HSCT Leads to Long-Term Survival for MDS After Conditioning

Hematopoietic stem cell transplantation (HSCT) yields long-term overall survival (OS) outcomes irrespective of the conditioning regimen for patients with myelodysplastic syndromes (MDS), according to a long-term follow-up of the phase III RICMAC study.

The prospective, multicenter, open-label study led by Christian Niederwieser, MD, investigated HSCT outcomes after two conditioning types: myeloablative conditioning (MAC) and reduced intensity conditioning (RIC).

Patients were randomized to receive either MAC (n=64) with busulfan and cyclophosphamide or RIC (n=65) with busulfan and fludarabine followed by HSCT.

The primary endpoints were OS and regression-free survival (RFS). Secondary endpoints included relapse-free survival (RFS), relapse incidence (RI), non-relapse mortality (NRM), and chronic graft-versus-host disease (cGVHD) incidence.

After a median follow-up of 6.2 years, the 10-year OS was 54.0% (CI, 95%; 38.5–69.4) for RIC and 44.4% for MAC (CI, 95%; 29.3–59.5). The 10-year RFS was 43.9% (CI, 95%; 29.1–58.8) for RIC and 44.2% (CI, 95%; 29.9–58.6) for MAC (P= .78). The NRM was comparable across both arms (30.5% after MAC vs 30.3% after RIC; P=.50).

In a multivariate analysis, those with low cytogenetic risk had better OS (P=.002), RFS (P=.02), and NRM (P=.015) after RIC compared with MAC. Independent risk factors for OS and RFS included Eastern Cooperative Oncology Group status and chemotherapy prior to HSCT.

The 10-year cumulative RI was 25.2% (CI, 95%; 12.3–38.2) after MAC and 25.7% (CI, 95%; 13.5–38.0) after RIC (P= .66). Chemotherapy administration before HSCT was also associated with a higher RI (HR, 3.02; CI, 95%; 1.37–6.64; P=.006).

The incidence of cGVHD was comparable across treatment groups (68.2% for MAC vs 65.5% for RIC; P=.70). Seventy patients in total developed cGVHD by a median of six months.

Six patients (four after RIC and two after MAC) died after the first report. Eight new patients (four in each arm) relapsed, totaling 28 relapses for the whole analysis.

“Overall, we report that low-risk cytogenetic patients have the highest benefit with RIC for OS and RFS because of lower NRM,” the researchers concluded. “Therefore, RIC may be considered as equivalent to MAC in younger patients with MDS, but preferentially cytogenetic low-risk patients should be treated with RIC.”

Reference

Niederwieser C, Iacobelli S, Franke GN, et al. Reduced intensity versus myeloablative conditioning for MDS: long-term results of an EBMT phase III study (RICMAC). 2024. Bone Marrow Transplant. doi:10.1038/s41409-024-02282-7