Myelodysplastic Syndromes: 2023 Update on Diagnosis, Risk-Stratification, and Management PDF

Received: 2 April 2023 Revised: 21 May 2023 Accepted: 23 May 2023 DOI: 10.1002/ajh.26984 ANNUAL CLINICAL UPDATES IN HEMATOLOGICAL MALIGNANCIES Myelodysplastic syndromes: 2023 update on diagnosis, risk-stratification, and management Guillermo Garcia-Manero Section of MDS, Department of Leuke...

Received: 2 April 2023 Revised: 21 May 2023 Accepted: 23 May 2023 DOI: 10.1002/ajh.26984 ANNUAL CLINICAL UPDATES IN HEMATOLOGICAL MALIGNANCIES Myelodysplastic syndromes: 2023 update on diagnosis, risk-stratification, and management Guillermo Garcia-Manero Section of MDS, Department of Leukemia, University of Texas MD Anderson Cancer Abstract Center, Houston, Texas, United States Disease overview: The myelodysplastic syndromes (MDS) are a very heterogeneous Correspondence group of myeloid disorders characterized by peripheral blood cytopenias and increased Guillermo Garcia-Manero, Anderson Cancer risk of transformation to acute myelogenous leukemia (AML). MDS occurs more Center, 1400 Holcombe Blvd, Houston, TX 77030, USA. frequently in older males and in individuals with prior exposure to cytotoxic therapy. Email: [email protected] Diagnosis: Diagnosis of MDS is based on morphological evidence of dysplasia upon Funding information visual examination of a bone marrow aspirate and biopsy. Information obtained from MD Anderson Cancer Center; NIH, additional studies such as karyotype, flow cytometry, and molecular genetics is usu- Grant/Award Number: CA016672 ally complementary and may help refine diagnosis. A new WHO classification of MDS was proposed in 2022. Under this classification, MDS is now termed myelodys- plastic neoplasms. Risk-stratification: Prognosis of patients with MDS can be calculated using a number of scoring systems. All these scoring systems include analysis of peripheral cytope- nias, percentage of blasts in the bone marrow, and cytogenetic characteristics. The most commonly accepted system is the Revised International Prognostic Scoring System (IPSS-R). Recently, genomic data has been incorporated resulting in the new IPSS-M classification. Risk-adapted therapy: Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts, cytogenetic and mutational profiles, comorbidities, potential for allogeneic stem cell transplantation (alloSCT), and prior exposure to hypomethy- lating agents (HMA). Goals of therapy are different in lower risk patients than in higher risk and in those with HMA failure. In lower risk, the goal is to decrease trans- fusion needs and transformation to higher risk disease or AML, as well as to improve survival. In higher risk, the goal is to prolong survival. In 2020, two agents were approved in the US for patients with MDS: luspatercept and oral decitabine/cedazur- idine. In addition, currently other available therapies include growth factors, lenalidomide, HMAs, intensive chemotherapy, and alloSCT. A number of phase 3 combinations studies have been completed or are ongoing at the time of this report. At the present time there are no approved interventions for patients with progressive or refractory disease particularly after HMA based therapy. In 2021, several reports indicated improved outcomes with alloSCT in MDS as well as early results from clinical trials using targeted intervention. Am J Hematol. 2023;98:1307–1325. wileyonlinelibrary.com/journal/ajh © 2023 Wiley Periodicals LLC. 1307  10968652, 2023, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ajh.26984, Wiley Online Library on [24/04/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 1308 GARCIA-MANERO 1 | D I S E A S E OV E R V I E W different from that of patients not previously treated with such an agent with similar IPSS and IPSS-R scoring systems.18,19 Myelodysplastic syndrome (MDS) comprises a very heterogeneous group of myeloid malignancies with very distinct natural histories.1 MDS occurs in 3–4 individuals per 105 in the US population.2 Preva- 2 | DI AGN OS I S lence increases with age. In individuals age 60 and above, prevalence is 7–35 per 105.2 Other series have reported higher rates.3 MDS The diagnosis of MDS is generally suspected based on the presence affects more frequently males than females.2 Exposure to prior chemo of cytopenia. Diagnosis is confirmed by performing a bone marrow or radiation therapy is a risk for the development of MDS. Work over aspiration and biopsy. Both procedures provide different information. the last two decades has demonstrated that MDS is an heterogenous The bone marrow aspirate allows for detailed evaluation of cellular group of malignancies arising from distorted hematopoietic stem cell morphology and evaluation of percent of blasts. The bone marrow function,4 inflammatory and innate immune deregulation,5 deregu- biopsy allows for determination of bone marrow cellularity and archi- lated apoptosis,6 and multiple genomic events.7 This combination of tecture. Diagnosis is established by the presence of dysplasia. A num- molecular alterations results anemia, increased risk of infections, ber of morphological classifications are in place. The most recent one 8 bleeding, and transformation to acute myelogenous leukemia (AML). being the 2022 WHO classification (Table 1).20 Under this classifica- A majority of patients with MDS will die from complications of MDS tion, MDS is now myelodysplastic neoplasm, acronym MDS. I believe without transforming to AML and therefore the need for unique treat- changing the name is a mistake as these disorders are clearly syndro- ment strategies for patients with MDS.8 Further adding importance to mic not just neoplasms. This is for instance demonstrated by its asso- this concept is the discovery of the relation between comorbidities ciations with comorbities.10 In addition, a parallel effort was proposed 9 10 and clonal hematopoiesis and MDS suggesting an interplay by the ICC.21 My opinion is that the percentage of blasts in MDS between MDS and the development of other conditions such as should be still considered up to 20%. Decreasing the percentage of cardiovascular disease.11 blasts to 10% because prognosis is similar when compared to patients MDS is usually suspected by the presence of cytopenia on a rou- with AML makes no scientific sense as prognosis does not equate tine analysis of peripheral blood. This prompts evaluation of bone diagnosis. Using this paradigm, we could describe all diseases, solid marrow cell morphology (aspirate) and cellularity (biopsy). A manual and liquid tumors, with a poor risk abnormality, that is, p53 mutation, count of bone marrow blasts is fundamental for risk assessment. with the same name just because prognosis is poor or we can target it Cytogenetic analysis helps in predicting risk and in selecting therapy. (i.e., IDH mutations in AML and glioblastoma). In addition, morphologi- Once this information is collected, MDS risk can be calculated. cally MDS is different than AML. Details of these classifications have Patients with MDS can be stratified according to several internation- been reviewed elsewhere. ally accepted scoring systems. The original IPSS12 and the modified A number of additional tests are needed to complete the labora- 13 IPSS-R are the most commonly used systems. These two systems tory evaluation of a patient with MDS. It is well established that cyto- are also important because they serve as part of the main eligibility genetic patterns are very heterogeneous in MDS.22 Cytogenetics are 14 criteria for past and ongoing registration clinical trials. Using IPSS and IPSS-R, patients with MDS are generally divided in two different broad subgroups: lower and higher risk disease. Patients with lower TABLE 1 The fifth edition of the WHO MDS classification.20 risk disease by IPSS are those with low and intermediate-1 disease and very, low and some subsets of intermediate risk by IPSS-R. MDS with defining genetic Patients with higher risk disease are those with intermediate-2 and abnormalities Blasts high risk by IPSS and some subsets of intermediate, high, and very MDS with low blasts and isolated 5q