Fludarabine-busulfan regimen confers favorable long-term outcomes in myelofibrosis
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Myeloablative fludarabine and busulfan conditioning appeared effective for patients with myelofibrosis undergoing allogeneic stem cell transplant, according to results presented at Society of Hematologic Oncology Annual Meeting.
The regimen conferred favorable long-term outcomes, and researchers identified several factors associated with OS.
“The optimal conditioning regimen for myelofibrosis, particularly [for] older patients undergoing allogeneic stem cell transplant, needs to be defined,” Jacinth Joseph, MD, a physician in the Stem Cell Transplantation and Cellular Therapy Center at The University of Texas MD Anderson Cancer Center, said during a presentation. “Intensifying the busulfan-fludarabine regimen using pharmacokinetic monitoring appears to be promising [for] reducing relapse without increasing nonrelapse mortality.”
Multiple scoring systems can help predict outcomes for patients with myelofibrosis, both at diagnosis and the time of allogeneic transplant. Factors previously determined to predict poor prognosis include spleen size of 22 cm or greater, severe marrow fibrosis, receipt of more than 20 red cell transfusions, low hemoglobin, disease progression or lack of clinical improvement on JAK inhibitor therapy, and matched-unrelated donor transplant compared with matched-related donor transplant.
Joseph and colleagues aimed to report long-term outcomes after allogeneic stem cell transplant for patients with primary or secondary myelofibrosis who received a myeloablative busulfan-fludarabine regimen, and to assess the impact of prognostic factors on transplant outcomes.
The analysis included 65 consecutive patients (median age, 61 years; range, 27-73; 52% women) who received a uniform myeloablative conditioning regimen at MD Anderson Cancer Center between August 2007 and September 2019.
The majority of patients had Karnofsky performance score of 90 or 100 (76%) and favorable karyotype per mutation-enhanced International Prognostic Scoring System for transplant-age patients (78%). Most patients had received one (54%) or two (22%) prior lines of treatment, and had not received JAK2 inhibitors (51%).
Conditioning consisted of fludarabine dosed at 40 mg/m2 via IV daily for 4 days, and busulfan via IV dosed in a pharmacokinetic-guided manner to an average daily area under the curve (AUC) of 4,000 µmol/min or a total course AUC of 16,000 µmol/min.
Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate, as well as rabbit-antithymocyte globulin for patients who received transplant from unrelated donors.
Median follow-up for survivors was 36 months.
Researchers reported OS rates of 78% (95% CI, 65-86) at 1 year and 65% (51-76) at 3 years, nonrelapse mortality rates of 16% (95% CI, 8-26) at 1 year and 20% (95% CI, 11-30) at 3 years, and cumulative incidence of relapse of 21% (95% CI, 12-31) at 1 year and 27% (95% CI, 16-39) at 3 years.
Researchers identified several factors associated with shorter OS. These included time from diagnosis to transplant (>12 months vs. 12 months, HR = 3.01; 95% CI, 1.05-8.6), Hematopoietic Cell Transplantation-specific Comorbidity Index (3 vs. 0-2, HR = 3.41; 95% CI, 1.26-9.23), donor type (mismatched-unrelated vs. matched-related, HR = 7.16; 95% CI, 1.77-28.96), peripheral blasts (1 vs. 0, HR = 2.83; 95% CI, 1.07-7.48) and splenectomy prior to transplant (yes vs. no, HR = 3.69, 95% CI, 1.17-11.64).
Variables significantly associated with nonrelapse mortality included Hematopoietic Cell Transplantation-specific Comorbidity Index (3 vs. 0-2, HR = 10.09; 95% CI, 2.09-48.76) and donor type (mismatched-unrelated vs. matched-related, HR = 10.73; 95% CI, 1.05-109.4; matched-unrelated vs. matched-related, HR = 5.38; 95% CI, 1.14-25.3).
Splenectomy appeared significantly associated with cumulative incidence of relapse (yes vs. no, HR = 12.5; 95% CI, 4.75-32.88).
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Joseph J, et al. Abstract MPN-188. Presented at: Society of Hematologic Oncology Annual Meeting (virtual meeting); Sept. 9-12, 2020.
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