ORLANDO, Fla.Combination cytokine immunotherapy is well tolerated and effective in patients with aplastic anemia and has activity in a subset of patients with myelodysplastic syndrome (MDS), updated results of a phase 2 study concluded.

While responses with the combination—rabbit antithymocyte globulin (rATG), cyclosporine, steroids, and G-CSF—were slow to occur, they were durable and associated with improved survival, Tapan Kadia, MD, of MD Anderson Cancer Center, Houston, Texas, and colleagues reported. Rate of serious infections was relatively low. However, infusion reactions were common and should be managed with premedication and supportive care, the investigators noted in a poster presentation at the 52nd American Society of Hematology Annual Meeting and Exposition. HLA-DR15 positivity was found to correlate with response in patients with aplastic anemia, but not in MDS.

In patients with aplastic anemia and an International Prognostic Scoring System score of low or intermediate-1 risk MDS, the single-arm phase 2 study evaluated efficacy and safety of rATG 3.5 mg/kg/day (or 2.5 mg/kg/day for age ≥55 years) intravenously (IV) for 5 days, methylprednisone 1 mg/kg/day IV daily for 5 days (given prior to each dose of ATG), followed by oral prednisone tapered off over 1 month, G-CSF (filgrastim daily or pegfilgrastim every 2 weeks) subcutaneously for up to 3 months, and cyclosporine (5 mg/kg) daily for up to 6 months. Dose reductions or interruptions for toxicities were allowed at the discretion of the treating physician. Responses were assessed 3 months after initiation of therapy.

Of 51 patients enrolled, 46 have received treatment, 23 (50%) with aplastic anemia and 23 (50%) with MDS. Median age was 60 years (range, 19-82 years) overall and 54 years (range, 19-82 years) in patients with aplastic anemia, and 63 years (range, 48-79 years) in the MDS cohort. Forty-three patients were evaluable for response, 21 with aplastic anemia and 22 with MDS. Of those with aplastic anemia, 13 (62%) responded (4 CR, 8 PR, 1 HI); and, with MDS, 6 (27%) responded (2 CR, 4 HI). Median age of responders was 59 years (range, 19-79 years). Median time to response was 3.2 months.

Of 46 pts who received treatment, 20 (43%) were HLA-DR15 positive, 22 (48%) were negative, and 4 (9%) were not checked. In the MDS cohort, 9 patients (39%) were HLA-DR15 positive and none responded. In the aplastic anemia cohort, 11 (48%) were HLA-DR15 positive, out of which 6 (55%) responded. Among these 19 responding patients, 6 (32%) were HLA-DR15 positive and all had aplastic anemia. Median disease-free survival for responders (CR & PR) was 26 months. Median overall survival of responders has not been reached, compared with 20 months for nonresponders (P<0.001).

Overall, treatment was tolerable. The most common grade 3/4 toxicities reported were thrombocytopenia (43%), neutropenia (41%), transaminase elevation (13%), hyperbilirubinemia (7%), infection/fever (7%), and hyperglycemia (4%). Grade 3/4 dyspnea, abdominal pain, and hypertension occurred in 1 patient each. Twenty patients (43%) had infusion-related reactions that included fever, chills, and dyspnea; all were manageable with supportive care.