To the Editor: The COVID-19 pandemic, which has produced devastating effects on the health care system, has also affected the care of melanoma patients. During the first months of the pandemic, several studies from China pointed out that cancer patients infected with SARS-CoV-2 had a higher risk of complications.1 , 2 In particular, there were concerns as to whether anti-cancer drugs might increase the aggressiveness of the infection. Conversely, some recent studies from western countries have found no association between mortality and cancer treatment.3 , 4 Although an increased risk of death in patients with a cancer diagnosis is suggested, it is not fully confirmed.3, 4, 5 Most studies have included a limited number of melanoma patients (Supplemental Table I available via Mendeley at 10.17632/5b8h5hszdg.1).3, 4, 5
The Spanish Melanoma Group (GEM) started a national registry of melanoma patients infected with SARS-CoV-2 in Spain (Supplemental Fig 4). Here, we present data from the first 70 patients entered between April 1 and June 8, 2020. Thirty-nine (56%) patients had stage IV melanoma, 8 (11%) had stage III, 10 (14%) had stage II, and 14 (20%) had stage I. Thirty-six (51%) patients were undergoing active anti-cancer treatment, including 22 (31%) patients treated with anti-PD-1 antibodies and 14 (20%) with BRAF plus MEK inhibitors. Thirty-eight (54%) patients had no evidence of active tumor (no macroscopic disease). According to the Response Evaluation Criteria in Solid Tumors (RECIST) guideline, version 1.1, there were 20 (29%) patients with stable disease or tumor response and 12 (17%) with tumor progression as their best radiological response. In terms of the clinical severity of the infection, 20 (29%) patients were asymptomatic or had mild symptoms, 12 (17%) had moderate symptoms, 18 (26%) developed severe symptoms, and 20 (28%) had critical complications (Table I , Supplemental Fig 5).
Table I.
Baseline characteristics of COVID-19 infected melanoma patients according to melanoma treatment
| Characteristics | Total (N = 70) | Anti-PD-1 (N = 22) (31%) | BRAF/MEKi (N = 14) (20%) | No treatment∗ (N = 34) (49%) |
|---|---|---|---|---|
| Age, y | ||||
| Median (range) | 68 (6-95) | 68 (50-95) | 56 (6-91) | 71 (48-85) |
| Sex, n (%) | ||||
| Male | 47 (67) | 13 (59) | 8 (57) | 26 (76) |
| Melanoma stage, n (%) | ||||
| I | 14 (20) | 0 | 0 | 14 (41) |
| II | 10 (14) | 1 (4) | 0 | 9 (26) |
| III | 7 (10) | 3 (14) | 2 (12) | 2 (6) |
| IV | 39 (56) | 18 (82) | 12 (86) | 9 (26) |
| Clinical management, n (%) | ||||
| Outpatient | 21 (30) | 5 (23) | 4 (28) | 12 (35) |
| Hospitalized | 49 (70) | 17 (77) | 10 (71) | 22 (65) |
| ICU | 4 (6) | 3 (14) | 1 (7) | 0 (0) |
| COVID-19 severity, n (%) | ||||
| Asymptomatic/Mild | 20 (28) | 5 (23) | 6 (43) | 9 (26) |
| Moderate | 12 (17) | 5 (23) | 0 (0) | 7 (21) |
| Severe | 18 (26) | 6 (28) | 5 (36) | 7 (21) |
| Critical | 20 (29) | 6 (28) | 3 (21) | 11 (32) |
| COVID-19 evolution,† n (%) | 59† (100) | 18 | 12 | 29 |
| Resolved | 37 (63) | 10 (56) | 8 (66) | 19 (65) |
| Exitus by COVID-19 | 14 (21) | 4 (22) | 2 (17) | 8 (28) |
| Exitus by melanoma | 8 (13) | 4 (22) | 2 (17) | 2 (7) |
Anti-PD-1, Therapeutic anti-PD-1 antibody; BRAF/MEKi, BRAF inhibitors combined with MEK inhibitors drugs; ICU, intensive care unit; N, number of patients.
No treatment, patients who were not in active antitumoral treatment defined as time from the last antitumor treatment at least 8 weeks.
Covid-19 evolution is reported from 59 patients, indicating that COVID-19 either was resolved or those patients died.
At the time of data cutoff, the infection had resolved in 37 (63%) patients, 8 (13%) had died due to melanoma, and 14 (24%) had died due to COVID-19. There were no significant differences in the clinical severity of the infection according to melanoma therapy. Severe or critical symptoms developed in 58% of patients who were in treatment with immunotherapy, 57% of patients who were in treatment with antitumoral BRAF plus MEK inhibitors, and 53% of patients who were not receiving any active antitumoral therapy (P = .427) (Table I). The COVID-19 mortality rate was 22%, 17%, and 27% for patients with immunotherapy, targeted drug treatment, and no systemic cancer treatment, respectively (P = .787) (Table I, Supplemental Fig 1, and Supplemental Tables II and III).
Univariate analysis showed that age over 60 years and previous cardiovascular disorders increased the probability of developing severe or critical infection (odds ratio [OR] 4.25, 95% confidence interval [CI], 1.50-12.07, and OR 4.46, 95% CI, 1.13-17.58, respectively) and death (OR 11.37, 95% CI, 1.37-94.41, and OR 4.87, 95% CI, 1.25-19.06, respectively). The effect of tumor stage, melanoma treatment, and cancer control were not significant factors for the risk of developing a critical or severe COVID-19 infection or death (Fig 1 and Supplemental Figs 2 and 3). Although this analysis included a low number of cases and we cannot exclude an unintended selection bias, in our data analyses, tumor stage, active tumor, and melanoma therapies did not have a relevant impact on COVID-19 evolution.
Fig 1.
OR Plot showing effect on COVID-19 mortality. OR plot showing effect on COVID-19 mortality. Age over 60 years old and previous cardiovascular disorders increased risk of death due to COVID-19 (OR 11.37, 95% CI 1.37-94.41, P = .024 and OR 4.87, 95% CI 1.25-19.06, P = .022, respectively). Patients with 3 or more co-morbidities had higher risk of death due to COVID-19 (OR 4.00, 95% CI 1.12-14.35, P = .033). Previous diagnose of hypertension or diabetes mellitus did not increased the risk of death (OR 1.24, 95% CI 0.37-4.18, P = .734 and OR 3.20, 95% CI 0.72-14.15, P = .125, respectively). The effect of sex and smoking status were not significant factor for the risk of death due to COVID-19 (OR 2.23, 95% CI 0.54-9.13, P = .266 and OR 1.17, 95% CI 0.34-3.96, P = .805, respectively). BRAF plus MEK inhibitors combination did not increase the mortality risk by COVID-19 (OR 0.53, 95% CI 0.09-2.94, P = .463). Immunotherapy treatment did not increase the risk of death by COVID-19 (OR 0.75, 95% CI 0.19-2.97, P = .682). The effect of advanced stage was not a significant factor for the risk of death by COVID-19 (OR 0.61, 95% CI 0.18-2.03, P = .4184). The effect of a previous melanoma complete surgical resection was not a significant factor for the risk of death due to COVID-19 infection (OR 1.37, 95% CI 0.41-4.56, P = .609). ORs with 95% Wald confidence limits. CI, Confidence interval; OR, odds ratio.
Conflicts of interest
None disclosed.
Acknowledgments
The authors thank Stephanie Davis for writing assistance.
Footnotes
Funding sources: This study has been funded by Spanish Melanoma Group. It has not been sponsored by any pharmaceutical company.
IRB approval status: Reviewed and approved by the Ethics Committee of the Hospital Puerta del Hierro, Madrid (Exp. 6/2020).
Reprints not available from the authors.
References
- 1.Zhang L., Zhu F., Xie L., et al. Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China. Ann Oncol. 2020;31(7):894–901. doi: 10.1016/j.annonc.2020.03.296. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Dai M., Liu D., Liu M., et al. Patients with cancer appear more vulnerable to SARS-CoV-2: a multicenter study during the COVID-19 outbreak. Cancer Discov. 2020;10(6):783–791. doi: 10.1158/2159-8290.CD-20-0422. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Lee L.Y.W., Cazier J.B., Angelis V., et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet. 2020;395(10241):1919–1926. doi: 10.1016/S0140-6736(20)31173-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Kuderer N.M., Choueiri T.K., Shah D.P., et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet. 2020;395(10241):1907–1918. doi: 10.1016/S0140-6736(20)31187-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Mehta V., Goel S., Kabarriti R., et al. Case fatality rate of cancer patients with COVID-19 in a New York Hospital System. Cancer Discov. 2020;10(7):935–941. doi: 10.1158/2159-8290.CD-20-0516. [DOI] [PMC free article] [PubMed] [Google Scholar]