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).

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).

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

Key learnings

Splenic irradiation reduced spleen size immediately after irradiation and OS and NRM were comparable to non-irradiated patients. The incidence of relapse was lower in patients who underwent splenic irradiation compared to those who underwent immediate HCT and those who received splenectomy. Severe thrombocytopenia, anemia, higher MPN total symptom score, portal vein thrombosis, and high-intensity conditioning therapy before HCT were independent predictors of the worse outcomes in patients with MF who received splenic irradiation. Overall, enlarged spleen reduction therapy is advised before splenic irradiation in this patient population.