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Can Carfilzomib Change The Clinical Therapeutic Decision Of MM?

Shanghai Chiral Chemicals Inc | Updated: Jul 13, 2017

  Can Carfilzomib change the clinical therapeutic decision of MM?

  With the advent of a variety of new drugs, such as boron and bortezomib, the therapeutic strategies of multiple myeloma (mm) have also changed significantly. Although in the past 10 years, traditional therapies such as the United States of America and the wider application of prednisone, but for the time being, the treatment has gradually become a history. Dexamethasone + Boron bortezomib/To that degree of amine has become the new diagnosis of MM and recurrence of the treatment of MM backbone. In order to further improve the efficacy of dexamethasone + boron bortezomib in the treatment of MM, researchers have made a lot of attempts. A randomized 3-phase trial was performed to compare the efficacy of boron bortezomib + thalidomide + dexamethasone and thalidomide + dexamethasone in the treatment of patients with recurrent mm. Although the results showed that the progression of progression-free survival and progress in patients with triple therapy was significantly longer than those treated by two-phase therapy, the incidence of 3-4-level adverse reactions was higher (29% vs 12%).

  The new combination therapy, including boron bortezomib + cyclophosphamide + dexamethasone and boron bortezomib + to the degree of amine + dexamethasone, reduced the remission rate from 5% to 15%, and the two combined therapies had been used for the first-line treatment of MM. At the same time, the change of bortezomib from intravenous injection to subcutaneous injection reduced the rate of multiple neuropathy.

  Therefore, if the Bortezomib combination therapy is available and the multiple neuropathy is no longer a problem, then is the second-generation proteasome inhibitor such as the card-like meter applicable to mm? A study published in the journal Lancet Oncology compared the clinical efficacy of bortezomib + Carfilzomib dexamethasone and boron-bortezomib + dexamethasone in the treatment of patients with relapsed/refractory mm after 1-3 treatments. The results showed that the progression-free survival rate, complete remission rate and remission duration of Carfilzomib group were better than that of boron bortezomib group.

  In addition, the incidence of 3-stage peripheral neuropathy (No. 4) in the Carfilzomib group was 2%, while in the Boron bortezomib group, although most patients were treated with subcutaneous injection, the incidence of 3-4-stage peripheral neuropathy was 8%. Although the study provides strong evidence for the combination therapy, Carfilzomib it is still in two different situations. First, many patients with large doses of United States and autologous stem cell transplants received a dose of amine maintenance treatment, and based on first studies, 10 patients who were not suitable for transplant received the dose of amine + dexamethasone to treat the disease. Therefore, in future clinical treatment, there will be more patients with the disease progression after the treatment of amine need to undergo second-line treatment. In the ENDEAVOR study, the patients were treated by the amine after the treatment, most of the development of refractory mm, and these patients by Carfilzomib treatment did not produce better than the clinical benefits of boron bortezomib. In Aspire study, Carfilzomib showed obvious synergistic effect on the degree of amine + dexamethasone.

  Endeavor and Aspire studies have shown that after the treatment of the degree of remission of the MM patients need to receive second-line treatment, and the card is not bortezomib + Carfilzomib dexamethasone or low dose of bortezomib + to the amine + dexamethasone is a good second-line treatment options. For those who come to that degree, it is not clear whether the treatment is still applicable, especially in conjunction with-, a combination of such drugs. Most of the studies were to investigate the efficacy of the amine + dexamethasone in addition to the refractory mm, so the follow-up study needed to identify the best treatment for the patients with refractory mm.

  Second, it takes extra care to treat patients with severe kidney damage. The ENDEAVOR study excluded creatinine clearance rate ≤15 ml/min, and only 28 patients in each group were ≤30 ml/min. There was no significant difference in the progression-free survival period between the two groups. In addition, the incidence of acute renal failure in Carfilzomib group was higher than that of boron bortezomib Group (8% vs 5%). Therefore, Carfilzomib unless more data are available to demonstrate the safety and efficacy of Carfilzomib in the treatment of patients with severe renal impairment, boron-bortezomib is still a better choice for such patients.

  Although these limitations exist at present, the Endeavor study has clarified that Bortezomib + dexamethasone can be used as a standard therapy for patients with relapse or refractory mm (suitable proteasome inhibitor therapy). The therapy provides a new benchmark for the combination of two drugs in the treatment of 1-3 previously treated mm patients.