COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Alveolar echinococcosis in the 21st century: An opportunistic infection?

National audienceIncreased susceptibility of experimental animals with immune suppression to alveolar echinococcosis (AE), due to Echinococcus multilocularis infection, has been known for more than 30 years, as well as the fast progression of residual AE lesions in patients with liver transplantation. However, occurrence of AE in patients with acquired immune suppression has been published as isolated cases only from the beginning of the 21st century. Based on the French Registry of Alveolar Echinococcosis cases (FrancEchino), a systematic study of AE cases in immunosuppressed patients, patients with AIDS, with cancer and malignant hematological disorders, with chronic inflammatory diseases, and with organ transplantations, has been performed. This study has confirmed the significant increase of AE cases in patients with immune suppression since 2000, compared to previous years, and of the percentage of such cases among all French AE patients, thus giving AE the status of 'opportunistic infection'. AE is most often an incidental finding in patients with a follow-up for the underlying disease. AE diagnosis is generally delayed and the treatment often erroneous because of misleading diagnostic findings, especially in patients with cancer. When the patients are symptomatic, unusual acute symptoms that simulate a liver abscess may be seen; these presenting symptoms, as well as more frequent negative serology and unusual imaging findings than in patients without immune suppression contribute to delayed diagnosis. Usual therapeutic strategy nevertheless applies to AE in immunosuppressed patients, with complete surgical resection of AE lesions whenever possible, anatomically and in the context of the underlying disease, and long-term administration of albendazole in non-operable patients. In such cases, albendazole efficacy is often excellent and fast; however, adverse effects of albendazole seem more frequent than in other patients. Complementary studies are necessary to understand whether AE occurrence in immunosuppressed patients is due to newly acquired infection or to the reactivation of dormant microscopic lesions

Clinical epidemiology of human AE in Europe

International audienc

Adrenal lymphoma: presentation, management and prognosis.

International audienceAim:This study aimed to identify the clinical, radiological and prognostic features of primary adrenal lymphoma (PAL) in order to diagnose the disease more accurately.Materials and methods:A retrospective multi-centre study was conducted on the clinical, biological and radiological features as well as the treatment and overall survival outcomes in PAL.Results:Between 1994 and 2014, 28 patients from five regions of eastern France were diagnosed with primary adrenal lymphoma. The revealing symptoms were a worsening general state (77%), weight loss (77%) and abdominal pain (42%). Biological features of PAL were almost omnipresent: increased LDH, β2 microglobulin, CRP or ferritinaemia levels. The PAL was bilateral in 20 cases (71%), adrenal insufficiency was searched for in 11 patients and found in eight (73%). CT scans showed masses of various sizes measuring up to 180 mm. On MRI, the lesions were hypointense in T1 and hyperintense in T2. When done, positron emission tomography with fluorodeoxyglucose (FDG-PET) showed locations not seen on the CT and revealed extra-adrenal locations in 70% of examinations. Adrenalectomy brought no benefit. The overall survival rate was poor (61.9% at 2 years) despite polychemotherapy.Conclusion:The clinical presentation of PAL comprised major general symptoms. Adrenal insufficiency was very common in patients with bilateral involvement but was not systematically tested. PET was an efficient examination to visualize extra-adrenal locations. The preliminary results of MRI to distinguish between PAL and adrenocortical carcinoma should be confirmed. Further studies are needed to establish an optimal strategy for the management of these primary adrenal lymphoma

Increased Incidence and Characteristics of Alveolar Echinococcosis in Patients With Immunosuppression-Associated Conditions.

International audienceBACKGROUND: An increased incidence of alveolar echinococcosis (AE) in patients with immunosuppression (IS) has been observed; our aim was to study this association and its characteristics. METHODS: Fifty AE cases with IS-associated conditions (ISCs) before or at AE diagnosis were collected from the French AE registry (1982-2012, 509 cases). There were 30 cancers, 9 malignant hematological disorders, 14 chronic inflammatory diseases, 5 transplants, and 1 case of AIDS; 9 patients had ≥2 ISCs. Characteristics of the 42 IS/AE cases and the 187 non-IS/AE cases diagnosed during the period 2002-2012 were statistically compared. RESULTS: There was a significant increase in IS/AE cases over time. Risk factors did not differ between IS/AE and non-IS/AE patients. However, AE was more frequently an incidental finding (78% vs 42%) and was diagnosed at earlier stages (41% vs 23%) in IS/AE than in non-IS/AE patients. Serology was more often negative (14% vs 1%) and treatment efficacy was better (51% regression after 1-year treatment vs 27%) in IS/AE patients. All IS/AE patients but 7 took IS drugs; 7 received biotherapeutic agents. When not concomitant, AE occurred in IS patients within a 48-month median time period. Atypical presentation and abscess-, hemangioma-, and metastasis-like images delayed AE diagnosis in 50% of IS/AE patients, resulting in inappropriate treatment. Liver images obtained for 15 patients 1-5 years before diagnosis showed no AE lesions. Albendazole efficacy was good, but 19 of 48 treated patients experienced side effects. CONCLUSIONS: Patients with immunosuppression are at increased risk for occurrence, delayed diagnosis, and progression of AE

Combination of pixantrone with rituximab, ifosfamide and etoposide in relapsed/refractory aggressive non-Hodgkin lymphoma. Results from a phase II LYSA study (PIVeR)

International audienceIntroduction: The prognosis of patients with relapsed/refractory aggressive non-hodgkin lymphoma (R/R aNHL) remains poor with conventional immunochemotherapies. Pixantrone is an aza-anthracenedione agent designed to improve the efficacy and reduce the toxicity associated with anthracyclines and anthracenediones. In this context, we conducted a phase II trial combining pixantrone with ifosfamide, etoposide and rituximab (PIVeR) in R/R aNHL. The primary objective was to assess the efficacy measured by the overall metabolic response (OMR) rate after 2 cycles.Methods: Patients were eligible if they had a histologically proven CD20+ aNHL (de novo diffuse large B-cell lymphoma (DLBCL) or transformed low-grade NHL or grade 3B follicular lymphoma). R/R disease was defined as follows: (1) autologous stem-cell transplantation (ASCT) eligible patients who failed to achieve a CR after at least one salvage therapy, (2) patients in first relapse after ASCT or (3) patients not eligible for ASCT who failed to achieve a CR after at least one prior treatment. First response evaluation by PET-scan was performed after 2 cycles. Responders could then proceed, if eligible, to ASCT or CAR T-Cells therapies after a third optional cycle. Others responding patients were treated with four additional cycles.The study was designed in order to detect an OMR rate increase from 40% to 55%, assuming an 80% power at a 5% (1-sided) significance level using a two-stage phase II design. A total of 84 evaluable patient was expected.Results: Between March 2018 and December 2021, 74 patients were enrolled. The median age was 70 y (range 35–87). The majority of the patients had a diagnosis of de novo DLBCL (85.1%) and 43.2% were primary refractory.After 2 cycles, the OMR rate was 59.5% (90% CI = 49.2%–69.1%) with 18.9% complete metabolic response (CMR). A total of 44 patients completed the treatment. At the end of treatment, the OMR rate was 36.5% with 24.3% CMR. With a median follow-up of 16.6 mo, median PFS and OS were respectively 3.7 mo (95% CI = 2.6–5.6) and 19.2 mo (95% CI = 11.9–36.5). Three patients had an ASCT and 16 were treated with CAR T-Cells. For patients treated with CAR T-Cells, the OMR rate after CAR T-Cells was 31.3% and median OS was not reached.A total of 53 patients (71.6%) reported at least one AE. The most frequent grade 3–4 AEs were neutropenia (28.4%), thrombocytopenia (18.9%) and anemia (17.6%). Cardiac AEs occurred in 6 patients (11.3%) and 5 (9.4%) had a grade 3–4 heart failure. Serious AEs occurred in 30.9% of the patients, leading to treatment discontinuation in 3 cases.Conclusion: The primary objective of this trial was met with a high OMR rate of 59.5% after 2 cycles of the PIVeR regimen. The safety profile appeared manageable with few grade 3–4 cardiac AEs. Based on these results, the use of pixantrone in salvage treatment of R/R aNHL should be further evaluated, in particular in the context of bridging therapy before CAR T-Cells

Health-related quality of life profile of newly diagnosed patients with Hodgkin and non-Hodgkin lymphomas: A real-world study including 3922 patients from the French REALYSA cohort.

International audienceIntroductionConsidering the notable advances made in the treatment of lymphoma, assessment of health-related quality of life (HRQoL) of lymphoma patients has become a critical aspect to consider both in clinical research and routine practice. However, there is paucity of information about lymphoma specific HRQoL profile at diagnosis.Patients and methodsHRQoL at diagnosis was assessed for 3922 adult patients with newly diagnosed high-grade (HG) (n = 1994), low-grade (LG) (n = 1053) non-Hodgkin (NHL) and Hodgkin (HL) (n = 875) lymphomas included in REal world dAta in LYmphoma and Survival in Adults (REALYSA, NCT03869619), a prospective non-interventional multicentric cohort in France. Disease-specific HRQoL aspects were assessed with three validated EORTC questionnaires, namely, the QLQ‐NHL‐HG29, the QLQ-NHL-LG20 and the QLQ-HL27, for patients with NHL-HG, NHL-LG and HL, respectively.ResultsWe confirmed the high-level of completion of these questionnaires in REALYSA cohort, ranging from 84 % for QLQ-HG29 to 88 % for QLQ-HL27. The proportion of patients with impaired global health status was as follows: T-cell NHL, 67 %; diffuse large B-cell (DLBCL), 62 %; Burkitt, 61 %; HL, 53 %; marginal zone, 49 %; mantle cell, 48 %; follicular, 47 %. Multivariable regression analyses for DLBCL, follicular and HL showed that gender, performance status and B symptoms were independently associated with all HRQoL dimensions. However, a variable effect of age and stage were observed among these three subtypes.ConclusionsA comprehensive analysis was made describing the HRQoL profile of newly diagnosed patients with different types of lymphomas. Our data may help to enhance the interpretation of HRQoL results in future studies using the recently validated EORTC lymphoma specific questionnaires

Efficacy of anti‐PD1 therapy in relapsed or refractory NK/T cell lymphoma: a matched cohort analysis from the LYSA

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Outcome of large B-cell lymphoma patients treated with tafasitamab plus lenalidomide either before or after CAR-T-cells.

International audienceTafasitamab plus lenalidomide (TAFA-LEN) treatment relevance pre- or post-anti-CD19 CAR T-cell is currently debated. We analyzed large B-cell lymphoma patients in the DESCAR-T registry treated with axi-cel or tisa-cel in ≥3rd line (L3+) and TAFA-LEN before (n=15, 'TL-pre-CAR-T' set) or directly after (n=52, 'TL-post-CAR-T' set) CAR T-cell. We compared TAFA-LEN v. other treatments using inverse probability weighting in the TL-post-CAR-T set. In the TL-post-CAR-T' set, the median follow-up duration (mFUD) was 7 months, and the median progression-free survival, overall survival and duration of response since the 1st treatment for progression (mPFS2/mOS2/mDOR2) were 3, 4.7 and 8.1 months, respectively. The best overall response rate (bORR) and best complete response rate (bCRR) after TAFA-LEN were 13.5% and 7.7%, respectively. Outcomes were better for patients who relapsed >6 months after CAR T-cell (mPFS2: 5.6 vs. 2 months, p=0.0138; mOS2: not reached vs. 3.8 months, p=0.0034). bORR and bCRR between TAFA-LEN and other treatments were 20.6% vs. 24.9% and 11.6% vs. 15.6%, respectively. Outcomes were similar between TAFA-LEN and other treatments (mPFS2: 2.9 [2-2.6] vs. 2.4 [1.5-4.2] months, p=0.91; mOS2: 3.3 [1.8-6.4] vs. 5.5 [4.4-6.3] months, p=0.06). In an exploratory analysis of the TL-pre-CAR-T set (mFUD since CAR T-cell: 2.8 months), the median TAFA-LEN treatment duration prior to CAR-T was 3.7 months and no patients were reported to become CD19 negative. The bORR, bCRR, 6-month PFS and OS rates after CAR T-cell infusion were 45.5%, 36.4%, 20.1% and 58.2%, respectively. Neither TAFA-LEN nor comparative salvage treatments improved outcomes of patients who relapsed after CAR T-cell