COVID-19 in Patients (pts) with Chronic Myeloid Leukemia (CML): Results from the International CML Foundation (iCMLf) CML and COVID-19 (CANDID) Study

Abstract

Background Comorbid conditions, including solid and hematologic malignancies, may impact risk of contracting SARS CoV-2 or having severe COVID-19. Data specific to individual cancer types is essential to differentiate impact of patient, disease, and therapy specific factors on risk and outcomes, as the pandemic remains uncontrolled. Goal The primary goal of the CANDID study was to rapidly collect and analyze information on COVID-19 cases among CML pts to define prognosis, risk factors and outcome. Defining risk and predisposing features in CML patients could guide interventions, therapy modifications, and clinical management for patients and physicians. Methods From March 12, 2020, the iCMLf sent an anonymized case collection form to its global network of physicians treating CML pts and partner organizations. Forms were reviewed and cases tracked by an iCMLf data manager. Updates were provided weekly. Only confirmed cases or those with high level of suspicion were collected. Denominators regarding affected cohort (% tested, % affected in CML population) were not available in most instances. Results As of July 1, 2020, 110 cases of COVID-19 were reported to iCMLf from 20 countries: 61% from Europe, 15% from Asia, 12% from South America, 10% from North America, 2% from Africa and 1% from Oceania. COVID-19 was diagnosed by PCR and/or serology in 93 pts (85%) and clinically suspected in 17 pts (15%). Forty-six physicians reported 91 of the CML pts with COVID-19 out of a total of 12,236 CML pts that they were following (0.7%). Median age at the time of COVID-19 diagnosis was 54 years (range: 18-89) and 55% of pts were males. Median time from CML diagnosis to COVID-19 was 7 years (range: 0-25). CML treatment at the time of COVID-19 diagnosis consisted of hydroxyurea in 1 pt (1%) and TKI in 77 (70%). Five (5%) pts were taking bosutinib, 12 (11%) dasatinib, 39 (36%) imatinib, 17 (16%), nilotinib, 2 (2%) ponatinib, 1 (1%) HQP1315 and 1 pt (1%) was treated with an unknown TKI. Eighteen (16%) pts were untreated at the time of COVID-19 diagnosis, 8 due to elective treatment discontinuation (TFR) and 10 for other reasons (toxicity (5), stem cell transplantation (1), unknown (1) and newly diagnosed CML (3)). CML treatment information was lacking at the time of cut-off in 14 cases (13%). Thirty-three (30%) cases were reported as having interrupted TKI therapy during COVID-19. From 110 reports COVID-19 was asymptomatic in 8 cases (7%). In the 102 symptomatic pts (93%), COVID-19 was considered as mild (no hospitalization) in 49 cases (45%), moderate (hospitalization) in 19 cases (17%), severe (intensive care) in 19 cases (17%) and of unknown severity in 15 cases (14%). At the data cut-off date, COVID-19 was still active in 14 pts (13%) and outcome was unknown in 9 pts (8%). Among the 87 others, outcome was favorable in 75 pts (86%) and fatal in 12 (14%). We analyzed overall survival in the 87 patients with known outcome according to sex, age, CML duration, type of CML treatment, line of TKI therapy, history of smoking, comorbidities, TKI interruption due to COVID-19, administration of any treatment against COVID-19 (antimicrobial agents, steroids, oxygen or anti-IL-6 antibodies) and economic status of country. Univariate analysis identified older age (75 vs < 75 years; mortality rate: 60% vs 7%, p<0.001), severity of COVID-19 (severe v non-severe; mortality 63% vs 0%, p<0.001) and imatinib treatment (mortality: imatinib 25% vs 2nd gen TKI 3% vs no TKI 0%, p=0.003) as predictors for COVID-19 mortality (Figure 1). Notably, 25% of imatinib treated patients were over 75years old, compared to none of the patients treated with second generation TKI. Conclusion The CANDID study represents the largest global cohort study to date characterizing COVID-19 in CML. Currently, the mortality rate from COVID-19 in evaluable CML patients is 13.7%. Factors associated with a higher mortality rate are age and imatinib therapy. Imatinib may represent a confounder as opposed to a true adverse prognostic predictor given the strong link between imatinib treatment and advanced age. Further case reports and longer follow up are needed to better ascertain independent risk factors, the impact of COVID-19, and the possible role that TKI type may play in this population. Acknowledgment The authors thank Arlene Harriss-Buchan from the iCMLf for case collection and reporting and the 61 physicians from 20 countries who contributed case reports. Disclosures Rea: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mauro:Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Pfizer: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Sun Pharma/SPARC: Research Funding; Novartis: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding. Cortes:BiolineRx: Consultancy, Research Funding; Arog: Research Funding; Amphivena Therapeutics: Research Funding; Astellas: Research Funding; Telios: Research Funding; BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sun Pharma: Research Funding; Takeda: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Immunogen: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Merus: Research Funding. Pagnano:Novartis: Other: Advisory Board; Astellas: Other: Advisory Board and lecture; Pintpharma: Other: Lecture; EMS: Other: Lecture. Hughes:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Foundation:Novartis: Other: Grants and sponsorship; BMS: Other: Grants and sponsorship; Pfizer: Other: Grants; Incyte: Other: Grants; Takeda: Other: Grants and sponsorship; Cepheid: Other: Grants and sponsorship.

Mental Health in Persons With Chronic Myeloid Leukemia During the SARS-CoV-2 Pandemic: The Need for Increased Access to Health Care Services

“…During the pandemic, although the likelihood of developing a COVID-19 infection in persons with CML is very low ( 28 – 31 ), negative impact on different aspects of CML management including TKI therapy response monitoring, TKI therapy, and enrollment in and compliance with clinical trials is also reported ( 29 ). These highlighted the importance of adequate access to health care services such as patient education of having appropriate personal self-protection equipment, establishing a safe area in the hospital or clinic, and telemedicine and mailed medicine to avoid monitoring and therapy interruptions 1 , 2 , 3 ( 44 – 50 ).…”

“…The IES-R (range, 0-88) was used to assess subjective distress (excessive panic and anxiety) caused by traumatic events including traumarelated distressing memories and persistent negative emotions resulting from the pandemic, which is composed of three subscales to measure the avoidance, intrusion, and hyper-arousal. The total IES-R score was categorized as follows: subclinical (0-8), mild (9-25), moderate (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43), and severe (44-88) (37). Respondents who had the scores greater than the cutoff threshold of 10 in PHQ-9, 10 in GAD-7, and 26 in IES-R indicate moderate to severe depression, anxiety, and distress, respectively, and IES-R score ≥ 26 is associated with post-traumatic stress disorder (PTSD) symptoms (35,38,39).…”

“…Data from before the pandemic indicate that persons with CML experience more severe depression and/or anxiety to daily life challenges compared with controls ( 23 – 27 ). Several studies reported prevalence and/or severity of SARS-CoV-2-infection and of coronavirus infectious disease 2019 (COVID-19) in persons with CML ( 28 – 31 ) compared with controls. There are no data on the mental health of persons with CML during the SARS-CoV-2 pandemic.…”

Evidence of robust memory T‐cell responses in patients with chronic myeloproliferative neoplasms following infection with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2)

“…However, the extent to which immunocompromised patients are able to mount a ‘normal’ immune response to SARS‐CoV‐2 remains unknown. Collaborative cohort analyses reporting clinical sequelae following SARS‐CoV‐2 infection in patients with either a classical ‘Philadelphia Chromosome’ negative myeloproliferative neoplasm (MPN) or chronic myeloid leukaemia (CML) have recently been published 2,3 . Outcomes were varied but, to date, older patients, those with myelofibrosis (MF) and those who had sudden discontinuation of the Janus kinase (JAK) inhibitor (JAKi) ruxolitinib had worse outcomes.…”

“…Higher risks were also identified for ruxolitinib discontinuation following infection. The CANDID CML study reported on 110 patients with SARS‐CoV‐2 infection, 70% of whom were on TKIs 3 . Univariate analysis revealed age >75 years, severe infection and use of imatinib (likely surrogate marker of older age) as adverse risk factors.…”