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Clinical Trial
. 2021 Mar;10(5):1726-1737.
doi: 10.1002/cam4.3778. Epub 2021 Feb 16.

Molecular response and quality of life in chronic myeloid leukemia patients treated with intermittent TKIs: First interim analysis of OPTkIMA study

Michele Malagola  1 , Alessandra Iurlo  2 , Elisabetta Abruzzese  3 , Massimiliano Bonifacio  4 , Fabio Stagno  5 , Gianni Binotto  6 , Mariella D'Adda  7 , Monia Lunghi  8 , Monica Crugnola  9 , Maria Luisa Ferrari  10 , Francesca Lunghi  11 , Fausto Castagnetti  12 , Gianantonio Rosti  13 , Roberto M Lemoli  14 , Rosaria Sancetta  15 , Maria Rosaria Coppi  16 , Maria Teresa Corsetti  17 , Giovanna Rege Cambrin  18 , Atelda Romano  19 , Mario Tiribelli  20 , Antonella Russo Rossi  21 , Sabina Russo  22 , Lara Aprile  23 , Monica Bocchia  24 , Lisa Gandolfi  1 , Mirko Farina  1 , Simona Bernardi  1   25 , Nicola Polverelli  1 , Aldo M Roccaro  26 , Antonio De Vivo  12 , Michele Baccarani  27 , Domenico Russo  1
Affiliations
Clinical Trial

Molecular response and quality of life in chronic myeloid leukemia patients treated with intermittent TKIs: First interim analysis of OPTkIMA study

Michele Malagola et al. Cancer Med. 2021 Mar.

Erratum in

  • Corrigendum.
    [No authors listed] [No authors listed] Cancer Med. 2021 May;10(10):3486. doi: 10.1002/cam4.3922. Epub 2021 May 2. Cancer Med. 2021. PMID: 33934555 Free PMC article. No abstract available.

Abstract

Background: Intermittent treatment with TKIs is an option for the great majority (70%-80%) of CML patients who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation. For these patients, the only alternative is to assume TKI continuously, lifelong.

Methods: The Italian phase III multicentric randomized OPTkIMA study started in 2015, with the aim to evaluate if a progressive de-escalation of TKIs (imatinib, nilotinib, and dasatinib) is able to maintain the molecular response (MR3.0 ) and to improve Health Related Quality of Life (HRQoL).

Results: Up to December 2018, 166/185 (90%) elderly CML patients in stable MR3.0 /MR4.0 completed the first year of any TKI intermittent schedule 1 month ON and 1 month OFF. The first year probability of maintaining the MR3.0 was 81% and 23.5% of the patients who lost the molecular response regained the MR3.0 after resuming TKI continuously. Patients' HRQoL at baseline was better than that of matched peers from healthy population. Women was the only factor independently associated with worse baseline HRQoL (p > 0.0001). Overall, global HRQoL worsened at 6 (p < 0.001) but returned to the baseline value at 12 months and it was statistically significantly worse in women (p = 0.001).

Conclusions: De-escalation of any TKI by 1 month ON/OFF schedule maintains the MR3.0 /MR4.0 in 81% of the patients during the first 12-24 months. No patients progressed to accelerated/blastic phase, all the patients (23.5%) losing MR3.0 regained the MR3.0 and none suffered from TKI withdrawn syndrome. The study firstly report on HRQoL in elderly CML patients moving from a continuous daily therapy to a de-escalated intermittent treatment.

Keywords: chronic myeloid leukaemia; intermittent; quality of life; tyrosine kinase inhibitor.

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Conflict of interest statement

AI—speaker honoraria from Novartis, Pfizer, and Incyte; EA—consultancy and advisory for Novartis, Bristol Myers Squibb, Incyte, and Pfizer; GR—speaker honoraria from Novartis, Pfizer, and Incyte; MB—consultant and receiving honoraria from Novartis, Incyte, and Takeda; DR—speaker honoraria: MSD, Novartis, Gilead; advisory committees: MSD, Janssen, Gilead. All the other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Probability of maintaining MR3.0 at 1st year of OPTkIMA
FIGURE 2
FIGURE 2
Baseline symptom profile of OPTkIMA patients versus sex and age matched peers from general population. Legend: * = clinically meaningful difference. The figure represents the age‐sex adjusted mean level of symptom burden per group
FIGURE 3
FIGURE 3
Prevalence of clinically important problems and symptoms by gender. (A) Functional scales, (B) Symptom scales. Legend: Clinically important problems and symptoms (Giesinger et al. J Clin Epidemiol. 2019 Oct 19;118:1–8)
FIGURE 4
FIGURE 4
Trajectories of change in quality of life outcomes for selected EORTC QLQ‐C30 scales. Legend: For the global QoL scale higher scores indicate better QoL outcomes, whereas lower scores indicate worse QoL outcomes. For diarrhoea, fatigue, and nausea/vomiting higher scores indicate higher symptom severity, whereas lower scores indicate lower symptom severity. P‐values refer to change from baseline
FIGURE 5
FIGURE 5
Trajectories of gender differences in Global Quality of Life up to 12 months
See this image and copyright information in PMC

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