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In the first two years, the movie "I Am Not a Medicine God" was a hit, which not only directly hit the pain point of high modern medical costs, but also brought leukemia into the public's vision again.
Leukemia is a heterogeneous group of hematopoietic malignancies caused by differentiation blockade, apoptosis disorders, and malignant proliferation of hematopoietic stems/progenitor cells. According to the length of the disease course, the degree of differentiation, etc., leukemia can be divided into acute and chronic, according to the classification of diseased cells, it can be divided into granular, single, red, megakaryotic and lymphoid T and B cell lines of the medullary system.
For the treatment of leukemia, generally includes chemotherapy drugs, immunotherapy, immunotherapy includes immune targeted therapy, cellular immunotherapy and so on. Compared with chemotherapy drugs, targeted therapy and cellular immunotherapy can selectively kill tumor cells. In addition, as more tumor cell targets are discovered, targeted therapy and immunotherapy are gradually surpassing chemotherapy drugs.
Anti-CD20 monoclonal antibodies for CLL
Immunotherapy is mainly combined with characteristic antigens expressed on the surface of leukemia cells to selectively kill tumor cells. Clinically, there are already many monoclonal antibodies used to treat leukemia.
Rituximab, an anti-CD20 monoclonal antibody. CD20, a cell surface antigen specifically expressed by B cells, can induce B cell lysis through a variety of mechanisms, and is expressed at all stages of the cell cycle of malignant B cells.
With the application of rituximab (anti-CD20 monoclonal antibody), the treatment of B-cell malignancies has made great progress.
The second generation of anti-CD20 monoclonal antibody - offamumab is introduced
Rituximab, after combined with conventional chemotherapy, significantly improves complete response and overall survival. But as rituximab gradually developed drug resistance, other CD20 monoclonal antibodies emerged, such as omalimumab. While most patients with CLL respond well to first-line treatment, the disease eventually progresses, and the use of limited drug therapy after that is also driving the creation of new drugs.
Ofamumab, is the second generation of anti-CD20 monoclonal antibodies, compared with the first generation of antibodies such as rituximab, the immunogenicity of omalimumab is greatly reduced, complement-dependent cytotoxicity will be stronger, degradation rate will be slower. It can be used not only as a salvage treatment regimen when rituximab therapy is ineffective, but also as a first-line treatment option for lymphatic malignancies.
Compared with rituximab, omalimumab is more advantageous in the treatment of chronic lymphocytic leukemia (CLL).
The most prominent feature of osemumab is that it is different from the binding position of rituximab, and the treatment of oleimumab can significantly improve the median survival of CLL patients. Data from a phase III study showed that of 474 patients, patients treated with otalimumab had a median survival of 13.4 months longer than those who did not receive further treatment.
In 2011, based on the results of a Phase II study, the FDA approved that oshalimumab can be used to treat chronic lymphocytic leukemia (CLL) that does not respond to fludarabine and alemizumab therapy; in 2016, based on a randomized Phase III clinical trial, the FDA approved omalimumab for patients with recurrent/progressive chronic lymphocytic leukemia (CLL) who have received at least 2 previous treatments and achieved complete remission (CR) or partial remission (PR).
Clinical efficacy of omalimumab
In an article on adult acute lymphoblastic leukemia published in the journal Blood, a study was done in which the duration and overall survival of CR at 3 years were 78% and 68% in 59 patients who received treatment, respectively, and the incidence of adverse reactions did not increase.
Secondly, in a phase II clinical trial, patients with relapsed/refractory chronic lymphocytic leukemia were given weekly treatment with omalimumab, the first week was intravenously 100 mg, 300 mg or 500 mg, and in the subsequent 3 weeks, 500 mg, 1000 mg or 2000 mg, respectively, and these patients have received 3 treatments. Clinical data from this trial indicate that the ORR of omalimumab is 50%.
In addition, in a multicenter phase III study abroad, clinical data showed that oflumab was well tolerated, and its therapeutic effect was comparable to rituximab.
In summary, although rituximab may improve prognosis in early CLL treatment, its effect is still limited, and part of the reason may be related to the reduction of complement-dependent cytotoxicity and cell lysis. Clinical trial data show that at the corresponding dose level, oselmumab is significantly superior to rituximab when lysating CLL cells and B cell lines. The most important point is that several trials have shown that ofamumab causes few adverse reactions.
Dosage of omalimumab
In general, intravenous treatment with ofamumab is given at a starting dose of 300 mg.
Depending on the indications, the dosage of ofamumab administered varies.
1. For untreated CLL patients: o'falimumab combined with chlorambucil, it is recommended that in the first cycle, the amount of the first day is 300mg, and the dosage of the 8th day is 1000mg; for 28 days as a cycle, in the subsequent cycle, the first day of the dosage is 1000mg. At least 3-12 cycles of medication.
2. For patients with recurrent CLL: the amount of medication on the first day is 300mg, and the dosage on the eighth day is 1000mg; then it is still a cycle of 28 days, and the medication time does not exceed 6 cycles.
3. For patients with refractory CLL: the first dose is 300mg; after one week of treatment, the subsequent weekly dosage is 2000mg, a total of 7 times; after four weeks of use, the dose is 2000mg every four weeks, a total of 4 times.
4. For the extended treatment of CLL patients: in the first cycle, the dosage on the first day is 300mg, and the dosage on the eighth day is 1000mg; in the subsequent cycle, the dosage is 1000mg after 7 weeks, and 1000mg is used every 8 weeks thereafter, and the medication does not exceed 2 years.
In addition, 1000 mg of acetyl (or equivalent) should be taken orally for the first 30 minutes to 2 hours of administration of ofamumab therapy, plus oral or intravenous antihistamines, plus intravenous corticosteroids.
For patients who are eligible for treatment with ofamizumab, it is necessary to remind that it should be used strictly according to medical advice and under the guidance of a doctor.
Application prospects of ofofamumab
Since the drug is not currently listed in China, the price is not clear. For offamumab, it can be used not only to treat CLL, but also to treat adult patients with recurrent multiple sclerosis.
For patients with chronic lymphocytic leukemia, what is needed is a more effective, safe and well-tolerated treatment plan to improve their prognosis, and we hope that more patients can conditionally apply this drug to alleviate their own pain. Due to the high cost of monoclonal antibodies, whether it is research and development or imitation, it requires high costs, and with the continuous advancement of technology, it is expected that domestic patients can also use this drug as soon as possible.
cite
EliasJabbourandHagopKantarjian.Immunotherapyinadultacutelymphoblasticleukemia:theroleofmonoclonalantibodies[J]. Blood,2016,1(3):260-264.
Susan O’Brien andAnders sterborg. Ofatumumab:ANewCD20Monoclonal AntibodyTherapyforB-CellChronicLymphocytic Leukemia[J]. Clinical Lymphoma, Myeloma & Leukemia,2010,10(5):361-368.