Advanced Systemic Mastocytosis with associated haematological neoplasm: Treatment with avapritinib can facilitate successful bridge to allogeneic haematopoietic cell transplant

Sriskandarajah, Priya; McLornan, Donal; Oni, Clare; Wilson, Alfred J.; Woodley, Cheryl M.; Ciesielska, Monika; Raj, Kavita; Dillon, Richard; Ethell, Mark; Chacko, Joseph; Orchard, Kim; Radia, D. H.

doi:10.1016/j.retram.2023.103398

Cited by 5 publications

(5 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to AML [ 36 – 38 ] or ALL [ 39 ], response of the SM and/or the AHN compartment to treatment prior alloHCT significantly prolonged transplant-associated OS. Our data also show that for patients with resistant or progressive disease before alloHCT, this procedure might not be a reasonable rescue option as the graft-versus-AdvSM effect does not seem to be sufficiently effective in patients with high disease burden, a phenomenon known from other myeloid neoplasms [ 40 – 42 ]. To optimize outcome in AdvSM, transplant eligible patients should therefore be transplanted at time of best response to pre-allo treatment; hence, close interdisciplinary cooperation between mastocytosis and transplant centers is warranted to define these time points.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis: A retrospective analysis of the DRST and GREM registries

Lübke,

Christen,

Schwaab

et al. 2024

Leukemia

View full text Add to dashboard Cite

We identified 71 patients with AdvSM (aggressive SM [ASM], SM with an associated hematologic neoplasm [SM-AHN, e.g., acute myeloid leukemia, SM-AML], mast cell leukemia [MCL]) in two national registries (DRST/GREM) who received an allogeneic hematopoietic cell transplantation (alloHCT) performed in Germany from 1999–2021. Median overall survival (OS) of ASM/SM-AHN (n = 30, 45%), SM-AML (n = 28, 39%) and MCL ± AHN (n = 13, 19%) was 9.0, 3.3 and 0.9 years (P = 0.007). Improved median OS was associated with response of SM (17/41, 41%; HR 0.4 [0.2–0.9], P = 0.035) and/or of AHN (26/43, 60%, HR 0.3 [0.1–0.7], P = 0.004) prior to alloHCT. Adverse predictors for OS included absence of KIT D816V (10/61, 16%, HR 2.9 [1.2–6.5], P < 0.001) and a complex karyotype (9/60, 15%, HR 4.2 [1.8–10.0], P = 0.016). HLA-match, conditioning type or transplantation at centers reporting above-average alloHCTs (≥7) had no impact on OS. Taking into account competing events at years 1, 3 and 5, relapse-related mortality and non-relapse mortality rate were 15%/23%, 20%/30% and 23%/35%, respectively. Irrespective of subtype, subsequent treatment response was achieved in 13/30 (43%) patients and was highest on midostaurin/avapritinib (7/9, 78%). We conclude that outcome of alloHCT in AdvSM is more affected by disease phenotype and treatment response prior to transplant than by transplant characteristics.

show abstract

Section: Discussionmentioning

confidence: 99%

Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis: A retrospective analysis of the DRST and GREM registries

Lübke,

Christen,

Schwaab

et al. 2024

Leukemia

View full text Add to dashboard Cite

show abstract

“…In such cases, the AHN portion of the disease may or may not respond to these standard treatments in the same way as in patients without SM [54][55][56]. Midostaurin and avapritinib may also be effective in these cases, especially when most or all AHN cells are KIT mutated, or are driven by KIT-induced oncogenic pathways [57,58]. However, in SM-AML, some or even most AML-subclones may lack KIT D816V [51,52].…”

Section: Special Considerations For the Treatment Of Patients With Sm...mentioning

confidence: 99%

“…As mentioned, when both the SM and the AHN require specific anti-neoplastic therapies, drug combinations have to be considered. In patients with an aggressive malignancy, such as MCL and/or AML, intensive therapy (plus TKI therapy) is introduced to achieve remission before the patient is prepared for allogeneic HSCT [1,2,[45][46][47]58]. In those who are not eligible for HSCT, continuous treatment with avapritinib may be an alternative treatment option.…”

Section: Special Considerations For the Treatment Of Patients With Sm...mentioning

confidence: 99%

“…HSCT remains the only potentially curative treatment for patients with advanced SM who are resistant against multiple drug therapies. Especially young and fit patients with multi-resistant advanced SM may benefit from HSCT [44][45][46]56,58,[61][62][63][64]. In these patients, graft versus mastocytosis effects have been documented [44,62,63].…”

Section: Allogeneic Hsctmentioning

confidence: 99%

“…The type of debulking therapy depends on the type of AHN, the presence of KIT D816V, and other molecular targets displayed by neoplastic cells. In those with a high variant allele frequency of KIT D816V, avapritinib may be appropriate and sufficient to induce debulking [58]. In the case of SM-AML, poly-chemotherapy should be considered as the most effective and most promising approach to achieve substantial debulking before HSCT.…”

Section: Allogeneic Hsctmentioning

confidence: 99%

See 2 more Smart Citations

Antibody-Based and Cell Therapies for Advanced Mastocytosis: Established and Novel Concepts

Valent,

Akin,

Arock

et al. 2023

IJMS

View full text Add to dashboard Cite

Advanced systemic mastocytosis (SM) is a heterogeneous group of myeloid neoplasms characterized by an uncontrolled expansion of mast cells (MC) in one or more internal organs, SM-induced tissue damage, and poor prognosis. Advanced SM can be categorized into aggressive SM (ASM), MC leukemia (MCL), and SM with an associated hematologic neoplasm (SM–AHN). In a vast majority of all patients, neoplastic cells display a KIT mutation, mostly D816V and rarely other KIT variants. Additional mutations in other target genes, such as SRSF2, ASXL1, or RUNX1, may also be identified, especially when an AHN is present. During the past 10 years, improved treatment approaches have led to a better quality of life and survival in patients with advanced SM. However, despite the availability of novel potent inhibitors of KIT D816V, not all patients enter remission and others relapse, often with a multi-mutated and sometimes KIT D816V-negative disease exhibiting multi-drug resistance. For these patients, (poly)chemotherapy, antibody-based therapies, and allogeneic hematopoietic stem cell transplantation may be viable treatment alternatives. In this article, we discuss treatment options for patients with drug-resistant advanced SM, including novel KIT-targeting drugs, antibody-based drugs, and stem cell-eradicating therapies.

show abstract

Allogeneic haematopoietic cell transplantation for advanced systemic mastocytosis: Best practice recommendations on behalf of the EBMT Practice Harmonisation and Guidelines Committee

McLornan,

Czerw,

Damaj

et al. 2024

Leukemia

View full text Add to dashboard Cite

Advanced Systemic Mastocytosis with associated haematological neoplasm: Treatment with avapritinib can facilitate successful bridge to allogeneic haematopoietic cell transplant

Cited by 5 publications

References 11 publications

Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis: A retrospective analysis of the DRST and GREM registries

Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis: A retrospective analysis of the DRST and GREM registries

Antibody-Based and Cell Therapies for Advanced Mastocytosis: Established and Novel Concepts

Allogeneic haematopoietic cell transplantation for advanced systemic mastocytosis: Best practice recommendations on behalf of the EBMT Practice Harmonisation and Guidelines Committee

Contact Info

Product

Resources

About