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AML ( including de novo and secondary ), and eight with relapsed / refractory AML .

Most of the patients had adverse-risk disease ( n = 14 ), and median IDH1 variant allele frequency at enrollment was 22.7 %.

Treatment consisted of 28-day cycles of ivosidenib 500 mg daily ( starting on day 14 ), combined with venetoclax with or without azacitidine at one of three dose levels ( DLs ):

TABLE . Outcomes According to Dose Levels

• DL1 : ivosidenib plus venetoclax 400 mg ( n = 6 )

• DL2 : ivosidenib plus venetoclax 800 mg ( n = 6 )

• DL3 : ivosidenib plus venetoclax 400 mg plus azacitidine 75 mg / m ² on days 1-7 ( n = 13 )

After a median follow-up of 16.1 months , the overall response rate was 92 %, including 67 % in DL1 and 100 % in DL2 and DL3 .

The rate of composite complete response ( CRc ; including CR with incomplete or complete hematologic recovery ) was 84 % ( TABLE ). Rates of CRc were highest in the DL2 and DL3 groups , and in patients with newly diagnosed AML or MDS .

Patients received a median of four treatment cycles , and responses were ongoing at one year in 62 % of patients ( 33 % with DL1 ; 50 % with DL2 ; and 82 % with DL3 ).

The rate of one-year overall survival ( OS ) was 68 % for the entire study population : 83 % in DL3 , 67 % in DL2 , and 50 % in DL1 . The authors added that rates of one-year OS were 71 % among patients with newly diagnosed AML , 50 % in relapsed / refractory AML , and 100 % in MDS . Of patients whose disease responded to treatment , 60 % achieved measurable residual disease ( MRD ) negativity , which correlated with improved OS ( median OS = not reached vs . 8.5 months ; p = 0.038 ).

The most common grade 3 / 4 adverse events included febrile neutropenia ( 28 %) and pneumonia ( 24 %). The investigators added that two patients experienced tumor lysis syndrome and four experienced differentiation syndrome , but that all cases resolved with medical management .

“ Ivosidenib plus venetoclax , with or without azacitidine , was associated with both an expected and tolerable safety profile and resulted in high composite complete response rates in both the doublet and triplet cohorts ,” Dr . Lachowiez stated in his presentation , adding that “ patients had durable responses across various disease groups .” The study is continuing to enroll patients and these initial results will need to be confirmed in larger studies .

Study authors report no relevant conflicts of interest .

Reference Lachowiez CA , Borthakur G , Loghavi S , et al . A phase Ib / II study of ivosidenib with venetoclax +/ - azacitidine in IDH1-mutated myeloid malignancies . Abstract # 7012 . Presented at the 2021 American Society of Clinical Oncology Annual Meeting , June 4-8 , 2021 .

Prophylactic treatment with letermovir improved overall survival ( OS ) and significantly decreased the incidence of clinically significant cytomegalovirus ( CMV ) infection in patients who underwent allogeneic hematopoietic cell transplantation ( alloHCT ), according to results from a single-center study presented at the 2021 ASCO Annual Meeting .

Lead author Delaney Wolfe , PharmD , of The Ohio State University Comprehensive Cancer Center , and colleagues also reported that patients who developed acute graft-versus-host disease ( GVHD ) showed significantly less CMV viremia , suggesting that these patients may benefit from continued letermovir prophylaxis beyond 100 days .

CMV is the most common infection seen in patients after alloHCT and is associated with increased mortality , the researchers explained . Human leukocyte antigen ( HLA ) mismatch , high-dose corticosteroids , and GVHD all contribute to the risk of CMV infection . Patients who experience GVHD have a further heightened risk of CMV infection due to the use of immunosuppressive therapies to treat GVHD .

In this single-center , retrospective study , investigators enrolled a total of 262 CMV-seropositive patients who underwent alloHCT between June 1 , 2016 , and June 30 , 2020 , to determine the effectiveness of extended letermovir in patients who develop GVHD .

A total of 119 patients had received letermovir prophylaxis , while 149 had not . Of the 111 patients who were treated for clinically significant CMV infection , 81 did not receive letermovir ( 57 %), compared with 29 patients who did ( 24 %).

Incidence of CMV viremia was significantly reduced in all patients who received letermovir ( hazard ratio [ HR ] = 0.21 ; p < 0.001 ), the authors reported ( TABLE ). After adjusting for age , gender , GVHD prophylaxis , and the use of antithymocyte globulin or T-cell – depleted graft , CMV viremia was also significantly reduced among patients who developed grade > 2 acute GVHD within 200 days of undergoing alloHCT ( HR = 0.12 ; p < 0.001 ).

Letermovir prophylaxis was associated with improved OS ( HR = 0.46 ; p = 0.04 ) and lower rates of non-relapse mortality ( HR = 0.41 ; p = 0.04 ), the researchers added .

The median duration of letermovir prophylaxis was 95 days , while nine patients continued letermovir therapy indefinitely for recurrent CMV viremia . While these results suggest a role for continued letermovir prophylaxis in transplant recipients , the findings from this single-center analysis may not be generalizable to other patient populations . Further studies are required to determine the effectiveness of letermovir prophylaxis past day 100 in patients who develop GVHD , the authors concluded .

This study is limited by changes in clinical practice over time that may have impacted the results and the investigators ’ inability to assess letermovir compliance . ●

The authors report no relevant conflicts of interest .

Reference Wolfe D , Zhao Q , Siegel EG , et al . Letermovir prophylaxis and cytomegalovirus reactivation in adult allogeneic hematopoietic cell transplant recipients with graft versus host disease . Abstract # 7004 . Presented at the 2021 American Society of Clinical Oncology Annual Meeting , June 4-8 , 2021 .

TABLE . Outcomes in Patients Treated With or Without Letermovir Prophylaxis

No Letermovir ( n = 143 )

Letermovir ( n = 119 ) p Value

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