The Rise of Immunocell Therapy and the Era of “Farewell to Chemotherapy”

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The Rise of Immunocell Therapy and the Era of “Farewell to Chemotherapy”

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The Rise of Immunocell Therapy and the Era of “Farewell to Chemotherapy”

71.4% of Tumor Patients Have No Recurrence! Entering the Era of “Farewell to Chemotherapy,” Immunocell Therapy Eradicates Cancer Cells from the Root.

Adjuvant chemotherapy, also known as preventive chemotherapy, refers to the administration of chemotherapy after the visible tumor has been surgically removed in order to reduce the risk of recurrence and metastasis, considering potential undetectable metastasis or a small number of cancer cells that may have escaped into the bloodstream after surgery.

However, is chemotherapy always necessary for cancer treatment?

Indeed, chemotherapy has long been one of the mainstays of anti-tumor treatment. With advances in medical research, the era of “de-chemotherapy” has quietly arrived, and new anti-tumor strategies represented by immunocell therapy have emerged, bringing new hope to cancer patients.

Adjuvant chemotherapy only increases the survival period by 5%, with limited efficacy.

Chemotherapy can be subdivided into adjuvant chemotherapy, neoadjuvant chemotherapy, curative chemotherapy, and palliative chemotherapy, depending on its form.
Adjuvant chemotherapy: It clears residual cancer cells and tiny metastases in the body after surgery, and is mainly used for early to mid-stage cancer.

Neoadjuvant chemotherapy: It is used for mid-stage cancer patients and those with tumors that are difficult to completely remove surgically, aiming to improve the patient’s condition and create favorable conditions for subsequent surgery or radiotherapy.

Curative chemotherapy: Chemotherapy aimed at curing cancer, some malignant tumors such as leukemia and lymphoma are sensitive to chemotherapy drugs, and cure can be achieved solely through chemotherapy.

Palliative chemotherapy: Mainly used for advanced cancer patients for whom cure is not possible, the main purpose is to reduce the tumor burden, control further spread of cancer cells, improve the quality of life as much as possible, and extend survival.

However, all types of chemotherapy face problems such as toxic side effects and limited efficacy. While chemotherapy drugs can eliminate tumor cells, they also damage normal cells in the body, leading to side effects such as digestive disorders and bone marrow suppression.
Research shows that adjuvant chemotherapy can benefit patients with NSCLC (non-small cell lung cancer) in terms of survival, but the benefit in terms of overall survival (OS) is relatively limited, with an increase of only about 5%.

In clinical practice, the later the stage of non-small cell lung cancer, the greater the benefit of adjuvant chemotherapy. Currently, major clinical guidelines do not recommend adjuvant therapy for stage IA, only considering adjuvant therapy for patients with high risk of recurrence in stage IB, and recommending platinum-containing chemotherapy as adjuvant therapy for stage IIA/B and IIIA. However, the efficacy of adjuvant chemotherapy is still not ideal, with a 45% 5-year recurrence rate for IB patients, a 62% 5-year recurrence rate for II patients, and a high 76% 5-year recurrence rate for III patients.

At the 2023 ASCO meeting, the latest OS data from the ADAURA study was announced, showing that the 5-year OS rate of stage II-III A NSCLC patients receiving osimertinib adjuvant therapy reached 85%, significantly higher than the 73% in the placebo group.

Subgroup analysis showed that the 5-year survival rates of patients who received and did not receive adjuvant chemotherapy were similar, at 87% and 88% respectively, an increase of about 10% compared to the placebo group. These data provide evidence for adjuvant therapy without chemotherapy for EGFR mutation patients.

In addition, although neoadjuvant therapy has more potential than adjuvant therapy in reducing tumor stage and eliminating micro-metastasis, the 5-year survival rate of patients receiving neoadjuvant chemotherapy only increased by about 5%.

The objective response rate of immunotherapy combined therapy increased by 17.4%, “de-chemotherapy” is imperative!

At the 2022 ESMO Congress, the latest data from the SUNRISE study was announced, bringing new ideas to cancer treatment – the “de-chemotherapy” model. This is an open-label, multicenter, randomized phase II study that included NSCLC patients in stage IV, untreated, and negative for EGFR/ALK/ROS1.
As of July 15, 2022, the efficacy of 40 patients in the sintilimab combined with anlotinib group (immunotherapy + targeted therapy) and 43 patients in the chemotherapy group (including platinum) could be evaluated.

The ORR (objective response rate) of the “immunotherapy + targeted therapy” group reached 50%, while the ORR of the chemotherapy group was 32.6%, and regardless of PD-L1 expression, the “immunotherapy + targeted therapy” group benefited.

The median duration of response (DOR) in the “immunotherapy + targeted therapy” group and the chemotherapy group was 16.3 months and 6.2 months respectively, the median PFS (progression-free survival) was 10.8 months and 5.7 months respectively, with a hazard ratio (HR) of 0.4, indicating a 60% reduction in the risk of disease progression, P=0.002.
Compared with traditional chemotherapy, immunotherapy has the advantages of durable response, high cure rate, minimal toxicity, and high quality of life for patients. At the same time, immunotherapy alone has limited efficacy, and not all NSCLC patients can benefit from immunotherapy. In terms of clinical protocol selection, there is a greater tendency towards combination immunotherapy.

Immunocell therapy eradicates recurrence from the root, with 71.4% of tumor patients having no recurrence!

In June 2022, the international renowned journal “Cancer Immunology Research” published an article on the DC vaccine combined with adoptive T-cell therapy for liver cancer.

“Cancer Immunology Research” screenshot

This is the world’s first dendritic cell (DC) vaccine based on tumor neoantigens combined with adoptive T-cell therapy for the prevention of liver cancer recurrence in a phase II clinical trial.
This study recruited 10 patients who underwent radical resection or radiofrequency ablation (RFA) for hepatocellular carcinoma, and all patients received adjuvant combined immunotherapy according to the protocol (each infusion of 1.65×106–18.8×106 DC cells and 0.56×106–8.12×109 neoantigen-activated T cells).
The results showed that, among the 10 patients, 5 (50%) did not experience recurrence within 2 years after radical treatment; the median DFS was 18.3 months.

At the same time, 7 patients (70%) had an immune response to multiple predicted epitopes, known as responders, while the other 3 patients did not produce an IFNγ response to the peptide stimulation used in the treatment, known as non-responders.

The median disease-free survival (DFS) after treatment was 18.3 months, and patients with immune responses had a significantly longer DFS than those without immune responses, with 71.4% of immune responders not experiencing recurrence within 2 years after radical treatment.

Further research found that patients with hepatocellular carcinoma who exhibited characteristics such as high tumor mutation burden, enrichment of DC and CD8+ T cells, and high expression of T cell-related genes in the primary tumor were more likely to benefit from combination immunocell therapy.

In terms of treatment safety, among the 10 patients, only 1 experienced grade 2 or 1 treatment-related adverse event, with no grade ≥3 treatment-related adverse events or treatment-related deaths, demonstrating the clinical anti-tumor efficacy and safety of the therapy.

In conclusion, with the emergence of new anti-tumor therapies and the accumulation of evidence-based medicine data, many “de-chemotherapy” regimens are beginning to show promise, offering the potential to further improve the quality of life and extend the survival of cancer patients.

Today, medicine is developing rapidly, and future anti-tumor treatment regimens will be more precise, efficient, and safe. We will find that the era of “farewell to chemotherapy” is not just a concept; it will become a reality. Precision medicine, represented by immunocell therapy, will become an important direction for future anti-tumor treatment, accelerating the arrival of the “de-chemotherapy era” and benefiting more patients.

The Rise of Immunocell Therapy and the Era of “Farewell to Chemotherapy”

References:

[1]Masahiro Tsuboi, M.D., Roy S. Herbst, M.D., Ph.D.et al. Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. June 4, 2023,NEJM.DOI: 10.1056/NEJMoa2304594
[2]Baohui Han,Tianqing Chu,Zhuang Yu,et al.Sintilimab plus anlotinib versus platinum-based chemotherapy as first-line therapy in metastatic NSCLC(SUNRISE):an open label,multi-center,randomized,phase 2 study.2022ESMO.
[3]Peng S, Chen S, Hu W, Mei J, Zeng X, Su T, Wang W, Chen Z, Xiao H, Zhou Q, Li B, Xie Y, Hu H, He M, Han Y, Tang L, Ma Y, Li X, Zhou X, Dai Z, Liu Z, Tan J, Xu L, Li S, Shen S, Li D, Lai J, Peng B, Peng Z, Kuang M. Combination Neoantigen-Based Dendritic Cell Vaccination and Adoptive T-Cell Transfer Induces Antitumor Responses Against Recurrence of Hepatocellular Carcinoma. Cancer Immunol Res. 2022 Jun 3;10(6):728-744. doi: 10.1158/2326-6066.CIR-21-0931. PMID: 35476700.

(source:internet, reference only)

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