

• Chairman of the Hematology and Tumor Translational Medicine Branch of the Chinese Anti-Cancer Association

• Standing Committee Member of Hematology Branch of Chinese Medical Doctor Association

• Member of Hematology Branch of Chinese Medical Association

• Chairman of the Hematology Branch of Shandong Medical Association

• Chairman of the Diagnostic Branch of Shandong Medical Association

• Vice Chairman of Hematology Branch of Shandong Medical Association

• Member of the American Blood Association ASH