Ponatinib vs. Imatinib as Frontline Treatment for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia : A Matching Adjusted Indirect Comparison
Ribera, Jose-Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Prawitz, Thibaud (Evidera Inc)
Freitag, Andreas (Evidera Inc)
Sharma, Anuj (Evidera Inc)
Dobi, Balázs (Evidera Inc)
Rizzo, Federica (Incyte Biosciences International Sàrl, Morges, Switzerland)
Sabatelli, Lorenzo (Incyte Biosciences International Sàrl, Morges, Switzerland)
Patos, Petros (Incyte Biosciences International Sàrl, Morges, Switzerland)

Date:	2023
Abstract:	Introduction: Efficacy of ponatinib-based treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) has not been compared to imatinib-based treatments in head-to-head clinical trials. We evaluated its efficacy versus imatinib-based regimens using a matching adjusted indirect comparison. Methods: Two ponatinib studies were used: the phase 2 MDACC study of ponatinib + hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) in adult patients and the phase 2 GIMEMA LAL1811 study of ponatinib + steroids in patients > 60 years/unfit for intensive chemotherapy and stem cell transplant. Studies on imatinib as first-line treatment in adults with Ph + ALL were identified using a systematic literature search. Population adjustment was based on the prognostic factors and effect modifiers identified by clinical experts. Hazard ratios (HRs) were calculated for overall survival (OS) and odds ratios (ORs) for complete molecular response (CMR). Results: The systematic literature search identified two studies (GRAAPH-2005 and NCT00038610) reporting the efficacy of first-line imatinib + hyper-CVAD and one study reporting the efficacy of first-line imatinib monotherapy induction + imatinib-based consolidation (CSI57ADE10). Ponatinib + hyper-CVAD prolonged OS and gave a higher CMR rate than imatinib + hyper-CVAD. The adjusted HR [95% confidence interval (CI)] for OS was 0. 35 (0. 17-0. 74) for MDACC vs. GRAAPH-2005 and 0. 35 (0. 18-0. 70) for MDACC vs. NCT00038610; the adjusted OR (95% CI) for CMR was 12. 11 (3. 77-38. 87) for MDACC vs. GRAAPH-2005 and 5. 65 (2. 02-15. 76) for MDACC vs. NCT00038610. Ponatinib + steroids prolonged OS and gave a higher CMR rate than imatinib monotherapy induction + imatinib-containing consolidation. The adjusted HR (95% CI) for OS was 0. 24 (0. 09-0. 64) and the adjusted OR (95% CI) for CMR was 6. 20 (1. 60-24. 00) for GIMEMA LAL1811 vs. CSI57ADE10. Conclusion: In adults with newly diagnosed Ph + ALL, first-line treatment with ponatinib was associated with better outcomes than first-line treatment with imatinib.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Acute lymphoblastic leukemia ; Efficacy ; Imatinib ; Indirect treatment comparison ; Matching adjusted indirect comparison ; Philadelphia chromosome ; Ponatinib ; Tyrosine kinase inhibitor
Published in:	Advances in Therapy, Vol. 40 Núm. 7 (july 2023) , p. 3087-3103, ISSN 1865-8652

DOI: 10.1007/s12325-023-02497-y
PMID: 37208556

17 p, 1.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles