Observation as a Treatment Option in DDX41 mutated AML: A Case Report
Introduction/Background/Significance: Mutation of DDX41 (Dead/H-box helicase) gene, located on Chromosome 5q35.3, is seen in 1-2% of MDS/AML cases and demonstrates higher overall survival [1]. We report a case of observation in DDX41 mutated AML in a patient with favorable platelet and hemoglobin counts as opposed to standard of care, which typically includes hypomethylating agents (HMA) and/or Venetoclax or allogeneic hematopoietic stem cell transplant (alloHCT).
Materials and Methods/Case Presentation/Objective: A 75-year-old male with a past medical history of prostate cancer, status post radical prostatectomy 14 years prior, developed pancytopenia over the course of six months, with a gradual decline in blood counts. The patient denied fever, chills, weight loss, loss of appetite, night sweats, cough, abdominal pain, or abnormal bleeding. Family history was significant for prostate cancer in brother and rectal cancer in sister. Laboratory studies showed: WBC 2.1 × 109/L, ANC 800/μL, hemoglobin 12.4 g/dL, MCV 101.4 fL, and platelet count 96 × 109/L. Bone marrow biopsy revealed variably cellular marrow (5–40% cellularity) with increased CD34+ blasts (25% of marrow cellularity), consistent with AML. Cytogenetics and AML FISH were within normal limits. Next-generation sequencing identified germline DDX41 and CUX1 mutations. After a shared decision-making discussion, the patient opted for observation with regular laboratory monitoring (at least every two weeks) before initiating treatment such as HMA ± Venetoclax, if disease progression was observed. AlloHCT was not pursued due to patient preference and an unfavorable risk-benefit profile in this case.
Results/Description/Main Outcome Measures: In a retrospective study including 40 patients, 13 patients (32%) were observed with a significant five-year overall survival of 100% in the observation group compared to treatment group along with an improved median time to progression and median treatment free survival[1]. Recent studies have shown that treatment options such as alloHCT is associated with inferior survival and trended towards higher rate of mortality in DDX41 AML[2]. This case report paves way for future clinical trials exploring the option of observation as a potential management strategy in select patients with DDX41 mutation, especially those of advanced age or with comorbidities who may not be suitable candidates for alloHCT. Close monitoring with frequent lab checks can allow timely intervention with treatment options such as HMA, Venetoclax, or alloHCT if disease progression occurs.
Conclusions: This case report highlights observation as a potential management approach for patients with DDX41-mutated AML who have favorable blood counts, until disease progression, given that conventional treatment options have been associated with increased mortality and toxicity.
References
1. Al-Kali, A., et al., Observation and treatment in DDX41-mutated acute myeloid leukemia and myelodysplastic syndrome. Blood Cancer J, 2023. 13(1): p. 49. 2. Baranwal, A., et al., Outcomes of allogeneic transplant in patients with DDX41 mutated myelodysplastic syndrome and acute myeloid leukemia. Bone Marrow Transplant, 2022. 57(11): p. 1716-1718.
