[A quick look at ASCO's big coffee] Professor Xiao Zhijian: Bellinto Oumab combined with the third-generation TKI, the new Chemo-free solution is expected to replace transplantation!

The 2021 American Society of Clinical Oncology (ASCO) annual meeting will be held online on June 4th.
The heavy research data of hematological tumors at this conference are also rushing to debut.
This morning, Professor Dr.
Nicholas Short of MD Anderson Cancer Center gave an oral report to the center.
A phase II study: early data of CD19-CD3 bispecific BiTE immunotherapy belintouximab combined with third-generation TKI Ponatinib in the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) patients
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Professor Xiao Zhijian from the Hospital of Hematology of the Chinese Academy of Medical Sciences was invited to give an in-depth interpretation of this research
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Professor Xiao Zhijian, Chief Physician, and Doctoral Supervisor, Deputy Director, Hematology Hospital (Institute of Hematology), Chinese Academy of Medical Sciences Director of MDS Clinic Center, Hematology Hospital, Chinese Academy of Medical Sciences Director of Pathology Center, Hematology Hospital, Chinese Academy of Medical Sciences, Chinese Medical Association Deputy Chairman of the Hematology Branch, Leukemia and Lymphoma Group Leader of the Hematology Branch of the Chinese Medical Association won the National Candidate of the "New Century Talent Project", the Ministry of Health "Young and Middle-aged Experts with Outstanding Contributions", and the State Council "Special Government Post" "Expert" and "National Outstanding Scientific and Technological Workers" and other titles such as "Chinese Journal of Hematology", "International Journal of Blood Transfusion and Hematology" and "Leukemia • Lymphoma", deputy editor, "Blood Review", "Gene, Chromosomes and Cancer" etc.
Combination of ponatinib and blinatumomab in Philadelphia chromosome-positive acute lymphoblastic leukemia: Early results from a phase II study.
Research background The complete molecular remission (CMR) of Ph+ ALL patients is associated with better survival prognosis
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Previous studies have proved that both belintouximab and ponatinib can achieve high molecular remission rates in patients with Ph+ ALL
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For example, the combined application of the two drugs may give patients a deeper and lasting remission and reduce the need for allogeneic hematopoietic stem cell transplantation (AHSCT)
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Research Method This is a single-arm phase II study, planning to include adult patients with newly diagnosed (ND) and relapsed/refractory (R/R) Ph+ ALL
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Patients received standard doses of belintoux infusion for up to 5 consecutive cycles
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Ponatinib was given 30 mg daily at the beginning of the first cycle.
If the patient reached CMR, Ponatinib was reduced to 15 mg daily
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After completion of belintoxumab treatment, patients who get a response should receive Ponatinib for at least 5 years
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The enrolled patients received 12 doses of preventive intrathecal chemotherapy
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The primary endpoint of ND patients is the CMR rate, and the primary endpoint of R/R patients is the overall response rate (CR/CRi rate)
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Study results 1 Status of enrolled patients A total of 30 patients were enrolled, including 20 patients with ND Ph+ ALL, with a median age of 62 years (34-83 years), and 70% of patients were P190 fusion protein
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R/R Ph+ ALL patients: 10 cases, with a median age of 36 years (24-61 years)
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Nine patients had P190 fusion protein, and 5 patients were on ≥2 line salvage treatment
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2 Depth of relief There was no early death within 4 weeks of this program
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The overall treatment response rate of the enrolled patients was 95.
6%, and the CMR rate was 86%
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Among them, the treatment response rate of ND patients was 100%, of which 85% obtained CMR; the treatment response rate of R/R patients was 89%, and 88% obtained CMR
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The median time to CMR is 1 month (1-13 months)
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3 Survival time ND patients did not receive AHSCT; 4 R/R patients received AHSCT
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With a median follow-up of 12 (1-37) months, the 1-year OS rate for the entire study population was 93%, and the EFS rate was 76%
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There was no recurrence in the ND group.
One patient reached CR but died of postoperative hemorrhage and hypovolemic shock.
The 1-year and 2-year OS and EFS rates of ND patients were 93%
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The 1-year OS rate in the R/R group was 80%, and the 2-year OS rate was 53%
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4 Safety The program is well tolerated
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Most side effects were grade 1-2, and there were no cases of discontinuing Ponatinib due to toxicity
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Only 1 patient discontinued belintoxumab due to recurrent grade 2 tremors
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The conclusion of the study is that the chemo-free combination regimen of belintuomab and ponatinib has shown encouraging results in the treatment of Ph+ ALL patients
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This program allows patients to obtain a higher CMR rate and lasting remission, and is expected to reduce the need for chemotherapy and allogeneic transplantation, especially as a first-line treatment for newly diagnosed patients
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In the past few years, as the results of clinical trials of molecularly targeted drugs for the pathogenesis of hematological tumors and single/biclonal antibodies that abnormally express antigens on tumor cells/tumor cells’ survival microenvironment have been announced, some results have been released.
It's really exciting
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Hematopoietic stem cell transplantation is the only method for some hematopoietic and lymphoid tissue tumors so far, but the results of clinical trials of new drugs in recent years suggest that chemotherapy-free (chemo-free) holistic treatment strategies are expected to become a new option for some hematological tumor patients
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Belintoomab is a bispecific antibody that targets CD3+ T cells to B-ALL tumor cells and exerts a tumor-killing effect
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Belintolomab is currently on the market in China for the treatment of R/R B-ALL patients
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Previously, there have been many attempts at the chemo-free solution of belintoux and TKI.
In October 2020, a phase II study of belintoux and second-generation TKI was published in the New England Journal.
As a result, 63 adult patients with ND Ph+ ALL received dasatinib induction therapy.
After the induction therapy, the consolidating therapy with belintoumab further deepened the molecular remission
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After dasatinib induction, 98% of patients achieved CR but only 29% of patients achieved CMR
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After 1 cycle of Sequential Belintuzumab, 64% of patients received CMR
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And with the increase in cycles, the proportion of patients with CMR has further increased, reaching a maximum of 81%
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The OS rate at a median follow-up of 18 months was 95%, and the disease-free survival (DFS) rate was 88%
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Six patients had increased minimal residual disease (MRD) levels during the dasatinib induction stage and had a T315I mutation.
The remaining mutations in these patients were cleared after sequential belintoomab treatment, suggesting that belintoomab Therapies against different mechanisms of action may overcome the T315I mutation
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2 According to the results of the study reported by ASCO, newly diagnosed Ph+ ALL patients did not undergo sequential allogeneic transplantation after receiving the induction therapy with belintouximab combined with Ponatinib, and all patients had no recurrence for 1 year, suggesting that this type of immune combination The chemo-free program may shake the status of allogeneic hematopoietic stem cell transplantation in such patients in the future, but it still needs to be further confirmed by prospective, multi-center, randomized controlled clinical trials
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References: 1,2021 ASCO abstract#7001.
Combination of ponatinib and blinatumomab in Philadelphia chromosome-positive acute lymphoblastic leukemia_ Early results from a phase II study.
2, Kamachi K, Ureshino H.
Dasatinib-Blinatumomab for Ph-Positive ALL.
N Engl J Med.
2021 Jan 28;384(4):384.
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