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| Tong-Yu Lin MD Professor Leading Physician, Lymphoma Program Sun Yat-Sen University Cancer Center Source:Oncology Frontier(肿瘤瞭望) |
The Particularity of Immunotherapy
The hot topics at ASCO 2015 would be no doubt ImmunoTherapy.
ImmunoTherapy (including Immuno- Target-Therapy) is currently the most "revulotionary 颠覆性" treatment. At this year's ASCO, everyone's eyes are on PD - 1/PD - L1, on how to find related biomarkers for appropriate patient populations.
Nivolumab (NIVO) and Pembrolizumab (Pembro) originally used for the treatment of melanoma.
NIVO now has been approved by the US FDA for the treatment of squamous non small cell lung cancer, and US FDA has given Nivolumab breakthrough status in the treatment of patients with Hodgkin's Lymphomas (HL) after having been failed autologous stem cell transplantation and Brentuximab treatments.
Promising future
At ASCO 2015, we can see that the existing clinical studies are to explore NIVO curative effect in the use of non-small cell lung cancer.
Last year, at Saint Antonio Breast Cancer Symposium (SABCS), NIVO's research has extended to breast cancer.
At ASH 2014, studies found that even after Hodgkin's Lymphoma patients failed to first line, second, third, fourth, fifth line chemotherapy, even after stem cell transplantation failure, Immunotherapy still are effective in about 50% of the patients.
Single drug or drug combinations clinical research for the treatment of multiple tumor types--including non-small cell lung cancer(NSCLC), small cell lung cancer, head and neck cancer, melanoma, renal cell cancer, liver cancer, lymphoma, multiple myeloma, three negative breast cancer, gastric cancer, pancreatic cancer, bladder cancer and prostate cancer, are under way.
A few tough questions
Biomarkers
Although Immunotherapy has shown "miracle-like神奇的" effect， however, special attention should be paid to patients and dosage selection.
For example, reports show MMR gene deficient with many BRAF V600 mutations in colon cancer patient response better; but, for melanoma, it's effective in patients with BRAF mutation V600 wild type, as well BRAF mutation V600 (+) patients.
Further study is needed to find out the relationship between effect and gene mutation. To unveil the mysteries of those cancer biomarkers on immunotherapy efficacy, research collaboration in the globe is needed.
Dosage
Looking at their dosage wide ranges, NIVO is from 0.3 mg/kg to 10 mg/kg, while Pembro is from 2 mg/kg to 10 mg/kg.
For specific patients, what are the appropriate dosages?
To address Individual factors, such as genetic pharmacology study is very important.
Combination therapy
How to combine immunotherapy agents with target therapy agents and chemotherapy drugs?
A long way to go.
Side effect
LBA1 trial shows that although NIVO with Ipilimumab(IPI) is more effective than single agent, but 50% patients reported adverse effects.
Auto immune reaction in patients should be observed closely by clinicians.
Cost-effective
As Immuno target therapy agent prices are very expensive, cost effective study would help to find out appropriate treatment for patients.
Target therapy highlights in Lymphoma
Studies in lymphoma have taken the lead on cancer targeted therapy.
In 2014, US FDA has approved seven new tumor targeted drugs, and four of them are used in the treatment of lymphoma, 2 drug's application is associated with lymphoma.
Not much big progresses released in lymphoma, just a few ongoing large clinical studies of B cell lymphoma targeted therapy and the preliminary results of new targeted drugs released at ASCO 2015.
Diffused Large B Cell Lymphoma(DLBCL)
Single monoclonal antibody against B cell surface CD20 antigen, such as R-CHOP (Rituximab plus Cyclophosphamide + Doxorubicin + Vincristine + Prednisone) is the baseline for the treatment of B cell lymphoma.
In diffuse large B cell lymphoma, at least a third of patients have disease progression or recurrence in the R-CHOP. For high-risk patients, the percentage is even higher, nearly two-thirds of patients will progress or recur after R-CHOP treatment.
So how to improve the therapeutic efficacy in these patients?
It is important to identify patients with high-risk subtype, then give corresponding treatment.
For high-risk patients, all kinds of research on anti CD20 monoclonal antibody + chemotherapy, other B cell antigen, monoclonal antibody + chemotherapy , R-CHOP + X (different drugs) are under way.
X could be Lenlidomide, Ibrutinib, Everolimus, Bortezomib or CD30 monoclonal antibody.
If CD30 positive , we could choose it's AB, ALK positive for Crizotinib.
Indolent B Cell Lymphoma
There are many drug research on indolent B cell lymphoma. Such as target CD19, triplet in combination of monoclonal antibody with BTK inhibitor, PI3Kδ inhibitor.
In the case of patients in late stage but with long life expectancy, although no cure, efficacy and quality of life should be well balanced.
T/NK cell Lymphoma
The study of the high risk factors, different kinds of potential of targeted drugs in combination of chemotherapy are hot in T/NK cell lymphoma.
Such as CD 30 AB in combination of CHOP to treat anaplastic large cell lymphoma (ALCL); HDACi research is going on; anti PD-1 could be one possible choice too.
T/NK is more prevalent in Asia, so more research contribution from Asian peers are needed.
Reference:
1.【ASCO 2015】林桐榆教授谈肿瘤免疫靶向治疗 “中国医学论坛报今日肿瘤”微信公众号
2. Video [ASCO访谈]林桐榆教授：聚焦淋巴瘤治疗进展，关注肿瘤患者生存质量, 《肿瘤瞭望》微信公众号
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