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Objective. To assess the course and outcomes of COVID-19 in recipients of allogeneic and autologous hematopoietic stem cell transplant (HSCT). Materials and methods. The retrospective study included 44 adult recipients (allogeneic - 33 [75%] and autologous - 11 [25%] of HSCT who diagnosed with COVID-19 after transplantation. Group mostly represented by acute leukemia - 18 (41%) and lymphoma - 10 (22.7%). The median follow-up time since the development of COVID-19 was 231 days (1-818 days), after HSCT - 507.5 days (14-3723 days). Overall and progression-free survival was assessed using the Kaplan-Meier and Log-Rank method. We also evaluated the characteristics of the course of a new coronavirus infection. Results. Median time for the development of COVID-19 from the moment of HSCT was 122.5 days (-1-3490 days). Twelve patients (27.2%) were in grade 3-4 neutropenia at the time of COVID-19 diagnosis, 16 (36.4%) patients were in grade 1-2 neutropenia. Sixteen (48.4%) allo-HSCT recipients had active graft-versus-host disease (GVHD) at the time of COVID-19 development. Disease severity was mild in 19 (43.2%) and moderate in 13 (29.5%) patients. Overall, 200-day survival from the onset of COVID-19 was 78.8% (95% CI [63.1-88.4]). Anemia (p = 0.02) and thrombocytopenia (p = 0.01) significantly decrease OS in patients with COVID-19 after HSCT. Patients with GVHD at the time of COVID-19 onset had a better survival rate (p = 0.02). The timing of COVID-19 development after HSCT did not affect outcomes. Conclusions. The key points of the course of COVID-19 in HSCT recipients are the presence of cytopenia and graft-versus-host disease. Overall survival was 78.8%.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
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Background: Anti CD20/CD3 bispecific antibody glofitamab (G) demonstrated high efficacy and acceptable toxicity profile in patients with aggressive r/r B-NHL. Nevertheless, the number of patients and conditions in clinical trials is limited, which requires further study of the G safety in real clinical practice. Method(s): This study included 28 pts with r/r B-NHL who were treated with G from May 2021 to August 2022 within the Russian Named Patient Program. G was prescribed in escalated regimen: 2.5 mg D8C1, 10 mg D15C1, 30 mg D1C2-12. Anti-CD20 antibody was administrated in D1C1. Efficacy was analyzed by PET-CT (Lugano criteria). Adverse events (AEs) were graded according to NCI CTCAE 5.0. Result(s): Median age at G initiation was 50 (21-83), male/female ratio - 11/17 (39/61%). Median number of therapy lines before G was 3 (2-8). ECOG>1 at G initiation was in 7 (25%), B symptoms in 6 (21%) and bulky disease in 8 (29%) pts. Median follow-up was 6 (1-16) mo. At analysis 22 (79%) pts discontinued therapy due to PD (n=10, 36%), severe COVID-19 (n=5, 18%), therapy completion (n=5, 18%), other reason (n=2, 7%). Median number of cycles was 6 (1-12). ORR was 67% (56% CR, 11% PR). Eight pts died during G therapy including 5 (18%) pts due to PD. AEs were present in 27 (96%) pts including gr 3-4 in 14 (43%) and gr 5 in 3 (11%) pts (Table). Any grade COVID-19 was revealed in 9 (32%) pts. Three (11%) pts died due to severe COVID-19. Anti-SARS-CoV-2 antibodies were introduced in 14 (50%) pts: in 6 (21%) pts after Covid-19 and in 8 (29%) pts as a Covid-19 prophylaxis. There were no cases of severe Covid-19 after prophylaxis with antibodies. Other viral infections have also been observed: gr 1-2 VZV in 3 (11%), gr 4 CMV pneumonia in 1 (4%) pts. [Formula presented] Conclusion(s): G demonstrated high efficacy in patients with r/r B-NHL. However, the wide range of toxicities has also been demonstrated including a high rate of viral infections. Anti-SARS-CoV-2 antibodies and standard viral prophylaxis should be considered in this patient group. Legal entity responsible for the study: Liudmila Fedorova, Kirill Lepik, Olesya Smykova, Natalia Mikhailova, Marina Popova, Vladislav Markelov, Elena Kondakova, Ivan Moiseev, Alexander Kulagin. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology
ABSTRACT
Objective. To assess the course and outcomes of COVID-19 in recipients of allogeneic and autologous hematopoietic stem cell transplant (HSCT). Materials and methods. The retrospective study included 44 adult recipients (allogeneic – 33 [75%] and autologous – 11 [25%] of HSCT who diagnosed with COVID-19 after transplantation. Group mostly represented by acute leukemia – 18 (41%) and lymphoma – 10 (22.7%). The median follow-up time since the development of COVID-19 was 231 days (1–818 days), after HSCT – 507.5 days (14–3723 days). Overall and progression-free survival was assessed using the Kaplan–Meier and Log-Rank method. We also evaluated the characteristics of the course of a new coronavirus infection. Results. Median time for the development of COVID-19 from the moment of HSCT was 122.5 days (-1–3490 days). Twelve patients (27.2%) were in grade 3–4 neutropenia at the time of COVID-19 diagnosis, 16 (36.4%) patients were in grade 1–2 neutropenia. Sixteen (48.4%) allo-HSCT recipients had active graft-versus-host disease (GVHD) at the time of COVID-19 development. Disease severity was mild in 19 (43.2%) and moderate in 13 (29.5%) patients. Overall, 200-day survival from the onset of COVID-19 was 78.8% (95% CI [63.1–88.4]). Anemia (p = 0.02) and thrombocytopenia (p = 0.01) significantly decrease OS in patients with COVID-19 after HSCT. Patients with GVHD at the time of COVID-19 onset had a better survival rate (p = 0.02). The timing of COVID-19 development after HSCT did not affect outcomes. Conclusions. The key points of the course of COVID-19 in HSCT recipients are the presence of cytopenia and graft-versus-host disease. Overall survival was 78.8%. © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
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Background: In March 2020, British Columbia (BC) declared a COVID-19-related public health emergency. Measures to limit SARS-CoV-2 transmission impacted social behaviors and disrupted healthcare access. We examined client engagement in BC's province-wide, publicly-funded HIV PrEP program before and during the COVID-19 pandemic. Methods: Using de-identified data from BC's provincial PrEP Program, we describe client engagement in the 15 months pre-(Jan 2019-Mar 2020) and during (Apr 2020-Jun 2021) the pandemic, summarized by 3-month periods. Fisher's exact, Wilcoxon rank sum test, and GEE models were used to compare median number of PrEP clients (total and new) and the proportion with PrEP dispensing and HIV testing in pre-vs during pandemic periods. We also compared these outcomes in the Apr-Jun quarter of 2019 (pre-) vs 2020 (early) and 2021 (late) pandemic. Results: A total of 7300 clients engaged with the PrEP program during the 30-month study period, with median (Q1-Q3) age 33 (27-42) years, 98% cis-male, 1% trans-female, 98% gay-bisexual-MSM (gbMSM). The median (Q1-Q3) quarterly active PrEP clients increased from 4366 (4019-4677) pre-pandemic to 4754 (4683-4784) during-pandemic (p<0.001) following program expansion late 2019, but the median (Q1-Q3) number of new clients declined from 545 (504-566) to 319 (318-320;p=0.033) and the proportion of clients with HIV testing fell from 87% (87-88%) to 82% (77-82%;p<0.001). PrEP engagement in relation to the pandemic timeline (Figure) showed a transient, early pandemic drop in new initiations and medication dispensing followed by rebound. As a proportion of all active clients, new PrEP clients in the Apr-Jun quarter dropped from 14% in 2019 to 4% in 2020 (p<0.001) and remained lower at 8% in 2021 (p<0.001). A transient decrease in the proportion of new enrolees from sexual health clinics was also observed: 54% in 2019 to 44% in 2020 (p=0.017) with rebound to 55% in 2021 (p=0.784). Similarly, clients with PrEP dispensed in this quarter fell from 75% in 2019 to 56% in 2020 (p<0.001) with partial rebound to 68% in 2021 (p<0.001). HIV testing in PrEP clients fell from 87% in 2019 to 82% in 2020 (p<0.001) and remained lower at 84% in 2021 (p<0.001). Conclusion: BC PrEP program engagement declined early in the COVID-19 pandemic, with partial rebound coinciding with the easing of public health restrictions. Ongoing clinical monitoring for PrEP remains key. Continued evaluation will facilitate understanding the pandemic impact on HIV prevention programming.
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Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for oncological, hematologi-cal and non-malignant disorders. Despite global trend for a decrease of transplantation activity in view of the COVID-19 pandemic, we tried to maintain it by taking preventive measures and optimizing infection control in our center. Patients and methods This is an observational study. We collected the performance data of our transplant center from April 2020 to July 2021, i.e., during two waves of the pandemic. The main objectives were to study the influence of COVID-19 pandemic on the workflow of the HSCT center, including morbidity among employees and HSCT recipients, as well as on the transplant activity. Results The first case of COVID-19 infection in St. Petersburg was recorded on March 8, 2020. On March 30, 2020, a national lockdown had been imposed in the Russian Federation. The second wave of COVID-19 started in October 2020. Weekly screening of staff and patients was the main diagnostic tool, in addition to the governmental requirements. In sum, a total of 21702 PCR tests for SARS-CoV-2 were performed over the study period. As for July 1, 2021, 69.7% of employees became immune to the virus, due to previous COVID-19 disease, or by vaccination. In 2020, we managed to perform 419 HSCT, including 136 autologous and 283 allogeneic transplants. For comparison, 415 HSCTs were carried out in 2019, with 144 autologous and 271 allogeneic transplants. In 2020, the HSC donorship was shifted towards unrelated donors from the Russian Registry and haploidentical donors. Incidence of COVID-19 among HSCT recipients between April 2020 and July 2021 was 7.3% (n=39), being 8.6% (n=31) after allogeneic HSCT, and 4.5% (n=8) following auto-HSCT. The median age of patients with COVID-19 was 27 years (4-66). The median term for the COVID-19 onset was 68 days post-transplant (-1 to +2093). In most patients – 29 (74.3%) the HCT CI comorbidity index at the time of transplantation was 0. The stem cell source were either peripheral blood stem cells (n=22, 56.4%), or bone marrow (n=17, 43.6%). Most of the patients achieved complete remission of the underlying disease at the time of HSCT (n=30, 76.9%). The overall 100-day survival rate among HSCT recipients since the diagnosis of the COVID-19 was 79.5% (95% CI 0.609 – 0.884). The mortality rate was 20.5% (n=8). The causes of death were as follows: COVID-19 – 50% (n=4);secondary infectious complications, 25% (n=2);relapse of the underlying disease, 12.5% (n=1);hemorrhagic complications, 12.5% (n=1). The 100-day cumulative incidence of transplant-related mortality (TRM) among all HSCT recipients was 7% (95% CI 0.9 – 0.95) and 8.7% (95% CI 0.88 – 0.93) in 2019 and 2020, respectively (p=0.35). Conclusions Due to preventive measures, regular PCR screening, as well as the use of donors from the Russian Registry or haploidentical donors, we managed to maintain HSCT activity at the same level. The COVID-19 morbidity of HSCT recipients was 7.3%, their mortality rate – 20.5%. In summary, the pandemic did not affect transplant-related mortality among the HSCT recipients in our center. © Universitatsklinikum Hamburg - Eppendorf. All rights reserved.
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Background: The outcomes of relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) are very dismal with no standard of therapy. Relapsed or refractory B-NHL are heterogeneous group of lymphoproliferative malignancies with histological, cytogenetic and molecular differences, but all of them have a B-cell receptor. CD79b is a B-cell receptor component and the antibody-drug conjugate polatuzumab vedotin is an anti-CD79b antibody linked to antimitotic agent - monomethyl auristatin E. Polatuzumab vedotin in combination with bendamustine and rituximab (Pola-BR) demonstrated efficacy in patients with r/r B-NHL. Aims: To evaluate the safety and effectiveness of Pola-BR in patients with r/r B-NHL in real clinical practice. Methods: This is interim analysisof single-center prospective study evaluates efficacy and safety of Pola-BR for treatment patients with aggressive r/r B-NHL. All patients received bendamustine 90 mg/m2 on days 1 and 2, rituximab 375 mg/m2 on day 1 and polatuzumab vedotin 1,8 mg/kg on day 1 of each 21-day cycle. The PET-CT scan was performed before treatment initiation and after 2, 4, 6 cycles of Pola-BR. The responses were evaluated using Lugano 2014 criteria. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03. Results: Total of 26 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (n=18), primary mediastinal B-cell lymphoma (PMBCL) (n=7) and gray zone lymphoma (GZL) (n=1) were included. All diagnoses were histologically confirmed. Median age was 43 years (range 20-68). Most of the patients 73% (n=19) had primary chemoresistant disease. The median number of prior therapy lines was 3 (range 2-10). Five patients underwent autologous stem cell transplantation and four patients received anti-CD19 CAR-T cell therapy. At the start of Pola-BR treatment stage III-IV disease had 73% (n=19) patients and 27% (n=7) of patients had bulky disease. Median number of Pola-BR cycles was 4 (range 2-6). Nine patients (35%) completed 6 cycles of Pola-BR. Eight patients (31%) interruptedPola-BR treatment due to disease progression. The overall response rate (ORR) in the group was 61% (n=16) with 46% (n=12) of complete responses (CR) and 15% (n=4) of partial responses (PR). Two patients (8%) had stabilization of the disease as best response. The ORR in patients with DLBCL was 57% (CR 44%), in patients with PMBCL ORR was 57% (CR 43%) and one patient with GZL achieved CR. The ORR in patients with bulky disease was 14% (CR 14%) and ORR 79% (CR 58%) in patients without bulky disease. In patients with relapsed disease ORR was 86% (CR 57%) and in patients with primary chemoresistant disease ORR was 53% (CR 42%). Two patients (50%) with primary CAR-T cell therapy achieved CR. With a median follow up time 6,8 (range 2-12) month overall survival and progression free survival were 71% and 57%, respectively. During Pola-BR treatment grade 3-4 anemia, neutropenia, and thrombocytopenia developed in 19% (n=5), 42% (n=11) and 12% (n=3) patients, respectively. Other adverse events included febrile neutropenia 8% (n=2) and maculopapular rash 8% (n=2). None of the patients had peripheral neuropathy. Two patients with PR died due to Covid-19 infection. Summary/Conclusion: Our real-life data confirms that Pola-BR has an acceptable toxicity profile and it is promising method of immunochemotherapy for patients with r/r B-NHL.