Splenic irradiation prior to HCT to reduce relapse risk in patients with MF

Splenomegaly is a hallmark of myelofibrosis (MF) and is associated with poor outcomes including graft failure and poor graft functions at the time of hematopoietic cell transplant (HCT). JAK1/2 inhibitors are the clinically available treatment options for patients with splenomegaly. However, many patients are either not eligible or relapse after treatment with Janus kinase (JAK1)/2 inhibitors. Therefore, treating splenomegaly after HCT and JAK1/2 inhibitors is still an unmet need in MF.

During the 50th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Gagelmann presented results from a retrospective study investigating the efficacy of splenic irradiation before HCT in patients with MF.¹ We summarize this presentation below.

Study design¹

• This was a retrospective study of data from patients with primary or secondary MF, receiving splenic irradiation as a part of the HCT algorithm.
• Blood counts were collected before and after irradiation, at Day 50 and Day 100 after HCT.
• Primary outcomes were spleen size reduction and safety after irradiation.
• Other outcomes included:
  • neutrophil and platelet engraftment;
  • relapse incidence;
  • non-relapse mortality; and
  • overall survival.
• A matched-adjusted comparison was conducted after data collection using a propensity score matching immediate transplant and splenectomy.

Key findings

• Overall, 59 patients with a median age of 59 years were included
  • 71% were diagnosed with primary MF.
  • 75% were previously treated with ruxolitinib and 5% with fedratinib.
  • Approximately 40% of patients had a calreticulin mutation and >40% had a JAK2 mutation.
  • The median total irradiation dose was 7 Gy and the median time between HCT, and irradiation was 2 weeks.
• Spleen size, platelets, and leukocytes were significantly reduced after irradiation but before conditioning treatment (Figure 1).

Figure 1. Efficacy and safety variables pre- and post-irradiation* 

HCT, hematopoietic cell transplant.
*Adapted from Gagelmann, et al.¹

• After the transplant:

• • with a median of 18 days, the neutrophil engraftment was 92%;
  • with a median of 34 days, platelet engraftment was 81%; and
  • three patients developed veno-occlusive disease, two patients died within three months, and the third patient was successfully treated with defibrotide and is still alive.

• Dose intensity, portal vein thrombosis, MPN total symptom score, and high-intensity conditioning therapy impacted survival outcomes post-irradiation and HCT.
• In the matched adjusted comparison (Figure 2), overall survival and non-relapse mortality were similar among patients who underwent irradiation, immediate HCT, or splenectomy; however, splenic irradiation significantly reduced relapse incidence compared to immediate HCT and splenectomy (p = 0.01).

Figure 2. Matched adjusted comparison*

MTSS, MPN total symptom score.
*Adapted from Gagelmann, et al.¹