In the first half of the year just passed, new drugs with outstanding efficacy continued to be approved for marketing. For hematologic tumors (leukemia, lymphoma, and multiple myeloma), the FDA approved the marketing of one new drug, polatuzumab vedotin, and expanded the indications for several “old” drugs. The FDA approved a new drug, polatuzumab vedotin, and expanded the indication for several “old” drugs.
Our National Medicines and Drug Administration (NMPA) also approved a new drug, carrilizumab, for marketing.
Table New Hematologic Oncology Drugs Approved by US FDA and China NMPA
| Type | Drug or protocol | Indications | |
| United States | Targeted | polatuzumab vedotin | relapsed or refractory diffuse large B-cell lymphoma |
| Ibrutinib + obinutuzumab | First-line treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma | ||
| postline therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma | |||
| Dasatinib | First-line therapy for Ph-positive acute lymphoblastic leukemia | ||
| Lenalidomide + rituximab | Maintenance therapy for follicular lymphoma or marginal zone lymphoma | ||
| ivosidenib | First-line treatment of acute myeloid leukemia with IDH1 mutation | ||
| Daremumab |
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| China | Immunization | Carelizumab | relapsed or refractory classic Hodgkin’s lymphoma |
Below, we describe the use of these new drugs and new indications by the type of cancer for which they are indicated.
Leukemia: “De-chemotherapy” regimens approved, targeted era dawns
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CLL/SLL
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease, which occurs primarily in older adults. In the first half of this year, the FDA approved 2 targeted combination regimens – “ibrutinib + obinutuzumab” and “venetoclax + obinutuzumab” – for all CLL/SLL at once. obinutuzumab”.
In one of these, “ibrutinib + obinutuzumab” is used as first-line therapy for patients with advanced disease, and this is the same FDA that approved de-chemotherapy as first-line therapy for CLL/SLL. The other targeted combination, venetoclax + obinutuzumab, was approved as a second-line therapy.
The approval of these two “de-chemotherapy” regimens signals the growing importance of targeted agents in clinical use.
ALL
A new targeted first-line therapy for acute lymphoblastic leukemia (ALL) is also available this year, with the FDA expanding the indication for the “old” dasatinib to be used in combination with chemotherapy as first-line therapy for patients with PhALL over 1 year of age.
ALL is more common and rapidly progressive in children and adolescents. The accompanying expansion of the indication for dasatinib means that more effective treatment options are available for this group of patients.
AML
Ivosidenib is a new drug that came on the market just last year that inhibits IDH1 mutations. This year, the FDA approved it for first-line treatment of acute myeloid leukemia (AML) with IDH1 mutations.
It is easy to see that for the treatment of leukemia, both gonadal and myeloid leukemia, targeted drugs are playing an important role.
Lymphoma: “De-chemo” options for inert lymphoma, new drugs for relapsed malignant lymphoma
HL
Hodgkin’s lymphoma (HL) is the malignancy with the highest cure rate today. For patients with relapsed disease, we approved a new PD-1 monoclonal antibody, karelizumab, for treatment. In the study, it achieved an objective remission rate of 84.8% in patients who had failed prior therapy, with efficacy no worse than other previously marketed PD-1 monoclonal antibodies.
FL/MZL
Follicular lymphoma (FL)/marginal zone lymphoma (MZL) is an inert lymphoma with slow-growing tumors that are well treated with chemotherapy. However, it is easy to relapse after chemotherapy remission, and once relapsed it can be tricky.
This year, for the first time, the FDA recommended a chemotherapy-free targeted combination regimen – lenalidomide + rituximab – for relapsed FL and MZL.
Both drugs are “old” in lymphoma treatment, with lenalidomide, an immunomodulator, and rituximab, a CD20 monoclonal antibody, effectively slowing the progression of the cancer with a median progression-free survival (PFS) of 39.4 percent. The combination of these two drugs effectively delayed cancer progression, with a median progression-free survival (PFS) of 39.4 months, almost three times that of rituximab monotherapy.
DLBCL
Diffuse large B-cell lymphoma (DLBCL) is highly malignant and very common in the clinic. After standard R-CHOP regimens (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), more than 40% of patients relapse or become resistant.
For this group of relapsing patients, there is a new drug for 2019, polatuzumab vedotin. this is an antibody-coupled drug that specifically targets CD79b, a protein. In studies, this drug combined with bendamustine and rituximab resulted in remission in 40% of patients, far more than the 18% with chemotherapy.
Multiple myeloma: “De-chemotherapy” regimen available for non-transplantable patients, and more effective consolidation therapy for transplantable patients
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Non-transplantable patients
Chemotherapy followed by sequential autologous HSCT is preferred for symptomatic multiple myeloma (active), but chemotherapy is the only option for older patients or those who are unable to transplant for their own reasons.
This year, the FDA approved the regimen “dalimumab + lenalidomide + dexamethasone (DRD)” to treat patients with multiple myeloma who cannot be transplanted.
This combination regimen is chemotherapy-free, but still highly effective. It reduced the risk of disease progression and death by 44% in the trial, which was significantly better than lenalidomide + dexamethasone. The results of the study were published in the New England Journal of Medicine, and this regimen is about to be included in the US NCCN guidelines.
Transplantable patients
For transplant-ready patients, dalimumab combined with bortezomib, thalidomide, and dexamethasone was able to consolidate transplant efficacy, stop disease progression, and significantly extend progression-free survival time.