Tazemetostat withdrawn globally for all indications (including follicular lymphoma) due to risk of secondary hematologic malignancies
Tazemetostat (an EZH2 inhibitor approved for relapsed/refractory follicular lymphoma) has been voluntarily withdrawn from the global market due to risk of secondary hematologic malignancies.
In the SYMPHONY-1 trial (a phase 1b/3 randomized placebo-controlled study of tazemetostat combined with lenalidomide plus rituximab for relapsed/refractory follicular lymphoma), 5.7% (18/318) of patients receiving tazemetostat (as of March 6, 2026) developed secondary hematologic malignancies (mainly myelodysplastic syndrome and acute myeloid leukemia); none were reported in the placebo group. Most patients with secondary hematologic malignancies received tazemetostat for 1-3 years. Secondary hematologic malignancies occurred as early as 7.5 months after beginning treatment, and some occurred after stopping treatment.
Tazemetostat was approved in the US by the Food and Drug Administration (FDA) in 2020 for relapsed/refractory follicular lymphoma, as well as metastatic or locally advanced epithelioid sarcoma, under an accelerated approval pathway. Tazemetostat was approved in some countries in Asia, but was not approved in Europe.
小结
定义
病史和体格检查
关键诊断因素
- B symptoms (fever, night sweats, weight loss)
- fatigue/malaise
其他诊断因素
- lymphadenopathy
- splenomegaly
- hepatomegaly
- shortness of breath
- cough
- abdominal discomfort or pain
- headache
- change in mental status
- focal neurologic deficits
- chest pain
- bone pain
- back pain
- jaundice
- pallor
- purpura
- skin lesions
- neurologic abnormalities on exam
- visual abnormalities
- breast pain
- swelling or mass in the breast
- metabolic abnormalities (acute renal injury, tumor lysis syndrome, hypercalcemia)
危险因素
- age >60 years
- male sex
- Epstein-Barr virus (EBV)
- human T-lymphocytotrophic virus-1 (HTLV-1)
- Kaposi sarcoma-associated herpesvirus/human herpesvirus-8 (KSHV/HHV8)
- celiac disease
- HIV
- hepatitis C virus (HCV)
- Sjogren syndrome
- Wiskott-Aldrich syndrome
- ataxia-telangiectasia
- use of immunomodulatory drugs
- organ transplant
- Coxiella burnetii
- rheumatoid arthritis
- systemic lupus erythematosus (SLE)
- hemolytic anemia
- common variable immunodeficiency
- Klinefelter syndrome
- pesticides
- breast implants
诊断性检查
首要检查
- CBC with differential
- comprehensive metabolic panel (including liver function tests [LFTs])
- serum lactate dehydrogenase (LDH)
- uric acid
- lymph node biopsy
- biopsy (extranodal sites)
- bone marrow biopsy and aspiration
- immunohistochemistry
- flow cytometry
- fluorodeoxyglucose (FDG)-PET/CT scan
需考虑的检查
- core needle biopsy
- fine-needle aspiration (FNA) biopsy
- genetic testing
- hepatitis B virus (HBV) serology
- hepatitis C virus (HCV) serology
- HIV testing
- Epstein-Barr virus (EBV) testing
- human T-cell lymphotropic virus (HTLV) testing
- MRI (brain, spine)
- ultrasound (breast, axilla)
- lumbar puncture
- endoscopy
- serum protein electrophoresis with immunofixation
- quantitative immunoglobulins
- serum beta-2 microglobulin
- multigated acquisition (MUGA) scan
- echocardiogram
- ophthalmologic exam (including slit lamp)
治疗流程
aggressive B-cell lymphomas
aggressive T-cell lymphomas
indolent B-cell lymphomas
indolent T-cell lymphomas
撰稿人
作者
Julie E. Chang, MD
SSM Health
Department of Hematology, Medical Oncology, and Palliative Care
Madison
WI
利益声明
JEC has been paid for time served on advisory boards for MorphoSys, BeiGene, and Genentech. JEC has research funding from Genentech and Celgene.
鸣谢
Dr Julie Chang would like to gratefully acknowledge Dr Esther Chan, Dr Chin Hin Ng, Dr Melissa Ooi, Dr Michelle Poon, Dr Boris Kobrinsky, and Dr Kenneth B. Hymes, previous contributors to this topic.
利益声明
EC, CHN, MO, BK, and KBH declare that they have no competing interests. MP has received sponsorship from Sanofi and Janssen to attend conferences.
同行评议者
Leonidas G. Koniaris, MD
Associate Professor Surgery
Department of Cell Biology and Anatomy
University of Miami School of Medicine
Coral Gables
FL
利益声明
LGK declares that he has no competing interests.
Shankaranarayana Paneesha, MD, MRCP, FRCPath
Consultant Haematologist
Department of Haematology and Stem Cell Transplantation
Heartlands Hospital
Birmingham
UK
利益声明
SP declares that he has no competing interests.
Peer reviewer acknowledgements
BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.
Disclosures
Peer reviewer affiliations and disclosures pertain to the time of the review.
参考文献
关键文献
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: B-cell lymphomas [internet publication].全文
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: T-cell lymphomas [internet publication].全文
National Comprehensive Cancer Network. NCCN central nervous system cancers [internet publication].全文
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: primary cutaneous lymphomas [internet publication].全文
Eyre TA, Cwynarski K, d'Amore F, et al. Lymphomas: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2025 Nov;36(11):1263-84.全文 摘要
参考文献
A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
鉴别诊断
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- Acute lymphoblastic leukemia (ALL)
- Infectious mononucleosis
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