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. 2022 Oct;101(10):2263-2270.
doi: 10.1007/s00277-022-04932-6. Epub 2022 Aug 23.

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia

A Luna  1 , L Pérez-Lamas  1 , C Boque  2 , P Giraldo  3 , B Xicoy  4 , C Ruiz Nuño  5 , M Moreno Vega  6 , A Alvarez-Larrán  7 , A Salamanca  8 , A García-Noblejas  9 , F Vall-Llovera  10 , L Villalon  11 , N De Las Heras  12 , E Ramila  13 , M Pérez-Encinas  14 , B Cuevas  15 , R Perez-Lopez  16 , F Sanchez-Guijo  17 , A Jiménez-Velasco  18 , S Lakhwani  19 , L Felipe Casado  20 , A Rosell  21 , A Escola  22 , M J Fernández  23 , C Garcia-Hernandez  24 , C Cervero  25 , E Mora  26 , M Sagüés  2 , S Suarez-Varela  8 , P Vélez  2 , P Carrascosa Mastell  27 , R F Bitaube  8 , L Serrano  27 , M Cortes  28 , J A Vera Goñi  29 , J L Steegmann  9 , V Gomez Garcia de Soria  9 , J M Alonso-Dominguez  30 , M Colorado Araujo  31 , A Paz Coll  32 , J C Hernandez-Boluda  33   34 , V García-Gutiérrez  35
Affiliations

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia

A Luna et al. Ann Hematol. 2022 Oct.

Abstract

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Keywords: Asciminib; Inhibitors; Leukemia.

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Conflict of interest statement

•L. Pérez-Lamas: Novartis: sponsored travel.

•V. García-Gutiérrez: Novartis: Speaker Honoraria, advisory committees. BMS, Incyte, Pfizer, CTA consultancy, honoraria, and research funding.

•F. Sanchez Guijo, Novartis, Celgene, Incyte, Pfizer, Takeda, Roche, Gilead, Amgen Consultancy, and horonaria.

•JM. Alonso-Dominguez: research funding from Incyte, Celgene, Pfizer, Astellas. BMS: Speaker Honoraria, advisory committees; Pfizer: Speaker Honoraria, advisory committees. Incyte: Advisory committees.

•S. Lakhwani: Novartis: Speaker honoraria, advisory committees; BMS: Speaker honoraria.

Figures

Fig. 1
Fig. 1
Adverse events in the entire asciminib cohort, stacked according to severity
Fig. 2
Fig. 2
Event-free survival considering prior ponatinib treatment. Event was defined as: on-treatment death, progression to advanced phase, confirmed loss of complete cytogenetic response (CCyR), loss of complete hematologic response (CHR), treatment discontinuation for any reason (intolerance or lack of efficacy), or death for any reason
Fig. 3
Fig. 3
Reasons for asciminib discontinuation at the end of follow-up, considering prior ponatinib use
See this image and copyright information in PMC

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