Blast reduction strategies for patients with accelerated/blast-phase myeloproliferative neoplasms

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only therapy that offers long term survival for accelerated-phase (AC) and blast-phase (BP) myeloproliferative neoplasms (MPN). Currently, the use of acute myeloid leukemia based intensive/non-intensive blast reduction regimens and management considerations in patients with AC and BP is not well understood.

Recently, Davidson et al.¹ published a retrospective study in Blood Advances to evaluate the clinical outcomes of acute myeloid leukemia based blast reduction strategies in patients with AC/BP MPN. We summarize the key points below.

Study design¹

• In total, 138 patients were enrolled and given either:

• • Intensive therapies (n = 81): daunorubicin, high-dose cytarabine, fludarabine, idarubicin, granulocyte-colony stimulating factor, mitoxantrone, and etoposide + cytarabine
  • Non-intensive therapies (n = 57): hypomethylating agent monotherapy (HMA), azacitidine, decitabine, and venetoclax

• Primary endpoint was overall best response, measured as complete remission/complete remission with incomplete hematologic recovery or chronic phase MPN
• Patients were assessed for a median follow-up of 40.3 months

Key findings¹

• The overall best response rate was 77% for intensive and 39% for non-intensive regimens.
• More patients responded after HMA plus azacitadine and venetoclax treatment vs HMA alone (50% vs 33%, respectively).
• There were no statistically significant differences in median time to allo-HSCT in intensive vs non-intensive and type of regimen.
• The percentage of patients who achieved eligibility for allo-HSCT for each treatment regimen are provided in Figure 1.

Allo-HSCT, allogeneic hematopoietic stem cell transplantation; Ara-C, cytarabine; Aza, azacitidine; HD, high-dose; HMA, hypomethylating agent; Ven, venetoclax.
*Adapted from Davidson et al.¹

• Mutational burden remained high despite blast reduction posttreatment.
• No clear association between molecular response and treatment response.
• Full mutational clearance was only observed in patients who underwent successful allo-HSCT.

Key learnings
Both intensive and non-intensive regimens can be used as a bridge to allo-HSCT in selected patients. Responses to blast reduction strategies often entail a reversion to chronic phase MPN. Both blast-reduction strategies have limited disease modifying activity and allo-HSCT is therefore required for long-term disease control.