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ATRA Plus Arsenic Trioxide Improves Long-Term QoL in Patients With APL, Yet Many Don’t Receive the Combo Therapy

December 21, 2021

January 2022

Featured research from recent issues of Blood Advances

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Patients with acute promyelocytic leukemia (APL) who received all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) reported better long-term quality of life (QoL) than patients with APL who received ATRA plus standard chemotherapy, according to research findings published in Blood Advances.1

“Over the past few decades, major advances have been made in APL research, which have turned APL from a rapidly fatal condition into a highly curable disease for many patients,” said Fabio Efficace, PhD, of the Italian Group for Adult Hematologic Diseases (GIMEMA) in Rome, Italy. “Therefore, it is now critical to better understand how we can best support these patients after treatment ends.”

The cohort study included 161 patients with APL who were part of a previous randomized, controlled trial. Dr. Efficace and colleagues assessed patient-reported outcome (PRO) measures on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20), and the Short Form Health Survey 36 (SF-36).

A total of 83 patients in the study received treatment with ATRA plus ATO, while 78 received treatment with ATRA plus chemotherapy. Overall, the median duration since diagnosis was eight years, and the median age of the population was 55.2 years.

An analysis of the three health-related QoL scales showed a clinically meaningful difference between the two treatment groups, with greater benefits associated with ATRA plus ATO for improvements in role functioning (p=0.037) and lower dyspnea severity (95% CI -16.4 to -0.7). The investigators reported other clinically relevant differences that favored the ATRA plus ATO treatment group, including those for global QoL (95% CI 21.4-13.5), physical functioning (95% CI 20.2-12.0), and pain (95% CI 217.1-0.7).

Regarding the results on the SF-36, there was a clinically relevant better physical component score for patients who received ATRA plus ATO versus ATRA and chemotherapy (95% CI 1.3-7.8), but the investigators did not find a difference between the two treatment groups for the mental component score.

Comorbid conditions among patients in the study sample included hypertension (32.9%), impaired vision (29.8%), back pain (29.2%), osteoarthritis (18%), depression (15.5%), allergies (14.9%), impaired hearing (14.3%), and thyroid disorders (10.6%). Overall, approximately 78% of patients in each treatment group reported at least one comorbidity. Both treatment groups had comparable profiles in the scores of the EORTC QLQ-CIPN20 scale, and both groups had a similar prevalence of late comorbidities.

“Considering the high survival rates of APL patients with current ATO-based therapies, we can expect a growing population of APL survivors over the coming years, and we need to offer them high-quality supportive care programs,” Dr. Efficace said. “Therefore, inclusion of PROs in future APL studies will be critical to keep accumulating evidence-based data on how to best address most relevant problems faced by these patients and improve healthcare delivery.”

Despite this QoL benefit associated with ATRA plus ATO, many patients with APL do not receive this or other guideline-concordant therapy and, consequently, experience increased adverse outcomes, according to a recent study published by Jan Philipp Bewersdorf, MD, of Yale School of Medicine, and colleagues in Blood Advances.2

“The wide use of ATRA and ATO has revolutionized the management of APL with the vast majority of APL patients achieving cure from this previously lethal and aggressive form of acute leukemia,” said corresponding study author Amer Zeidan, MBBS, also from Yale. “Nonetheless, most of the data regarding improved outcomes of patients come from clinical trials that enrolled highly selected patients who were generally managed by experienced leukemia specialists.”

Dr. Zeidan and colleagues conducted an analysis of U.S.-based practice patterns, with a focus on 1,464 patients with newly diagnosed APL who were included in the Vizient Clinical Data Base. The researchers used baseline white blood cell (WBC) counts to assign each patient’s risk status and evaluate treatment in concordance with the National Comprehensive Cancer Network (NCCN) guidelines.

Individuals with a WBC count of >10×109/L were designated as high-risk patients, while those with WBC counts ≤10×109/L were classified as low risk. Treatments considered concordant with the guidelines in low-risk patients were those that included ATRA plus either ATO, an anthracycline, or gemtuzumab ozogamicin. In high-risk patients, guideline-concordant treatment included ATRA plus arsenic plus anthracycline or gemtuzumab ozogamicin, ATRA plus anthracycline, and ATRA plus gemtuzumab ozogamicin.

Approximately 14% of the patient population (n=205) experienced an adverse outcome, including either inpatient mortality (12.3%) or discharge to hospice (1.7%). The rate of adverse outcomes was highest in high-risk patients (26.8%) compared with low- and unknown-risk patients (7.4% vs. 14.0%, respectively).

Slightly more than one out five patients did not receive treatment regimens concordant with the NCCN guidelines. The odds of adverse outcomes increased with failure to receive these guideline-recommended approaches (odds ratio [OR] = 2.31; 95% CI 1.43-3.75; p=0.001). The odds of adverse outcomes in these patients increased with the lack of guideline-concordant therapy (OR=2.31; 95% CI 1.43-3.75; p=0.001), high-risk disease (OR=2.48; 95% CI 1.53-4.00; p<0.001), and increasing age (≥60 years; OR=11.13; 95% CI 4.55-27.22; p<0.001).

Additionally, the investigators reported an association between higher hospital volume of patients with acute myeloid leukemia (AML) and lower odds of adverse outcome (≤50 vs. >200 patients with AML per year; OR=0.44, 95% CI 0.20-0.99; p=0.046).

Given the retrospective nature of the study, the researchers noted that they were unable to confirm the APL diagnoses by molecular testing results and instead relied on the International Classification of Diseases, 10th Revision (ICD-10), diagnosis codes. The researchers were also unable to assess physician intent regarding treatment choice, nor did they evaluate whether comorbid conditions potentially affected treatment decisions.

Despite these limitations, the investigators wrote that the findings “highlight the need for ongoing practice improvement in the real-world setting and suggest lower rates of guideline-concordant therapy as a contributing factor to worse outcomes compared with clinical trials.”

Study authors report no relevant conflicts of interest.

References

  1. Efficace F, Platzbecker U, Breccia M, et al. Long-term quality of life of patients with acute promyelocytic leukemia treated with arsenic trioxide vs chemotherapyBlood Adv. 2021;5(21):4370-4379.
  2. Bewersdorf JP, Prozora S, Podoltsev NA, et al. Practice patterns and real-life outcomes for patients with acute promyelocytic leukemia in the United States [published online ahead of print, 2021 Nov 1]. Blood Adv. doi: 10.1182/bloodadvances.2021005642.

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