ABSTRACT
Introduction:Recently there has been a renewal of therapeutic tools for the treatment of lymphoid neoplasms to increase the antitumor efficacy and reduce the toxicity generated by conventional chemotherapies, which adds to the intrinsic immunological dysfunction of the disease itself. To date, few data are published about infection risk of these new drugs, and the need for infectious prophylaxis is unknown. The aim of the study is to analyze the infectious complications in patients with LPD treated with monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab and pembrolizumab), BTK inhibitors (ibrutinib, acalabrutinib) and PI3K inhibitors (idelalisib). Methods: Multicenter retrospective study in patients with LPD treated with targeted therapies (single agents or combination) in 18 Hematology centers in Spain, from the time of their commercial availability to March 2020. Patients in clinical trials were excluded as well as patients with active infections at the beginning of treatment. Results:During the study period, 380 patients were included.Baseline characteristics of the entire cohort are shown in Table 1.Median follow-up was 17.3 months (range 0-103), the longest follow-up corresponding to CLL patients (24 months, range 0-98) and the shortest to LBCL (5 months, range 0-25). Median exposure to target drugs was 8 months (range 0-72).Ibrutinib was administered to 219 patients(1 FL, 147 CLL, 27 MCL, 10 DLBCL, 1 TL and 32 WM, 1 HL),Brentuximab to 49(31 HL, 14 TL and 4 DLBCL) andIdelalisibto 35 patients (16 affected by chronic lymphocytic leukemia - CLL, 15 FL and 1 DLBCL, 1 WM, 1MCL, 1HL).Obinutuzumabcombinations were used in 10 (6 CLL, 3 FL, 1 MCL) and 5 HL patients (of which 4/5 underwent previous BMT) receivedNivolumab. A total number of 237 infectious events occurred in 148/380 patients (38.9%), 39% of which were grade 3 and 54/148 (36.4%) experienced 2 or more infective episodes: of those 54, 21 (38%) had underwent 3 or more lines of therapy and 28 (51%) had hypogammaglobulinemia. Hospitalization was required in 59.2% events. A bacterial cause of infection was reported in 40% of cases, and viral in 16%, including 11/237 (4,6%) SARS-CoV-2 infection. Invasive fungal infection (IFI) occurred in 3.3% (8/237). Noteworthy, no case of PJP was identified. Lung was the most frequent site of infection in 24% of cases (57/237) while the upper respiratory tract was involved in 17% of events (41/237). Urinary tract infections were diagnosed in 10% (24/237). Other sites involved were skin and soft tissue 7%, gastrointestinal tract 5,4%, bloodstream infections 3% and catheter related infections 2,5%. Considering drugs individually, 86 patients that receivedIbrutinib(39.2 %)experienced a total of 137 infectious episodes: 30% bacterial, 19% viral, 5% fungal and 45% clinical and image-based infections;the 17(34.6%of those who received Brentuximab, experienced a total of 16 infectious episodes: 56% bacterial, 37.5% viral infections and one catheter-related sepsis. Of those who receivedIdelalisib,18 (51.4%)experienced a total of 28 episodes: 42% bacterial, 14% viral and 7% fungal. Four patients treated withObinutuzumabcombinations (40%) experienced one infection during treatment (25% bacterial and 75% viral). Only one patient treated withNivolumabexperienced more than three infections, he was also under corticosteroid treatment. Focusing on IFI (Table 2): 7/8 infections were identified in CLL patients, 6 out 7 being on ibrutinib treatment and 1/7 on Idelalisib.Aspergilluswas the fungus most frequently isolated. The targeted drug was discontinued temporarily in 4 patients and indefinitely in 3. Twenty three (6%) patients died due to infection in our series. Conclusions: 1. We identified 38.7% infections in our LPD patients treated with targeted drugs, with a median drug-exposure time of 8 months (range 0-72), with a non-negligible incidence of bacterial infections. 2. The highest rates of infection were found in patients treated with with Idelalisib and Ibrutinib (51.4% and 39.2% respectively). 3. IFI (3.3%) occurr d with low frequency, mostly in CLL patients during ibrutinib treatment, leading to its temporal discontinuation in most of the cases. 4. No case of PJP was identified in our cohort. 5. An analysis to determine risk factors for infection and the optimal monitoring and prophylaxis for these patients is ongoing. [Formula presented] Disclosures: Hernandez-Rivas:Janssen:Membership on an entity's Board of Directors or advisory committees;Abbvie:Membership on an entity's Board of Directors or advisory committees;Roche:Membership on an entity's Board of Directors or advisory committees;AstraZeneca:Membership on an entity's Board of Directors or advisory committees;Gilead:Membership on an entity's Board of Directors or advisory committees;Celgene/BMS:Membership on an entity's Board of Directors or advisory committees;Rovi:Membership on an entity's Board of Directors or advisory committees.Lopez-Guillermo:novartis:Consultancy;celgene:Consultancy, Research Funding;roche:Consultancy, Research Funding;gilead:Consultancy, Research Funding.
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.