ABSTRACT
Introduction In the first weeks of the Covid-19 pandemic when healthcare systems in many areas were overstretched, we documented that hospital mortality in multiple myeloma (MM) patients infected by Sars-Cov-2 was 50% higher than in age matched Covid-19 patients without cancer. In the following months, the pressure on healthcare systems in Spain continued although it did not reach the extreme levels of the first weeks of the pandemic. In this study, we proposed to determine if the severity of Covid-19 outcomes in MM patients has changed over the first year of the pandemic. Patients and methods The Spanish MM Collaborative Group (Pethema-GEM) conducted a survey at national level on plasma cell disorder patients infected by SARS-Cov-2 between March 2020 and February 2021. Sixty-six (69%) out of 96 contacted healthcare centers, from all 17 regions in Spain, reported 502 patients. Data on Covid-19 acute and post-acute phase outcomes (hospitalization, oxygen requirements, severity of symptoms and mortality) were reported first in May 2020 (Martinez-Lopez et al, BCJ 2021) and updated in February 2021. In this study, we compared outcome occurrence between two study periods: P1, a period of extreme stress for the healthcare system in Spain, from March to mid-June 2020;and a second period, P2, up to mid-February 2021 with a sustained but lower burden on the national health care system. Results Among the 451 patients with plasma cell disorders and a Sars-Cov-2 infection documented with an rRT-PCR positive test, 377 (84%) were MM patients, 15 SMM (3%), 40 MGUS (9%) and 19 amyloidosis (4%). The number of MM weekly reported cases was 57% (95%CI, 48-65) lower in P2 (188 cases in 35 weeks) compared to P1 (189 cases in 15 weeks), p<0.001. The mean (SD) age and the proportion of men did not differ between P1 and P2, respectively 69.8 (10.9) vs 68.6 (11.0) years, p=0.6, and 53.3% vs 59.6%, p=0.2. MM patients with active or progressive disease at time of Covid-19 diagnosis were 24% in P1 and 34% in P2, p=0.05;patients on active treatment were more frequent in P1, 89%, than in P2, 79%, p=0.01. MM treatment was withheld in 78% and 82% of patients, p=0.4. Covid-19 treatment changed over time: MM inpatients received more remdesivir and corticoids in the second period (3% vs 31% p<0.001, and 49% vs 73%, p<0.001, respectively). In P1, 90% of the reported MM patients were hospitalized compared to 71% in P2, p<0.001. Thirty-one and 41% of patients did not require oxygen support during P1 and P2, respectively;non-invasive ventilation in 19% and 14%, and mechanical ventilation in 7% and 8%, p=0.12. Overall, acute clinical Covid-19 severity was reduced from P1 to P2: 75% to 51%, p<0.001: moderate/severe pneumonia was reduced from 68% to 36%, p<0.001 but severe distress syndrome increased from 7% to 15%, p=0.03. However, mortality in all reported patients was 30.7% in P1 vs 26.1% in P2, p=0.3;and no differences in mortality were observed in hospitalized patients, 32.2% in P1 and 35.3% in P2, p=0.6. We performed a multivariable adjustment with the predictors identified in our previous study (BCJ 2021) and confirmed that inpatient mortality was similar in both study periods, odds ratio (OR) 0.99 (95%CI 0.59-1.66). Independently of the study period, an increased mortality was observed in men (OR 1.81, 1.08-3.05), patients over 65 (OR 2.40, 1.33-4.36), and patients with active or progressive disease (OR 2.12, 1.24-3.62). The severity of Covid-19 clinical outcomes -besides mortality, was associated with increased age but not with active or progressive disease. Conclusions Although COVID-19 clinical severity has decreased over the first year of the pandemic in multiple myeloma patients, mortality remains high with no change between the initial weeks of the pandemic and the following months. Prevention and vaccination strategies should be strengthened in this vulnerable population, particularly in patients with active or progressive disease at time of Covid-19 diagnosis. Disclosures: Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfi er: Consultancy;Roche, Novartis, Incyte, Astellas, BMS: Research Funding. Mateos: Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees;Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: 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;Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Bluebird bio: Honoraria;GSK: Honoraria;Oncopeptides: Honoraria. López-Muñoz: Amgen: Consultancy. Sureda: GSK: Consultancy, Honoraria, Speakers Bureau;Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche: Other: Support for attending meetings and/or travel;Mundipharma: Consultancy;Bluebird: Membership on an entity's Board of Directors or advisory committees;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;MSD: Consultancy, Honoraria, Speakers Bureau;BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau;Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Lahuerta: Celgene, Takeda, Amgen, Janssen and Sanofi: Consultancy;Celgene: Other: Travel accomodations and expenses. San-Miguel: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Merck Sharpe & Dohme, Novartis, Regeneron, Roche, Sanofi, SecuraBio, Takeda: Consultancy, Other: Advisory board.
ABSTRACT
Introduction: COVID-19 is thought to be more frequent and severe in patients with cancer. Lymphoma patients may be especially vulnerable, due to the immunodeficiency and immune dysregulation caused by the lymphoma itself and the antitumor treatments. This study describes the characteristics and outcomes of lymphoma patients after developing COVID-19. Methods: This is a retrospective multicentre study carried out in the hospitals of the GELTAMO group, which included patients with a histological diagnosis of lymphoma and confirmed SARS-COV-2 infection before June 30th, 2020. The primary outcome was overall survival (OS) 60 days after a COVID-19 diagnosis. Results: A total of 218 patients (median sage 69.5 [21-94] years, 54% male) were included;100 patients had an indolent B-cell non-Hodgkin's lymphoma (NHL), 67 aggressive B-cell NHL, 19 mantlecell lymphoma, 15 peripheral T-cell lymphoma, and 17 Hodgkin's lymphoma. Patients had received a median of 1 line (0-7) of therapy, and 44.9% were on active treatment at the time of COVID-19 diagnosis. Only 6.4%, 1.8% and 0.9% of patients had received previously autologous stem-cell transplantation, allogeneic SCT and CAR-T cell therapy, respectively. 89% of patients were hospitalized, 71% required oxygen, and 15% mechanical ventilation. With a median follow-up of 91.5 days (13-203), 65 patients have died (60 from COVID-19, 4 from lymphoma, 1 due to other causes), with an estimated 60-day OS of 68.6% (95% CI 62.1-75.1) (figure 1A). In univariate analysis, baseline characteristics associated with decreased OS were age ≥70 years, hypertension, diabetes, other cancer, active disease and hypogammaglobulinemia, but only age ≥70 years maintained independent influence in the multivariate analysis (HR 3.29, 95% CI 1.86-5.83, p < 0.001). Active treatment did not significantly impact OS (figure 1B). Univariate analysis revealed different prognostic factors, apart from age, for patients with DLBCL (N = 60) and FL (N = 69). While the presence of active disease had a prognostic impact on DLBCL (60-day OS 56% vs 79%, p = 0.038) but not on FL (60-day OS 65% vs 78%, p = 0.181) patients, the opposite occurred in the case of active treatment, which seemed to have a negative influence only in patients with FL, as shown in figures 1C and 1D. Conclusions: Our results confirm a high mortality in patients with lymphoma and COVID-19, especially in those ≥70 years old. In patients with DLBCL, disease control seems essential to reduce the risk of mortality in the event of contracting the infection. By contrast, in patients with FL, delaying the start of treatment until it is not strictly necessary should be considered, and these patients should be prioritized to be vaccinated before starting antitumor treatment. This study provides initial data to develop recommendations for the management of lymphoma patients during the COVID-19 pandemic.