Treatment Approach for MDS with Residual Dysplasia After 1 Year of Azacitidine-Venetoclax
Proceed to allogeneic hematopoietic cell transplantation (allo-HCT) evaluation immediately, as this patient has achieved cytogenetic normalization (46,XX karyotype) but retains residual trilineage dysplasia after 1 year of therapy—representing an optimal window for transplant with reduced disease burden. 1
Rationale for Transplant Evaluation
The NCCN 2025 MDS guidelines explicitly recommend allo-HCT for patients who achieve response to hypomethylating agents (HMAs) with or without venetoclax, particularly when blast counts are controlled. 1 Your patient has achieved cytogenetic response (normal karyotype) which represents meaningful disease control.
Most transplant centers require evidence of response to HMAs before proceeding to allo-HCT when baseline blasts are >10%. 1 The normalization of karyotype from presumably abnormal baseline constitutes such a response.
Continuing azacitidine-venetoclax as maintenance therapy while arranging transplant logistics is appropriate, as patients with clinical benefit should continue HMA treatment. 1
Critical Decision Points
If Transplant-Eligible:
- Early referral for transplant evaluation is recommended to allow efficient transition to transplant. 1
- Continue azacitidine-venetoclax as bridging therapy until transplant, as the regimen has demonstrated disease control evidenced by cytogenetic normalization. 1
- Pre-transplant debulking to reduce marrow blasts to <5% is recommended to reduce post-transplant relapse risk. 1
If Transplant-Ineligible or Patient Declines:
- Continue azacitidine-venetoclax indefinitely as maintenance therapy since the patient has achieved clinical benefit (cytogenetic response). 1
- Re-evaluation with bone marrow and/or molecular testing is recommended to monitor for progression. 1
Monitoring Strategy During Continued Therapy
- Perform bone marrow re-evaluation periodically to assess blast percentage and dysplasia progression. 1
- Monitor for treatment failure, defined as loss of response or disease progression, which would trigger consideration of alternative therapies. 1
- If IDH1 mutation is present and not previously tested, ivosidenib or olutasidenib may be considered if progression occurs. 1
Common Pitfalls to Avoid
- Do not discontinue azacitidine-venetoclax simply because residual dysplasia persists—morphologic dysplasia can remain despite cytogenetic response and does not necessarily indicate treatment failure. 1
- Do not delay transplant evaluation waiting for complete morphologic remission—cytogenetic normalization represents sufficient response to proceed. 1
- Do not assume treatment failure based solely on persistent dysplasia without evidence of increasing blasts or cytogenetic relapse. 1
Alternative Considerations if Disease Progresses
- For patients with mIDH1 mutations: single-agent ivosidenib, olutasidenib, or azacitidine combined with olutasidenib followed by allo-HCT. 1
- Enrollment in clinical trials is recommended for patients without actionable mutations who progress. 1
- High-intensity chemotherapy may be considered as bridge to transplant in select cases. 1