The <scp>PINNACLE</scp> study: A multicentre phase <scp>II</scp> trial of nilotinib in combination with pegylated interferon‐α2b in newly diagnosed chronic phase chronic myeloid leukaemia

We evaluated the tolerability and efficacy of pegylated interferon alfa-2B (peg-IFNα; PegIntron, MSD) combined with nilotinib in the Australasian Leukaemia and Lymphoma Group CML11 (Pinnacle) study. This phase II study started patients on nilotinib 300 mg twice daily. Subcutaneous peg-IFNα was added at 30-50 50 μg/week from 3 months until 24 months as tolerated. Sixty patients were enrolled with a median age of 48.5 years (range 19-72); 45% were female. With a median follow-up of 60 months, 40 patients (67%) remain on study. The proportion of patients who received ≥50% and ≥85% of their assigned peg-IFNα doses were 58% and 35% respectively. Common reasons for peg-IFNα discontinuation were mood disturbance (5), thyroid disease (4) and myalgia (4). The cumulative incidence of Major Molecular Response (MMR, BCR::ABL1≤0.1%) was 87% by 12 months; Molecular Response 4.5 (MR4.5, BCR::ABL1≤0.0032%) incidence at 24 and 60 months was 55% and 82% respectively. Thirty-seven patients (62%) had MR4.5 for >24 months, 14 of whom attempted treatment-free remission (TFR); 13 remained in TFR at a median follow-up of 32 months. CML11 demonstrated that peg-IFNα with nilotinib leads to high rates of molecular response, with tolerability similar to prior studies. Trial registration ANZCTRN12612000851864.

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Journal
British Journal of Haematology
Published
2025-12-22
DOI
https://doi.org/10.1111/bjh.70276
Primary Topic
Chronic Myeloid Leukemia Treatments
Type
article
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article

The PINNACLE study: A multicentre phase II trial of nilotinib in combination with pegylated interferon‐α2b in newly diagnosed chronic phase chronic myeloid leukaemia

Nicholas Viiala, Susan Branford, Rosemary Anne Harrup, Deepmala Mazumdar et al.
British Journal of Haematology
Chronic Myeloid Leukemia Treatments
article

The PINNACLE study: A multicentre phase II trial of nilotinib in combination with pegylated interferon‐α2b in newly diagnosed chronic phase chronic myeloid leukaemia

Nicholas Viiala, Susan Branford, Rosemary Anne Harrup, Deepmala Mazumdar, Christopher Arthur, Deborah L. White, Naranie Shanmuganathan, Anthony K. Mills, David Kipp, Ilona Cunningham, Anthony P. Schwarer, Robert Weinkove, Sher Gul Gazdar, John Reynolds, David T. Yeung, Jake Shortt, Timothy Hughes, Andrew P. Grigg, Agnes S. M. Yong, the Australasian Leukaemia and Lymphoma Group, David M. Ross, Kathryn Jackson, Philip Rowlings
article en

Abstract

We evaluated the tolerability and efficacy of pegylated interferon alfa-2B (peg-IFNα; PegIntron, MSD) combined with nilotinib in the Australasian Leukaemia and Lymphoma Group CML11 (Pinnacle) study. This phase II study started patients on nilotinib 300 mg twice daily. Subcutaneous peg-IFNα was added at 30-50 50 μg/week from 3 months until 24 months as tolerated. Sixty patients were enrolled with a median age of 48.5 years (range 19-72); 45% were female. With a median follow-up of 60 months, 40 patients (67%) remain on study. The proportion of patients who received ≥50% and ≥85% of their assigned peg-IFNα doses were 58% and 35% respectively. Common reasons for peg-IFNα discontinuation were mood disturbance (5), thyroid disease (4) and myalgia (4). The cumulative incidence of Major Molecular Response (MMR, BCR::ABL1≤0.1%) was 87% by 12 months; Molecular Response 4.5 (MR4.5, BCR::ABL1≤0.0032%) incidence at 24 and 60 months was 55% and 82% respectively. Thirty-seven patients (62%) had MR4.5 for >24 months, 14 of whom attempted treatment-free remission (TFR); 13 remained in TFR at a median follow-up of 32 months. CML11 demonstrated that peg-IFNα with nilotinib leads to high rates of molecular response, with tolerability similar to prior studies. Trial registration ANZCTRN12612000851864.

British Journal of HaematologyVol. 208(2)
Concord Hospital (US), Royal Adelaide Hospital (AU), Barwon Health (AU), Box Hill Hospital (AU), Malaghan Institute of Medical Research (NZ), Geelong Hospital (AU), Royal Perth Hospital (AU), Royal North Shore Hospital (AU), Concord Repatriation General Hospital (AU), Liverpool Hospital (AU), Monash Medical Centre (AU), Princess Alexandra Hospital (AU), Flinders Medical Centre (AU), Royal Hobart Hospital (AU), Sunshine Coast University Hospital (AU), South Australian Health and Medical Research Institute (AU), Centre for Cancer Biology (AU), Calvary Mater Newcastle Hospital (AU), Australasian Leukaemia and Lymphoma Group (AU), Austin Health (AU), Monash University (AU)
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Openalex Percentile: Top 25%
Chronic Myeloid Leukemia Treatments
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