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Abstract: EP1082

Type: E-Poster Presentation

Session title: Myeloproliferative neoplasms - Clinical

Background

Accelerated phase (AP) and/or blast phase (BP) of BCR-ABL negative myeloproliferative

neoplasms (MPN) are associated with poor outcomes. Comparative efficacy of AML-type

induction regimens versus non-intensive hypomethylating agent (HMA)-based regimens is not

well studied. Further, the lack of standardized response criteria to evaluate the treatment of MPN-AP/

BP poses challenges in understanding treatment efficacy between various studies.

Aims

To determine the efficacy of intensive and non-intensive blast-reduction therapy in patients

with MPN-AP/BP using uniformly applied study-defined response criteria.

Methods

All patients with MPN-AP/BP assessed at Princess Margaret Hospital between 01/1998 and

12/2020 were identified from the program database. Only patients treated with intensive

induction chemotherapy and non-intensive azacytidine (AZA)-based therapy were included.

Intensive treatment included 3+7 (daunorubicin 60 mg/m² IV day (d) 1-3; AraC 100-200

mg/m² d1-7), FLAG-IDA (fludarabine 30 mg/m² IV & AraC 2000 mg/m² IV day 1-5; idarubicin 10

mg/m² IV d1-3; granulocyte-colony stimulating agent SC d1-6), or NOVE-HiDAC (mitoxantrone

10 mg/m² IV & etoposide 100 mg/m² d1-5; AraC 1000-1500 mg/m² every 12 hours for d1-2).

Non-intensive therapy consisted of AZA or AZA with venetoclax (AV). Targeted sequencing with

a myeloid gene panel was performed. The primary endpoint was overall survival (OS) (time of

AP/BP transformation until death or last follow-up), and overall response (CR, CRi or reversion

back to chronic phase of MPN), using study-defined criteria.

Results

All patients (n=124) with MPN-AP (n=27) and MPN-BP (n=97) treated with intensive

chemotherapy (3+7 [n=31]; FLAG-IDA/NOVE-HiDAC [n=46]) or non-intensive therapy (AZA

[n=36] AV [n=11]) were included. The proportion of patients >70 years old, with ECOG ≥2,

adverse ELN risk, and AP was higher in the non-intensive group. In evaluable patients, higher overall response rates were observed in patients treated intensively (78% [60/77] vs 38% [17/45], p<0.001). There was a trend towards improved response with AV (55% [6/11]) over AZA (32% [11/34]). Similar

response rates were observed in patients receiving upfront 3+7 (74% [23/31]) or FLAG-IDA/

NOVE-HiDAC (80% [37/46], p=0.58). However, patients receiving upfront 3+7 required

more second inductions (29% [9/31] vs 9% [4/46], p=0.03). No difference in HCT rates was

observed between induction regimens (43% [9/21] in 3+7 vs  58% [21/36] in FLAG-IDA/NOVE-HiDAC,

p=0.4). The median OS for the cohort was 9.7 months (95% CI 8.4-12). There was no

difference in OS between the intensive and non-intensive groups (HR 1.13 [95% CI 0.75-1.72].

OS was improved among patients receiving HCT (HR 0.3 [95%CI 0.17-0.54]). Factors

significantly associated with shorter OS in multivariable analysis included non-response, BP (vs

AP), number of mutated genes, and TP53 mutation. Factors negatively associated with

response in multivariable analysis were non-intensive therapy and TP53 mutation.

Conclusion

In this observational study, more rapid responses were observed with higher dose AraC

containing regimens FLAG-IDA or NOVE-HIDAC compared to 3+7 in MPN-AP/BP. Azacytidine

and venetoclax combination therapy appear to have higher response rate in comparison to

azacytidine alone, and merit prospective investigation.

Keyword(s): Azacitidine, Induction chemotherapy, Myeloproliferative disorder, Transformation