Impact of Comorbidities In Patients with Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) Treated with Azacitidine (AZA)

Comorbidity in older patients with AML or high risk MDS is frequent, and usually affects the therapeutic decision making. The hematopoietic cell transplantation specific comorbidity index (HCTCI) developed by Sorror et al, is widely used in predicting post-transplantation outcome in patients with AML and MDS. Recently, the HCTCI showed prognostic impact in a cohort of patients with high risk MDS treated only with supportive care. AZA have shown clinical efficacy in elderly patients with high risk MDS. However, it is not clear if AZA is safe and effective in patients with comorbidities.

To study the impact of comorbidity, determined by the HCTCI, in a retrospective cohort of patients with MDS or AML treated with AZA

Between October 2007 and July 2010, 30 patients diagnosed with MDS or AML received AZA 75 mg/m2 /d × 7d/4 weeks, or less intensive schedules (7d/4w n=2, 5d/4 weeks n= 12, 5-2-2 n= 16).

Median age was 71 years (range 44–88), 16M/14F. Regarding HCTCI, 17 patients were classified in low-intermediate risk, score 0–2, and 13 patients in high risk (score ≥ 3). Patients with HCTCI of 0–2 were classified as: 8 patients with MDS (High/ Int2 MDS n= 4, Intermediate-1 MDS n= 4), 8 patients with AML in first relapse after intensive chemotherapy (IC) or stem cell transplantation (SCT) and <20% of marrow blasts, and 1 patient with AML with MDS related changes. The group of patients with HCTCI ≥3 included: 7 MDS (high/int2 MDS n=5, secondary MDS n=1, Int-1 MDS n =1), 6 AML (AML with MDS related changes n= 3, AML in relapse after IC or SCT and <20% blasts n=3).

Response to treatment was estimated according to the International Working Group.

The median number of cycles of AZA was 7 (1-26); 5 cycles in the HCTCI of score 0–2 and 7 cycles in the HCTCI>= 3.

There were three patients who received only 1 cycle due to progression (n=1) and early death, caused by infection (n=2). Both patients showed neutropenia before starting AZA, one showed HCTCI of low risk.

Responses were evaluated when 3 or more cycles were administered. Overall response rate (ORR) was 48% (14/27), with 13% complete response (CR). In the group of patients with HCTCI of 0–2, ORR was 40% (6/15) including 2 CR, 1 marrow CR, 2 partial response (PR), and 1 patient with haematological improvement (HI). Median overall survival (OS) for responders with low risk by HCTCI was 18 months (4-28). Transformation to AML was seen in two responding patients, after 16 and 18 months. Allo SCT was performed in one patient.

Regarding patients with HCTCI ≥3, ORR was 66% (8/12), including 2 CR, 2 PR, 4 HI, 3 of them with transfusion independence. Median OS for responders was 11 months (range 5–33 months). Transformation to AML was seen in a patient after 23 months of treatment, and relapse with 10% of blasts was observed in a patient with CR after six months of AZA.

Grade 3–4 toxicity according to WHO was observed in 5 patients, 3 of them with HCTCI low (1 bleeding event, 4 respiratory tract infections). One patient with HCTCI ≥3 died after 8 months of HI, because no treatment-related event. One patient with HI and HCTCI≥3 did not continued AZA after 5 cycles because frequent respiratory tract infections.

In this preliminary cohort, AZA was well tolerated and active in patients with HCTCI≥3. The response rate was in accordance with results observed with a similar cohort of patients without significant comorbidities. These results might be confirmed with larger number of patients in further studies.

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