ABSTRACT
Background: Research on the impact of COVID-19 on different patient populations has been of great value for the optimization of patient care since the start of the SARS-CoV-2 pandemic. Earlier, we reported the interim analysis of the immediate outcomes in patients (pts) with hematologic (hem) disease and COVID-19. Long-term results of the CHRONOS19 registry are now available. Methods: CHRONOS19 is an observational prospective cohort study among adult pts ((≥18 years) with hem diseases (malignant or non-malignant) and laboratory-confirmed or suspected (based on clinical symptoms and/or CT) COVID-19 in Russia. Data from 15 centers all over the country were collected on a web-based platform in a de-identified manner at 30, 90, and 180 days after COVID-19 was diagnosed. The primary endpoint was 30-day all-cause mortality. Secondary outcomes included COVID-19 complications, rate of ICU admission and mechanical ventilation, outcomes of hem disease in SARS-CoV-2 infected pts, overall survival, and risk factors for disease severity and mortality. Results: As of July 30, 2021, 666 pts were enrolled (females / males [n (%)]: 317 (48%) / 349 (52%);median [range] age: 56 [18-90] years. Disease types (malignant/non-malignant [n (%)]): 618 (93%) / 48 (7%), including AML 115 (17%), MM 113 (17%), NHL 106 (16%), CML / CMPD 92 (14%), ALL 52 (8%), CLL 50 (8%), MDS 25 (4%), HCL 23 (3%), HL 21 (3%), AA 16 (2%), APL 11 (2%), others 42 (6%);among them induction phase / remission / relapse or refractory / NA in 237 (35%) / 231 (35%) / 152 (23%) / 46 (7%) pts. Concomitant conditions were reported in 385 (58%) pts: cardiovascular 254 (66%), diabetes 76 (20%), obesity 57 (15%), pulmonary 41 (11%), chronic renal 44 (11%) or hepatic 33 (9%) disease, other 90 (23%). At a median follow-up of 7,5(1-19) months, 618 pts were evaluable for the primary outcome. Thirty-day all-cause mortality was 16% (100 pts died). Death due to COVID-19 complications occurred in 82 pts, 14 pts died due to progression of hem disease. Overall, 217 (33%) pts had severe disease, COVID-19 complications were detected in 458 (70%) pts, the most common were pneumonia in 425 (93%) pts, respiratory failure in 252 (55%) pts, multiple organ failure in 56 (12%) pts, cytokine storm in 52 (11%) pts, ARDS in 47 (10%) pts, and sepsis in 44 (10%) pts. The rate of ICU admission was 23% (145 pts) with high mortality in this group of pts (77%), 111 (17%) pts required mechanical ventilation, among them only 5 (4.5%) pts survived. Treatment of hem disease was changed, interrupted, or discontinued in 395 (60%) pts with a median delay of 4 weeks. At 30 days, the rate of relapse / progression of hem disease was 5% / 8% (24 / 40 of 517 evaluable pts). At the longer follow-up (90 and 180 days), relapse / progression occurred in another 9 / 23 pts. At the data cutoff, the median overall survival was not reached. Antibody detection was performed in 253 pts: 211 (84%) pts had IgG to SARS-CoV-2. In a univariate analysis, older age (> 60 years), myelotoxic agranulocytosis, transfusion dependence, diabetes among comorbidities, ARDS and other complications, except CRS, ICU and mechanical ventilation (Fig. 1) were associated with higher risks of mortality (p<0.05). The final results of the CHRONOS19 study will be presented. Conclusions: Patients with hem disease and COVID-19 have higher mortality than a general population with SARS-CoV-2 infection, predominantly due to COVID-19 complications. The longer-term follow-up did not reveal any concerns in terms of hem disease outcomes. [Formula presented] Disclosures: Vorobyev: Janssen, Roche, Sanofi, Takeda, Biocad, Abbvie: Other: Advisory Boards, Speakers Bureau;Astellas, Novartis, AstraZeneca: Speakers Bureau. Chelysheva: Pharmstandart: Speakers Bureau;Pfizer: Speakers Bureau;Bristol Myers Squibb: Speakers Bureau;Novartis Pharma: Speakers Bureau.
ABSTRACT
Background: Since SARS-CoV-2 infection heavily affects vulnerable populations including those with immune suppression, it is of special value to study clinical course, treatment outcomes, and immunity in patients (pts) with hematological (hem) malignancies. Methods: CHRONOS19 is an ongoing observational study in adult pts (≥18 years) with hem diseases (malignant or non-malignant) and COVID-19 in Russia. This web-based registry collected de-identified data from 15 centers all over the country at 30, 90, and 180 days after lab-confirmed or suspected (based on CT and/or clinical symptoms) COVID-19 diagnosis. The primary endpoint was 30-day all-cause mortality. Results: As of data cut-off on April 14, 2021, 626 pts were enrolled in the study;562 were eligible for primary endpoint assessment, n (%): M/F 271 (48%) / 291 (52%), median age 56 [18-90] years, malignant disease in 516 (92%) pts, among them induction phase / relapse or refractory / remission / NA in 180 (35%) / 120 (23%) / 187 (36%) / 29 (6%) pts. Thirty-day all-cause mortality in pts with hem malignancies was 19%;83% of deaths were due to COVID-19 complications. No increase of hem disease relapse rate after COVID-19 was observed at Day 90 or Day 180, although 180-day data was still not mature at the time of analysis. IgG to SARS-CoV-2 was detected in 84% of pts with hem malignancies (167/199). The highest rate of detected antibody immunity was found in pts with chronic myeloproliferative neoplasms (100%;13/13), HL (100%;12/12), and multiple myeloma (97%;34/35), the lowest – in pts with CLL (62%;8/13) and NHL (60%;6/10 and 56%;10/18 for low-grade and high-grade lymphoma, respectively). igG detection rate in CD20+ lymphoma (60%) was significantly lower than in HL or T-cell lymphoma (p=0.004). Pts with ECOG 0-2 throughout the disease had a high rate of antibody immunity (90%;104/116) vs. those with ECOG 3-4 at the time of COVID-19 diagnosis (77.5%;31/40) or with worsening of ECOG to 3-4 during the disease (78%;36/46). Five cases of SARS-CoV-2 re-infection were described. Conclusions: Pts with hem malignancies and COVID-19 have higher mortality than the general population. Low post-disease antibody immunity to SARS-CoV-2 and cases of re-infection may justify vaccination of these pts and warrant further research. Clinical trial identification: NCT04422470. Legal entity responsible for the study: National Research Center for Hematology. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
Background: Patients (pts) with acute leukemia (AL) are at high risk of COVID-19 severe and lethal course. Intensive chemotherapy and immunosuppression in these patients are the possible causes of high mortality. Emerging data on risk factors and outcomes in this vulnerable patient population is aimed to support strategies of their medical care. Aims: To evaluate treatment outcomes and risk factors in pts with AL and COVID-19 in a real-world setting. Methods: CHRONOS19 [NCT04422470] is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hematologic disease (both malignant and non-malignant) and lab-confirmed or suspected (based on clinical and/or CT findings) COVID-19. We performed a subgroup analysis of pts with AL and COVID-19. Primary objective was to evaluate treatment outcomes and identify risk factors associated with higher mortality in this group of pts. Primary endpoint was 30-day all-cause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web-based platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 132 of them with AL were eligible for primary endpoint assessment n(%): AML - 86(65%), ALL - 37(28%), APL - 9(7%);M/F 55(42%)/77(58%), median age 45 [18-79] years, induction phase/R/R/ treatment in remission 49(37%)/27(21%)/ 54(42%), agranulocytosis in 55(42%) pts, 68(53%) pts were transfusion dependent, comorbidities - in 58(45%) pts. Complications developed in 98(74%) pts: pneumonia (71%), sepsis (9%), CRS (8%), ARDS (6%). One-third of pts had severe COVID-19, 30% were admitted to ICU, 26% required mechanical ventilation. We performed comparative analysis of characteristics between a group of pts with AL and other hematologic diseases (lymphomas, chronic leukemia, multiple myeloma, and other malignant and non-malignant diseases): pts with AL had significantly more frequent agranulocytosis (42% vs 20%, p<0,001), transfusion dependence (53% vs 33%, p<0,001), and a higher rate of admission to ICU (30% vs 20%, p=0,036). All-cause mortality at 30 days was 24% in pts with AL vs. 15% in pts with other hematologic diseases (p=0,03);70% of deaths were due to COVID- 19 complications in pts with AL. At 90 days, one additional death due to COVID-19 occurred. At 180 days, 5 more deaths due to leukemia progression were registered. Risk factors that were significantly associated with overall survival (OS) are listed in Table 1. In multivariate analysis, ICU + mechanical ventilation, HR, 70.258 (19.5-270.0) and age >60 years HR, 3.340 (1.08-10.9) were the most significant risk factors of death. Overall, AL were associated with a higher risk of death, HR, 2.40 (1.28-4.51), compared to less aggressive diseases (CML, CLL, MM, lymphomas, non-malignant), HR, 0.54 (0.37-0.80). COVID-19 affected treatment of AL in 65% of pts, 58% experienced treatment delay for a median of 4 [1-10] weeks. In 11 of 103 (10,7%) pts with AL early relapse/refractory disease was detected, but the association of relapses with affected treatment is unknown. COVID-19 re-infection was described in 2 patients. Summary/Conclusion: Thirty-day all-cause mortality was significantly higher in SARS-CoV-2-infected pts with AL than in those with other hematologic diseases. Longer-term follow-up (180 days) for AL outcomes and OS will be presented.
ABSTRACT
Background: Pts with hem diseases are at high risk of COVID-19 severe course and mortality. Emerging data on risk factors and outcomes in this patient population is of great value for developing strategies of medical care. Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hem disease (both malignant and nonmalignant) and lab-confirmed or suspected (clinical symptoms and/or CT) COVID-19. Primary objective was to evaluate treatment outcomes. Primary endpoint was 30-day allcause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 486 of them eligible for primary endpoint assessment, n(%): M/F 243(50%)/243(50%), median age 56 [18-90], malignant disease in 452(93%) pts, induction phase/R/R/remission 160(33%)/120(25%)/206(42%). MTA in 93(19%) pts, 158(33%) were transfusion dependent, comorbidities in 278(57%) pts. Complications in 335(69%) pts: pneumonia (67%), CRS (8%), ARDS (7%), sepsis (6%). One-third of pts had severe COVID-19, 25% were admitted to ICU, 20% required mechanical ventilation. All-cause mortality at 30 days - 17%;80% due to COVID19 complications. At 90 days, there were 14 new deaths: 6 (43%) due to hem disease progression. Risk factors significantly associated with OS are listed in Tab 1. In multivariate analysis - ICU+mechanical ventilation, HR, 53.3 (29.1-97.8). Acute leukemias were associated with higher risk of death, HR, 2.40 (1.28-4.51), less aggressive diseases (CML, CLL, MM, nonmalignant) - with lower risk of death, HR, 0.54 (0.37-0.80). No association between time of COVID-19 diagnosis (Apr-Aug vs. Sep-Jan) and risk of death. COVID-19 affected treatment of hem disease in 65% of pts, 58% experienced treatment delay for a median of 4[1-10] weeks. Relapse rate on Day 30 and 90 - 4%, disease progression on Day 90 detected in 13(7%) pts;180-day data was not mature at the time of analysis. Several cases of COVID-19 re-infection were described. Conclusions: Thirty-day allcause mortality in pts with hem disease was higher than in general population with COVID19. Longer-term follow-up (180 days) for hem disease outcomes and OS will be presented. Univariate analysis of factors associated with lower OS.