IgM Multiple Myeloma Presenting With Diarrhea

Introduction: IgM Multiple Myeloma (MM) is a rare subtype of MM consisting of <1% cases of MM. It is distinguished from Waldenstrom Macroglobinemia, which also produces IgM, by the absence of somatic mutation MYD88. We present a patient with a chief complaint of diarrhea which unknowingly led to his hematological diagnosis Case Description/Methods: A 64 year old male with RA-SLE overlap syndrome on steroids, and recent COVID19 pneumonia, had presented with 5 episodes of watery diarrhea every day and 40 Ib weight loss within 2 months. CT revealed small bowel enteritis and stool studies, including C. diff, cultures, ova and parasites were negative. Diarrhea persisted despite antibiotics, therefore an EGD and Colonoscopy were performed which showed duodenal lymphangiectasia and a normal colon. Duodenal biopsy revealed eosinophilic deposits in the villous lamina propria which stained for IgM and stained negative under congo red ruling out amyloidosis. SPEP and a bone marrow biopsy revealed monoclonal IgMspikes and plasma cells in the bone marrow suggesting MMalong with a co-existing population of CLL. Next-generation sequencing was negative forMYD88, supporting IgM MM instead of Waldenstrom. He developed a protein-losing enteropathy with dramatic hypoalbuminemia (albumin 0.9) and lower extremity edema and DVTs. He was started on chemotherapy and frequent albumin infusions. His diarrhea completely resolved, however not in time, as his other medical comorbidities lagged behind and he developed anasarca and continued to deteriorate. Discussion(s): Plasma cell dyscrasias such as IgM MM or more commonly Waldenstrom have rarely been reported to cause GI symptoms. GI involvement can include direct GI infiltration of plasma cells, IgM deposition, or the finding of a plasmacytoma. It has been speculated that IgM deposits can lead to interstitial viscosity and obstructive lymphangiectasia leading to diarrhea and a protein-losing enteropathy as in our patient. Protein loss has led him to have hypoalbuminemia and possibly loss of antithrombotic proteins that have caused DVTs. Few case reports have suggested that treating the underlying cause with chemotherapy stops diarrhea entirely. Although our patient's diarrhea ceased, we believe that it was not in time for him to entirely recover from the later complications of the disease. We hope that this case can help clinicians to attempt prompt treatment of patients when they find GI specimens showing IgM deposits and they suspect a plasma cell dyscrasia.

Humoral and cellular immune response to second and third severe acute respiratory syndrome coronavirus 2 mRNA vaccine in patients with plasma cell dyscrasia.

BACKGROUND: The recently developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine has a short history of use and further information is needed regarding its efficacy, especially in immunocompromised conditions, such as plasma cell dyscrasia (PCD). METHODS: We retrospectively measured serum SARS-CoV-2 antibodies against the spike protein (S-IgG) after the second and third mRNA vaccine doses (doses 2 and 3, respectively) in 109 patients with PCD. We evaluated the proportion of patients with an adequate humoral response (defined as S-IgG titers ≥300 antibody units/mL). RESULTS: Although active anti-myeloma treatments prior to vaccination had a significantly negative impact on adequate humoral response, specific drug subclasses including immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies were not negatively associated, except for B-cell maturation antigen-targeted therapy. Dose 3 (booster vaccination) led to significantly higher S-IgG titers and more patients acquired an adequate humoral response. Furthermore, evaluation of vaccine-induced cellular immune response in patients using T-spot Discovery SARS-CoV-2 kit, revealed an enhanced cellular immune response after Dose 3. CONCLUSIONS: This study highlighted the significance of booster SARS-CoV-2 mRNA vaccination in patients with PCD with respect to humoral and cellular immunity. Moreover, this study highlighted the potential impact of certain drug subclasses on vaccine-induced humoral immune response.

IS IT SAFE FOR OUR PATIENTS TO COME OUT?

Background: Vaccination against COVID-19 commenced in England in December 2020, most haematology patients iwere included in the first wave as they are identified as extremely vulnerable. A second dose was administered 12 weeks after the initial dose, and booster doses became available in September 2021. Severely immune compromised patients started to be contacted in December 2021 to offer them a fourth dose of vaccine. With the availability of treatments there arose a need for early confirmation of presence or absence of antibodies against COVID-19 and testing for antibody was introduced into routine practice for patients about to commence chemotherapy, or those who had yet to complete the four-dose protocol. On the 1st of March most restrictions imposed during the pandemic were removed, in the expectation that the majority of people would have protective antibodies from vaccination. Aims: Over a period of six months from October 2021 to February 2022 we tested 90 patients attending routine haematology clinics, with a number of conditions, mainly malignancy under follow-up or recieving treatment. We reviewed the results of these tests, to assess degree of protection Methods: Retrospective analysis of all requests for SARS-Cov antibody tests carried out in our patient populations. Results: There were 55 males, and 35 females, with an average age of 65y (range 24-90) The majority attended clinic for management of haematological malignancy (Plasma cell disorders, Chronic Leukaemia, Lymphomas) with a smaller number of patients being managed for congenital or immune conditions. Diagnosis No detectable antibody Antibody<500 units Antibody > 500 units (Table Presented) Summary/Conclusion: Despite early availability of vaccines, and delivery of more than two doses to the majority of our patients, only half our patients had significant antibody response, and almost one quarter still had no detectable antibody. Although the number of new cases is reducing, in the vicinity of our Hospital there were 483 new cases per 100,000 on the last day of February, and during the six months of this study two fully vaccinated patients with CLL with no detectctable antibody died in Hospital with covid-19 pneumonitis. For some haematology patients particulalry those with CLL it is still not safe to come out.

SARS CoV-2 vaccine seroconversion and infection rates in patients on active cancerdirected therapy

Background: Cancer-directed therapy, including cytotoxic chemotherapy and immunotherapy, is a known risk factor for decreased SARS-CoV-2 seroconversion after vaccination, as a result of impaired viral immunity. Outcomes of COVID-19 infection are worse in patients on active treatment, especially those with hematologic malignancies or undergoing stem cell transplantation. The association between cancer subtypes and seroconversion rates is not well established. The goal of this study was to investigate predictive factors for SARS CoV-2 seroconversion and infection. Methods: We reviewed the electronic medical records of all patients with documented SARS CoV-2 antibody levels (between 7/2020-8/2021) in one of the largest integrated health systems in Pennsylvania. Patients who had a diagnosis of hematologic or solid malignancy, were on active treatment (including adjuvant), and had received ≥1 dose of an FDA authorized SARS CoV-2 vaccine were included. Data regarding SARS CoV-2 serology, vaccination, cancer history, and treatment regimens for each patient were collected systematically. Positive serology (reflecting seroconversion) was defined as any value ≥0.8 units/mL. Logistic regression analyses were used to examine predictors of seroconversion. Data was analyzed using SPSS v26 (IBM Corp). Results: A total of 292 patients met the inclusion criteria. Hematologic malignancy was present in 80.5% of the patients and solid tumors in 26.7%. Active disease was present in 71.6% of the cohort. Two vaccine doses were given to 92.5% of the patients and 54.8% of patients received a booster dose (95.2% received mRNA vaccines, either BNT162b2 (Pfizer BioNTech) or mRNA-1273 (Moderna)). A history of COVID-19 infection was present in 15.1% of patients, 59.1% of whom were seropositive. Rates of seroconversion were equivalent in those who received the BNT162b2 (70.2%) or mRNA-1273 (70.9%) vaccines. Seroconversion rates were 69.9% in those with active disease, 81.9% without evidence of disease, and varied by diagnosis as follows (indolent B-cell lymphoma 73.3%, aggressive B-cell lymphoma (BCL) 55.9%, plasma cell dyscrasia 80.1%, CLL 39.5%, myeloid disorder 90.2%, lung cancer 80%, breast cancer 80%, GI cancers 81.3%, and GU cancers 76.9%). On univariate regression, receipt of treatment for CLL (OR 5.79, 95% CI 2.92-11.48, p < 0.001) and aggressive BCL (OR 2.44, 95% CI 1.17-5.09) were predictive of negative serology. Results were not changed on multivariate regression when adjusted for age and active treatment. Conclusions: In this retrospective cohort of vaccinated patients on cancer-directed therapy, treatment for aggressive BCL and CLL was associated with negative seroconversion. In addition, more breakthrough infections occurred in seropositive patients, suggestive of underlying immunodeficiency related to treatment or decreased vaccine efficacy despite formation of virus-specific antibodies.

Retrospective analysis of vaccine antibody titers in patients with different stages of monoclonal plasma cell disorders

Background: Infections occur with up to twofold increased risk in patients with monoclonal gammopathy of undetermined significance (MGUS) and tenfold increased risk in multiple myeloma (MM). To reduce risk, revaccination following autologous hematopoietic cell transplantation (AHCT) is recommended to restore humoral immunity. We have previously shown that vaccine titers after AHCT have prognostic significance. In the COVID era, reliable clinical data about antibody titers is relevant yet scarce. We investigated the significance of different vaccine titers in newly diagnosed patients in different stages of the disease. Methods: The study population comprised of 77 patients with MGUS, smoldering multiple myeloma (SMM) and MM who were seen at a tertiary cancer center from 2018- 2022. All patients had antibody titers (B. pertussis, Diptheria, H. Influenzae B, Hepatitis, Influenza, Meningitis, Mumps, Rubeola, Rubella, Poliovirus, S. pneumoniae, Varicella Zoster and Tetanus) tested at the time of diagnosis, prior to start of treatment if indicated. Titers were interpreted in accordance with the manufacturers' recommendations. Patient characteristics were compared using the Kruskal- Wallis and Fisher's exact tests. Associations with % titer positivity were evaluated using the Kruskal- Wallis test. Results: There was significant difference in antibody titer positivity between the different patient groups (51.4% in MGUS, 40.5% in SMM and 34.2% in MM) (p < 0.001). There was no difference in antibody titer positivity depending on age, sex or race. Among individual pathogens, there was a significant difference between the three groups in regards to titers for Diphtheria, Mumps, Poliovirus 3, Strep pneumoniae 19, Strep pneumoniae 56 and Varicella Zoster. Conclusions: Antibody titers for vaccine preventable diseases are significantly different between patients with MGUS, SMM and MM at the time of diagnosis, with MGUS having the highest and MM having the lowest positivity. Patient related factors such as age, sex or race were not associated with antibody titer positivity. Current guidelines for revaccination are not extended to patients with MGUS and SMM and can be considered in prospective trials.

COVID vaccine immune response in patients with plasma cell dyscrasia: A systematic review

Background: The defective immune system in plasma cell dyscrasia places patients at a higher risk of developing a severe infection, which is one of the leading causes of death in such patients. In an era of a global pandemic, it is essential to protect them against COVID-19, but fewer effective plasma cells lead to a suboptimal response to vaccines. There is still a lack of evidence whether the seroconversion is truly clinically relevant and if patients with plasma cell disorders would benefit from frequent boosters to maintain antibody levels. Methods: Online databases including PubMed, CINAHL, Ovid, and Cochrane were searched (January 11th, 2022), following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Only articles published in the English language were included. s, case reports, and case series were excluded. Out of 40 studies, 5 articles were selected for a systematic review. Results: In all 5 studies (N=654), seroconversion post-vaccination was used as a positive response to COVID-19 vaccination. Although patients with plasma cell disorders had a lower seroconversion rate compared to controls, the overall percentage was substantial and ranged between 23-95.5%. Amongst patients on active therapy, lower seroconversion rates were seen in patients on a CD-38 inhibitor, ranging from 20.2-92.1% (N=174). Also, a significantly lower percentage was recorded in patients above 65 years and those who have been treated with multiple therapies previously. Better seroconversion rates were seen in mRNA vaccines compared to J&J. Conclusions: Variable seropositive rates are seen in patients with plasma cell dyscrasias, lower rates are reported in patients on active therapy, CD-38 targeting therapy, and elderly patients. Hence, these patients should receive a 4 shot series.

Low clinical protective response to SARS-CoV-2 mRNA COVID-19 vaccine in patients with multiple myeloma.

We conducted a prospective, three-center, observational study in Japan to evaluate the prevalence of seropositivity and clinically protective titer after coronavirus disease 2019 vaccination in patients with plasma cell dyscrasia(PCD). Two-hundred sixty-nine patients with PCD [206 symptomatic multiple myeloma (MM)] were evaluated. Seropositivity was observed in 88.7% and a clinically protective titer in 38.3% of MM patients, both of which were significantly lower than those of healthy controls. Patients receiving anti-CD38 antibodies had much lower antibody titers, but antibody titers recovered in those who underwent a wash-out period before vaccine administration. Older age (≥65), anti-CD38 antibody administration, immunomodulatory drugs use, lymphopenia (<1000/µL), and lower polyclonal IgG (<550 mg/dL) had a negative impact for the sufficient antibody production according to multivariate analysis. Patients with clinically protective titer had a significantly higher number of CD19+ lymphocytes than those with lower antibody responses (114 vs. 35/µL, p = 0.016). Our results suggested that patients with PCD should be vaccinated, and that the ideal protocol is to temporarily interrupt anti-CD38 antibody therapy for a "wash-out" period of a few months, followed by a (booster) vaccine after the B-cells have recovery.

Presence of monoclonal components in SARS-CoV-2 patients: Preliminary data

Introduction: electrophoresis of serum proteins (EF) is indicated for the identification and monitoring of monoclonal components (CM). It has been shown that interleukins play a role in the differentiation of B cells in plasma cells producing immunoglobulins;it has been also demonstrated that COVID-19 patients show a higher prevalence of CM in comparison to the general population. The aim of this work is to retrospectively evaluate the presence of CM in patients hospitalized with COVID-19, compared to a population of patients admitted in non-COVID-19 wards. Methods: EF was performed in the two groups of patients (COVID positive and negative) using capillary electrophoresis. Patients with previous plasma cell dyscrasias have been excluded. Results: the results show that in the COVID positive group, the incidence of CM is statistically higher compared to the COVID negative group (39.7% versus 13.3%). In one patient, the CM was no longer detectable when the swab became negative. Conclusions: the study confirmed that the viral infection produces detectable CM, probably transitory as shown by a case index. The pathogenesis of the phenomenon could be explained by the cytokine stimulus on B cells and by the interaction of the virus with the lymphocyte ACE 2 receptor. Larger studies are needed to confirm the presented data.

Humoral SARS-CoV-2 response in asymptomatic precursor plasma cell dyscrasia patients: IMPACT study results

Introduction: Patients with hematologic malignancies, including multiple myeloma (MM), experience worse SARS-CoV-2 infection outcomes and sub-optimal vaccine responses. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) precede MM and affect ∼5% of individuals age >=50. We previously showed that individuals with MGUS and SMM exhibit immune dysregulation. Here, we investigate the immune response to SARS-CoV-2 vaccination in these asymptomatic but potentially immunocompromised individuals. Methods: The IMPACT study (IRB #20-332) is a prospective study at Dana-Farber Cancer Institute in collaboration with MMRF, which enrolled individuals nationwide with a diagnosed plasma cell dyscrasia and healthy individuals. As of October 2021, 3,005 individuals completed a questionnaire regarding prior infection or vaccination. We obtained 1,350 blood samples from 628 participants and analyzed anti-SARS-CoV-2 IgG antibody titer by ELISA. Results: 2,771 (92%) participants were fully vaccinated (2 doses BNT162b2 or mRNA-1273;1 dose Ad26.COV2.s), 269 (9%) had received a 3rd mRNA vaccine dose, and 234 (8%) were unvaccinated. 1,387 (46%) and 1,093 (36%) participants received mRNA vaccines (BNT162b2 and mRNA-1273), and 139 (5%) participants received an adenovirus vector vaccine (Ad26.COV2.S). 34 (1%) individuals reported SARS-CoV-2 infection after full vaccination. We measured antibody titers in 201 MGUS, 223 SMM, 40 smoldering Waldenstrom macroglobulinemia (SWM), 64 MM, and 100 healthy controls. Multiple linear regression model estimated the association between various clinical variables and post-vaccination antibody titers. As previously reported, having MM was associated with low antibody titer (p < 0.001). Of note, having SMM, regardless of risk stratification by 2/20/20 criteria, was also associated with low antibody titers, indicating that even low-risk SMM patients have a poor response to vaccination. MGUS and SWM diagnoses were not significantly associated with antibody titers. Additionally, male sex (p < 0.010), elapsed time after vaccination (p < 0.001), and BNT162b2 vaccine (p < 0.001) were associated with low antibody titers. SARS-CoV-2 infection prior to vaccination was associated with high antibody titers. We identified 25 patients (6 MGUS, 10 SMM, 2 SWM, 7 MM) who submitted blood samples after both the 2nd and 3rd dose. In these patients we observed a significant increase in antibody titer after a 3rd dose (p = 0.002). We also observed that antibody titers of patients after a 3rd dose (13 MGUS, 12 SMM, 2 SWM, 31 MM) were comparable to that of healthy individuals after a 2nd dose (p = 0.833). Conclusion: Our data indicates that suboptimal response to SARS-CoV-2 does not only occur with MM and cancer patients receiving therapy but also in precursor asymptomatic patients including low-risk SMM.

Single-cell RNA-sequencing for immune profiling of SARS-CoV2 vaccine response in healthy individuals and patients with precursor plasma cell malignancies

Introduction: Patients with hematological malignancies exhibit inferior response to SARS-CoV2 vaccination, compared to healthy individuals, however little is known about patients with precursor hematological malignancies and the cellular underpinnings of vaccination response. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM) are plasma cell premalignancies that precede Multiple Myeloma (MM) and exhibit signs of immune dysregulation;they affect approximately 5% of the population over 50 years of age, who remain largely undiagnosed, due to lack of screening. In November 2019, we launched the IMPACT study to characterize the immune response to SARS-CoV2 vaccination in patients with plasma cell dyscrasias and healthy individuals. Methods: We performed single-cell RNA-sequencing on 224 peripheral blood mononuclear cell samples drawn from 118 IMPACT (IRB #20-332) participants with MGUS (n=20), SMM (n=48), or MM (n=24), as well as healthy individuals (n=26). Samples were collected before vaccination and after 2 doses of BNT162b2 (Pfizer-BioNtech) (n=123), mRNA-1273 (Moderna) (n=83) or 1 dose of Ad26.COV2.S (Janssen) (n=14). Results: Overall, we sequenced 2,025,611 cells from 224 samples of 118 patients with MGUS, SMM, MM and healthy individuals pre- and post-vaccination for SARS-CoV2, and profiled 553,082 T-cells, 95,392 B-cells, 74,394 NK cells, 195,371 Monocytes, and 35,236 Dendritic cells (DC). We identified activated clusters of B-cells, NK cells and DCs expressing genes such as CD83, CD69, CXCR4, and genes related to the NF-kB and AP-1 pathways. We compared cell type abundances pre- and post-vaccination within each participant population and found that activated CD83+ cells significantly increased post-vaccination in healthy individuals and patients with MGUS (paired t-test, q < 0.1), but not in patients with SMM or overt MM. At baseline, patients with SMM and MM had significantly fewer memory B-cells and significantly more cytotoxic T-cells and NK cells, compared to healthy individuals (Wilcoxon, q < 0.1), which could partly explain the differences observed post-vaccination. Patients with MM also had significantly higher levels of tolerogenic IL-10-expressing DCs (DC10) at baseline (Wilcoxon, q < 0.1), which could be dampening antigen-specific T-cell responses. Conclusion: We identified a significant expansion of activated B-cell, NK cell and DC subpopulations expressing CD83, CD69 and CXCR4, following vaccination in healthy individuals and patients with MGUS, but less so in patients with SMM and overt MM. Our results provide insight into the cellular mechanisms of immune response to SARS-CoV2 vaccination in healthy individuals and patients with precursor plasma cell malignancies and suggest that asymptomatic individuals with SMM may exhibit inferior response to vaccination.

Patients with plasma cell disorders retain their humoral response to COVID-19 vaccination following autologous stem cell transplant but falling titres emphasise the importance of re-vaccination

There is increased infection risk at the time of autologous stem cell transplantation (ASCT) including for patients with plasma cell disorders (PCD), therefore preventing infection with COVID-19 vaccination in this vulnerable group is key. However, patients with PCD have been shown to mount suboptimal responses to COVID-19 vaccination. A clinical audit of serological response to COVID-19 vaccination before and after ASCT was undertaken, to observe how antibody titres change during this period. Antibodies to the SARS-CoV-2 spike protein were measured using the Elecsys Anti-SARS-CoV-2S assay (Roche diagnostics) in 88 patients who underwent ASCT for PCD at the University College London Hospital NHS Foundation Trust between December 2020 and September 2021. Pre-ASCT antibody titres were measured following first or second vaccine and following ASCT. The majority ( n = 76) had no prior history of COVID-19 infection, and four of this cohort declined vaccination. In those who received one vaccine pre-ASCT ( n = 21), 76% seroconverted with a median titre of 11.3 3 U/ml (IQR 1.5-62.6). In those who received two doses pre-ASCT ( n = 51), 97% seroconverted with a median titre of 494 U/ml (IQR 190.5-1681). In those who received two doses pre-ASCT, anti-S antibodies were detected in the immediate post-ASCT setting, with titres of 373 U/ml (median, IQR 40.6-2326) measured less than or equal to 28 days (median 15 [6-25]) post-ASCT, and 170 U/ml (IQR 55-604) at more than 28 days (median 85 [32-125]) post-ASCT. Patients who received one dose pre-ASCT had lower median titres of 36.5 U/ml (IQR 12.6-1310) measured less than or equal to 28 days (median 15 [12-22] post-ASCT and 7.7 U/ml (IQR 2.9-23.8) at more than 28 days (median 85 [40-104] post-ASCT. Antibody levels declined over time, but patients who had received two vaccines pre-ASCT maintained higher titres post-ASCT compared to those who had received one dose, emphasising the importance of COVID-19 vaccination prior to ASCT. Our patients are advised to be re-vaccinated against COVID-19 3 months after ASCT, and antibody response following re-vaccination was measured in a subgroup ( n = 14). Those who were previously un-vaccinated did not seroconvert following one dose. However, antibody titres in those who had received either one or two vaccines ( n = 12) prior to ASCT increased from 32.4 U/ml (median, IQR 13.4-1082) post-ASCT to 431 U/ml (median, IQR 15.33-2500) following re-vaccination. Those who had received two vaccines pre-ASCT ( n = 2) achieved higher titres than those who had received a single dose. In conclusion, we demonstrated how protective titres fall during the patient's journey through ASCT and our repeated interactions with them. Despite this, patients vaccinated prior to ASCT maintain some level of measurable antibody immediately post-ASCT, which is encouraging as patients are considered most vulnerable to infection during this period. Titres were also boosted effectively after one dose of re-vaccination, compared to those never vaccinated. Current guidance is for adult patients who have undergone ASCT to be considered 'never vaccinated' against COVID-19, in line with pre-COVID-19 re-vaccination practice, and to receive a three-dose primary course followed by a booster vaccination post-ASCT. We must facilitate and encourage our patients to be vaccinated prior and after ASCT in this rapidly changing landscape, especially in context of the spread and evolution of a potentially more transmissible virus. (Table Presented).

CLINICAL PROFILE AND THE OUTCOME OF COVID-19 IN PATIENTS WITH HEMATOLOGICAL MALIGNANCY: A SINGLE CENTRE EXPERIENCE

Objective: In the present study, we are reporting the clinical profile;and outcomes of COVID-19 in patients with hematological malignancy at tertiary care hospitals. Methods: Data from laboratory-confirmed 40 COVID-19 patients diagnosed between January 1, 2021 and July 31, 2021, were analyzed retrospectively. All COVID-19 patients with hematological malignancy (n=40) were included in the study. Results: In the present study, a total of 40 patients were included. Of 40, 25 (62.5%) were males, and 15 (37.5%) were females. The median age in this study was 43 years (Range, 8–70). Of these 40 patients, acute myeloid leukemia was the most common malignancy 11 (27.5%), followed by acute lymphoblastic leukemia 9 (22.5%) than non-Hodgkin lymphoma 5 (12.5%), plasma cell dyscrasia 4 (10%), chronic myeloid leukemia 4 (10%), chronic lymphocytic leukemia 3 (7.5%), acute promyelocytic leukemia 2 (5%), chronic myelomonocytic leukemia 2 (5%). Mean hemoglobin was (8.04 g/dl), white blood cell count was (10.14×109/l), platelet count was (77.7×109/l) creatinine was (0.86 mg/dl), bilirubin was (1.24 mg/dl). The overall case-fatality rate was 8 (22.5%). Conclusion: Patients with hematological malignancy are immunocompromised, and our study reveals that there is an increased case fatality rate among these patients. Hence, physicians should be aggressive in the management of COVID-19 patients with hematological malignancy.

Serological response to the BNT162B2 mRNA or ChAdOx-nCOV-19 COVID-19 vaccine after first and second doses in plasma cell disorder patients: Influence of host and disease factors

Background Plasma cell disorders (PCD) are at risk of inadequate immune responses to COVID-19 vaccines due to recognised humoral and cellular immune dysfunction which is multi-factorial and related to host and disease factors. With an estimated risk of 33% mortality from contracting COVID-19 in this population, protection with an anti-SARS-CoV-2 vaccination is critical. Initial extension to vaccination intervals in the United Kingdom to 12 weeks in December 2020 led to concerns that PCD patients would be left vulnerable for an extended period. Methods A clinical audit was performed on measured serological responses in PCD patients after first and second doses of the BNT162b2 and ChAdOx-1 nCoV-19 vaccines. Antibody levels were measured using Elecsys Anti-SARS-CoV-2S assay (Roche) for quantitative detection of IgG Abs, specific for the SARS-CoV-2 spike-protein. Positive cut-off of 0.80 U/mL defined serological response. Testing was performed at (or closest to) 4 and 8-weeks post-dose. Baseline nucleocapsid Ab results were available from previous screening in a subset of patients. All patients on CIT underwent 4-weekly swabs. Clinical information was retrieved from medical records. Results 188 PCD patients (155 multiple myeloma, 18 amyloid, 10 SMM/MGUS, other 5 PCD), median age 64 (range 32-84), had serological assessment after both vaccine doses. Fourteen with previous COVID-19 infection were excluded. Of 174 patients, 112 were tested after first dose. 88% (153) were on chemo-immunotherapy treatment (CIT). Seropositive rate after first dose was 63% (71/112);of those with available negative baseline antibody test, 62% (31/50) seroconverted. After second dose, 89% (154/174) were seropositive;of those with negative baseline antibody, 90% (61/68) seroconverted. Expectedly, paired median titres after second dose were significantly higher than post first dose (n=112, 3.245 U/mL (IQR 0.4-25.55) vs 518 U/mL (IQR 29.40-2187) p<0.0001) (Figure 1A). Of 41 patients seronegative after first dose, 25 (61%) seroconverted after second, though with lower titres than those only requiring one dose (Figure 1B). Active CIT, disease response less than PR, >=4 lines therapy, light-chain disease, male gender and not responding to first dose were significant factors for not responding to two vaccine doses. We explored <400 U/mL as sub-optimal response (in keeping with upcoming booster study eligibility, OCTAVE-DUO(1), also encompassing the lower quartile of reported healthy controls(2)), which included 43% (75/174) patients. Age 70 years, male gender, >=4 lines of treatment were independent predictors of less-than-optimal response (anti-CD38 CIT of borderline significance). Importantly, vaccine dosing intervals classified as =<42 vs >42 days (Figure 1C) or 28 +/- 14 days vs 84 +/- 14 days (excluding n=66 in neither) (Figure 1D) did not show difference in both definitions of response, neither did vaccine type. Fourteen with previous COVID-19 infection responded to one vaccine dose, median titres 2121 U/mL (IQR 23.48- 2500)) rising to median 2500 U/mL (IQR 2500-2500) after second dose (Figure 1E), significantly higher than those without previous infection. Conclusion Serological response to COVID-19 vaccine is lower in PCD patients than reported healthy controls at 63% after first dose, rising to 89% after second dose, despite extended dosing intervals. PCD patients should be prioritised for shorter intervals, as we show that patients seronegative after first dose, respond after second dose. Further work in PCD is needed to understand how Ab levels correlate to neutralisation capability, cellular responses, protection from infection and how long seroconversion lasts to better define correlates of protection. A booster vaccination or prophylactic passive antibody strategy may be required for those identified at risk, shown not to have responded to two vaccine doses or to have less-than-optimal response. Results from these trials will be eagerly awaited. (Figure Presented).

Risks for Hospitalization and Death Among Patients with Blood Disorders from the ASH RC COVID-19 Registry for Hematology

INTRODUCTION: Patients (pts) with blood disorders are at particular risk for severe infection and death from COVID-19. Factors that contribute to this risk, including cancer treatment, have not been clearly delineated. The ASH RC COVID-19 Registry for Hematology is a public-facing, volunteer registry reporting outcomes of COVID-19 infection in pts with underlying blood disorders. We report a multivariable analysis of the impact of cancer treatment and other key variables on COVID-19 mortality and hospitalization among pts with blood cancer. METHODS: Data were collected between April 1, 2020, and July 2, 2021. All analyses were performed using R version 4.0.2. Multivariable logistic regression explored associations between mortality and seven patient/disease factors previously reported as important to COVID-19 outcome. Independent variables included: age (>60);sex;presence of a major comorbidity (defined as any of heart disease, hypertension, pulmonary disease and/or diabetes);type of hematologic malignancy;estimated prognosis of < 6 months prior to COVID-19;deferral of ICU care;and administration of cancer treatment in the previous year (excluding single agent hydroxyurea). A secondary multivariable logistic regression explored associations between the same variables and hospitalization with COVID-19. RESULTS: We included all pts in the registry with a malignant diagnosis except for 3 patients excluded based on a data sharing agreement (N=1029). Median age category was 50-59y (range <5y to > 90y). The sample was 42% female and 28% had major comorbidities. Types of hematologic malignancies were 354 (34%) acute leukemia/MDS, 255 (25%) lymphoma, 206 (20%) plasma cell dyscrasia (myeloma/amyloid/POEMS), 116 (11%) CLL, 98 (10%) myeloproliferative neoplasm (MPN). Most pts (73%) received cancer treatment during the previous year, 9% had a pre-COVID-19 prognosis of <6months, and 10% deferred ICU care. COVID-19 mortality in the entire cohort was 17%. In multivariable analyses, age > 60 (OR 2.03, 1.31-3.18), male sex (OR 1.69, 1.11 - 2.61), estimated pre-COVID-19 prognosis of less than 6 months (OR 6.16, 3.26 - 11.70) and ICU deferral (OR 10.87, 6.36 - 18.96) were all independently associated with an increased risk of death. Receiving cancer treatment in the year prior to COVID-19 diagnosis and type of hematologic malignancy were not significantly associated with death. In multivariable analyses, age > 60 (OR 2.46, 1.83 - 3.31), male sex (OR 1.34, 1.02 - 1.76), estimated pre-COVID-19 prognosis of < 6 months (OR 4.81, 2.45 - 10.50), presence of a major comorbidity (OR 1.57, 1.15 - 2.16), and cancer treatment in the previous year (OR 1.50, 1.10 - 2.06) were all independently associated with an increased risk of a severe COVID-19 requiring hospitalization. Pts with a MPN or plasma cell dyscrasia and COVID-19 were less likely to require hospitalization for COVID-19 compared to patients with CLL, leukemia/MDS, or lymphoma. CONCLUSIONS: These analyses confirm the negative impact of age > 60, male sex, pre-COVID-19 prognosis of < 6 months, and deferral of ICU care on mortality among patients with hematologic malignancy and COVID-19. We did not observe an increased risk of COVID-19 mortality among pts with COVID-19 who received blood cancer treatment in the previous year, although rate of hospitalization was higher. Pts with some hematologic malignancies (MPN, plasma cell dyscrasias), may experience less severe COVID-19 infections than others. Disclosures: Anderson: Celgene: Membership on an entity's Board of Directors or advisory committees;Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Desai: Janssen R&D: Research Funding;Astex: Research Funding;Kura Oncology: Consultancy;Agios: Consultancy;Bristol Myers Squibb: Consultancy;Takeda: Consultancy. Goldberg: Celularity: Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Aptose: Consultancy, Research Funding;Prelude Therapeutics: Research Funding;DAVA Oncology: Honoraria;Pfizer: Research Funding;Arog: Research Funding;Aprea: Research Funding;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership;Pharmacyclics: Research Funding. Radhakrishnan: Janssen India: Honoraria;Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Aurigene: Speakers Bureau;Novartis: Honoraria;Johnson and Johnson: Honoraria;Pfizer: Consultancy, Honoraria;Astrazeneca: Consultancy, Honoraria;Emcure Pharmaceuticals: Other: payment to institute;Cipla Pharmaceuticals: Honoraria, Other: payment to institute;Bristol Myers Squibb: Other: payment to institute;Roche: Honoraria, Other: payment to institute;Intas Pharmaceutical: Other: payment to institute;NATCO Pharmaceuticals: Research Funding. Sehn: Genmab: Consultancy;Debiopharm: Consultancy;Novartis: Consultancy. Sekeres: Novartis: Membership on an entity's Board of Directors or advisory committees;Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees. Tallman: Kura: Membership on an entity's Board of Directors or advisory committees;Syros: Membership on an entity's Board of Directors or advisory committees;Innate Pharma: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Biosight: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Jazz Pharma: Membership on an entity's Board of Directors or advisory committees;Oncolyze: Membership on an entity's Board of Directors or advisory committees;KAHR: Membership on an entity's Board of Directors or advisory committees;Orsenix: Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Amgen: Research Funding;Rafael Pharmaceuticals: Research Funding;Glycomimetics: Research Funding;Biosight: Research Funding;Orsenix: Research Funding;Abbvie: Research Funding;NYU Grand Rounds: Honoraria;Mayo Clinic: Honoraria;UC DAVIS: Honoraria;Northwell Grand Rounds: Honoraria;NYU Grand Rounds: Honoraria;Danbury Hospital Tumor Board: Honoraria;Acute Leukemia Forum: Honoraria;Miami Leukemia Symposium: Honoraria;New Orleans Cancer Symposium: Honoraria;ASH: Honoraria;NCCN: Honoraria.

Bortezomib As Frontline Therapy in the Management of TTP

Introduction The current International Society on Thrombosis and Hemostasis (ISTH) guideline of Thrombotic Thrombocytopenic Purpura (TTP) recommends Therapeutic Plasma exchange (TPE) and corticosteroid in the management of TTP, with Rituximab and Caplasizumab as additional potential therapies [X Long Zheng et al, J Thromb Haemost. 2020;18:2496-2502]. This potentially fatal condition requires prompt diagnosis and treatment but large volume plasma treatment is not without risk and in settings with limited access with sufficient compatible plasma for apheretic exchange, this can delay this emergency therapy. We have been running the first therapeutic apheresis services with an Optia instrument in Uganda at the Joint Clinical Research Centre in Kampala city and TTP is the main indication for TPE. We present 2 recent sequential cases of TTP that were successfully managed when Bortezomib was combined with plasma therapy. Case1. A 25yr woman referred to our service on 29/09/2020, with recent onset of bruising, icterus, severe anemia Hgb5.7g/dL, Severe thrombocytopenia 8 x 10 3/uL, a high LDH 3909U with schistocytes on the peripheral blood film severe thrombocytopenia and a negative Direct Antiglobulin test. She was Blood Group B+. She was managed with 3 sessions of TPE of 2.1, 1.1 and 2.0 plasma volume exchanges with 6727mL, 3026mL and 5459mL of replacement plasma respectively and oral prednisone 60mg daily without remission. Subsequent quantities of plasma were insufficient for apheresis and were instead transfused. She also received weekly Rituximab 500mg (IV) but without significant recovery in the platelet count until she received Bortezomib 2mg (SC) when there was corresponding recovery of the platelet count and with each dose to a total of 4 doses (Figure 1). Case2. A 55yr man was previously well and shopping in a mall when he had an index episode of seizures on 19.Jun.2021 and was hospitalized that day with altered consciousness and focal motor signs. He required intubation for 3 days and at the time of hospitalization, he had Hgb 9gm/dL, PLT 17 x 10 3/uL, LDH2177U, with numerous schistocytes on the peripheral blood film and a negative Direct Antiglobulin Test. The baseline blood sample functional ADAMTS13 was 3% and had Blood Group AB+. He had received the 1 st dose of the Astra-Zeneca Covid19 vaccine on 06.May.2021. It was not possible to get any AB plasma and we considered it risky to perform large volume TPE with non-AB plasma and he was instead treated with daily transfusion with Group A+ Plasma concurrent with daily Prednisone 60mg. Because of our previous experience of poor response to Rituximab, we opted to treat him upfront with 4 doses of 2mg bortezomib (SC) given 3 days apart. He made brisk recovery to complete remission and was discharged for weekly outpatient CBC and LDH monitoring. His platelet count subsequently dropped without a corresponding drop in the Hgb and no rise in the Hgb. We initially re-hospitalized him for 4 more days of plasma transfusion but without a brisk response and since the LDH was not increasing, the isolated Thrombocytopenia was considered a side effect of Bortezomib that was expected to resolve and he receive no further treatment but continued to recover to complete remission as an out-patient (figure 2). Discussion: Our findings suggest a possible role for Bortezomib in frontline therapy for TTP with potential to reduce the plasma requirement in TPE and this approach warrants a randomized clinical trial. [Formula presented] Disclosures: No relevant conflicts of interest to declare. OffLabel Disclosure: Bortezomib Indicated in the management of Multiple Myeloma and Plasma Cell Dyscrasia

COVID-19 Vaccine Response in Patients with Hematologic Malignancy: A Systematic Review and Meta-Analysis

Introduction: Emerging data suggests that seroresponse (SR) in patients with hematologic malignancy following COVID-19 vaccination is likely lower than in patients without blood cancer. The objective of this study was to perform a systematic review and meta-analysis on SR in patients with hematologic malignancy who received COVID-19 vaccination (submitted to PROSPERO for registration). Methods: We searched PubMed and EMBASE from December 1, 2020, to July 22, 2021, to identify studies of SR following COVID-19 vaccine in adult patients with hematologic malignancy (including studies in which patients with hematologic malignancy represented a subset of a broader population). Patients with positive serologic response at baseline (prior to vaccination) or known COVID-19 infection were excluded. The primary outcomes were pooled SR estimates following COVID-19 vaccination in patients with hematologic malignancy, and pooled SR estimates of subgroups based on hematologic malignancy type. Secondary outcomes were pooled relative risk ratio (RR;compared to non-cancer controls) based on dichotomous-effect SR in all patients, and subgroups based on hematologic malignancy type, treatment status, and use of anti-CD20 therapy. Pooled estimates and RR with its associated 95% confidence intervals (CIs) were calculated using MetaXL (EpiGear), and Reference Manager (Cochrane) using random effects model. Results A total of 17 studies comprising 2834 patients with hematologic malignancy from Europe, United Kingdom and North America were included (Figure 1). The pooled estimate for SR was 58% (95% CI 48-67%, I 2 95%), with a RR of 0.53 (95% 0.42-0.66, I 2 94%) when compared to controls (10 studies with comparison group, 1092 hematologic malignancy patients, 830 controls;Figure 2). The pooled estimate for SR varied by type of hematologic malignancy: lymphomas SR 52% (95% CI 36-68%, 7 studies, 832 patients, I 2 94%);chronic lymphocytic leukemia (CLL) SR 42% (95% CI 25-60%, 6 studies, 921 patients, I 2 93%);plasma cell dyscrasias SR 66% (95% CI 47-83%, 8 studies, 611 patients, I 2 95%);myeloproliferative neoplasms (MPNs, including chronic myelogenous leukemia) SR 83% (95% CI 68-95%, 6 studies, 227 patients, I 2 58%);acute leukemia SR 86% (95% CI 77-94%, 2 studies, 67 patients, 46 acute myelogenous leukemia [AML] and 15 acute lymphocytic leukemia], I 2 0%). The RR for SR also varied by type of hematologic malignancy: lymphomas (excluding CLL) RR 0.48 (95% CI 0.34-0.68, 4 studies, 337 patients, I 2 89%);CLL RR 0.37 (95% CI 0.25-0.53, 3 studies, 194 patients, I 2 54%);plasma cell dyscrasias RR 0.73 (95% CI 0.62-0.86, 5 studies, 323 patients, I 2 70%);RR MPN 0.78 (95% CI 0.62-0.99, 3 studies, 199 patients, I 2 90%). The pooled estimate for SR in those receiving treatment was 42% (95% CI 26-58%, 9 studies, 683 patients, I 2 94%). The pooled estimates for SR for those receiving anti-CD20, bruton tyrosine kinase inhibitor (BTKi), or venetoclax were 13% (95% CI 1-32%, 6 studies, 367 patients, I 2 88%), 42% (95% CI 17-71%, 3 studies, 319 patients, I 2 75%), and 20% (95% CI 0-54%, 3 studies, 39 patients, I 2 66%), respectively. The RR for those receiving treatment for their hematologic malignancy compared to those who were not receiving treatment was 0.51 (95% CI 0.37-0.71, 8 studies, 579 patients, I 2 89%;Figure 3). The RR of patients receiving anti-CD20 therapy compared to non-cancer controls was 0.13 (95% CI 0.02-0.93, 102 patients, I 2 73%). For patients treated with anti-CD20 therapy, the RR of those receiving vaccination within 9-12 months compared to beyond 9-12 months was 0.12 (95% CI 0.06-0.25, 2 studies, 74 patients, I 2 0%;Figure 4). Conclusion: Our systematic review and meta-analysis suggests that patients with hematologic malignancy have a lower SR rate following vaccination compared to controls. Furthermore, SR is variable across different types of hematologic malignancy, with very good response rates seen in patients with myeloid diseases (MPN and AML) and poor response rates seen in lymphoma and CLL. Active treatment, particu arly anti-CD20 therapy within 12 months of vaccination, is associated with a particularly low SR following vaccination. Additional studies are needed to understand non-humoral responses to vaccination, and to guide decisions regarding how to optimize vaccine response in patients with blood cancer. We plan to update the systematic review and meta-analysis as more data become available. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Severity of Covid-19 Clinical Outcomes and Mortality in Multiple Myeloma Patients over Year 1 of the Pandemic

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.

COVID Infection and Hematological Malignancy-Double Whammy

Introduction: The covid-19 pandemic had resulted in all thehealthcare infrastructure being diverted to the management of thepandemic. This has resulted in other diseases being side-lined. Thelong term consequence of this is yet to be known. In our study, weaimed to study how the diagnosis of covid changed the managementin hematological malignancies. We hope that the lessons learnt from this will help us manage the treatment of hematological malignanciesin a better way.Aims &Objectives: In this study, we aimed to report the clinicalprofile and outcomes of COVID-19 in patients with haematologicalmalignancy at a tertiary care hospital.Materials &Methods: It is an observational study. Data from laboratory-confirmed 40 COVID-19 patients diagnosed between 1January 2021 and 31 July 2021 were analysed retrospectively. AllCOVID-19 patients with haematological malignancy (n = 40) wereincluded in the study.Result: In this present study, total 40 patients were included. Of these,25(62.5%) were males and 15(37. 5%) were females. The median agein this study was 43 years. (Range, 8-70). Of these 40 patients, acutemyeloid Leukemia was the commonest malignancy (27.5%), followedby acute lymphoblastic Leukemia (22.5%) then non-Hodgkin lymphoma (12.5%), plasma cell dyscrasia (10%), chronic myeloid Leukemia (10%), chronic lymphocytic Leukemia (7.5%), acutepromyelocytic Leukemia (5%), chronic myelomonocytic Leukemia(5%). Mean hemoglobin was (8.04 gm/dl), WBC count was(10.14 × 109/l), platelet count was (77.7 × 109/l) creatinine was(0.86 mg/dl), bilirubin was (1.24 mg/dl). The median delay in initiating chemotherapy was 17 days. The average stay in the covid wardwas 12.8 days. Over all Case fatality rate was 22.5%. The meannumber of days for rt-pcr to turn negative was 11.2 days, with onepatient with severe covid remaining positive for 27 days. Thrombosiswas not seen in any of our patients even though malignancy and covidare both associated with increased thrombotic risk.Conclusions: Patients with haematological malignancy areimmunocompromised, and our study reveals that there is an increasedcase fatality rate among these patients. The delay in initiatingchemotherapy-both because of covid illness and also because oflimitation with initiating chemotherapy in the covid ward resulted in ahigher case mortality. Therefore, physicians should pay great attention to the management of COVID-19 patients with haematologicalmalignancy.

30-Day Mortality Following Systemic Anti-Cancer Treatment (SACT) Review in Driving Quality of Care in Hematologic Malignancies in a Tertiary Care Hospital

Introduction There is growing evidence to support SACT 30-day mortality rate as a key metric for assessing quality of cancer care and a key indicator of avoidable harm to patients from SACT due therapy-related or poor patient selection factors. This has been established for solid organ malignancy. However, data in patients with hematologic malignancy is limited. At the Gloucestershire Hospitals NHS Foundation Trust, a large district general hospital providing specialist care to over 600,000 people, we collated data from our in-house SACT dataset to assess factors that impact the 30-day SACT mortality and establish a benchmark for multidisciplinary, educational mortality meeting discussions on mortality in patients receiving SACT. We aimed to review cases characterizing patients, causes of death and the role of SACT in deaths. Methods This retrospective study included all patients aged 18 years or older with a hematologic malignancy who received SACT between Jan 1, 2016, and Mar 31, 2021, irrespective of the number of previous treatment cycles or regimens and irrespective of their response within the disease trajectory. SACT was defined as any cytotoxic chemotherapy, immunotherapies such as monoclonal antibodies, and targeted biological treatments. We calculated 30-day mortality after the most recent cycle of SACT for these patients. We analyzed whether patient, tumor type, and therapy-related factors were associated with the risk of 30-day mortality. Results A total of 1903 patients with hematologic malignancy received SACT. The 30-day mortality rate for our center was 3.89% for patients receiving SACT and 4.9% of all-cause mortality. In the 30-day mortality cohort the median patient age at death was 71 years (interquartile range (IQR) 52-86);ratio of men to women, 1.18. 30-day mortality increased with age for patients treated with palliative intent or intent to remission (OR 4.9, 95% CI.985-26.255;p=0.0171). Median duration of 30-mortality post SACT was 17 days (IQR 8-22). The commonest malignancy was plasma cell dyscrasias (54%) and 68% receiving treatments with intent to remission. ECOG performance status was 0-2 at final SACT cycle in 65%, 3 in 27% and 4 in 8%. 47% of patients were receiving their first cycle (median number of cycles received 2;IQR 1-3) and 43% receiving first line therapy (median lines of therapy 2;IQR 1-3). Therapy naïve patients had significantly higher 30-day mortality than those who received previous SACT (OR 3.435, 95% CI 2.06-5.66;p<0·0001). 42% of deaths occurred in hospital and 54% were attributed to primary refractory and/or aggressive disease. Other causes of death included infection (19% neutropenic, 15% non-neutropenic) including COVID-19 (3%), major bleed (5%), thromboembolism (1%) and cardiac event (1%). Conclusions SACT data provides “real world” assessment of treatment patterns and outcomes in routine malignant hematology practice. It highlights the importance of systematic data collection and analyses to better inform factors associated with higher risk of 30-day mortality in patients with hematologic malignancy, which ultimately promotes review of clinical decision making and offers an opportunity for service improvements. Our findings shed light into some of the factors that affect the risk of early mortality of patients with hematologic malignancy and provides a way to measure if the health service is improving. The insights into risk factors for 30-day mortality will aid in better understanding for treating clinicians and their patients on predictors of potential harms and benefits of SACT thereby carefully balancing patients' personalized expectations with representative outcomes and treatment risks and should be the focus of discussions about SACT, particularly in pretreated or older patient groups. Neutropenic sepsis remains a significant cause of SACT related mortality warranting further improvements in care. Prospective case discussions together with this retrospective review have generated service improvements at our center including standardizing chemothe apy helpline pathways, systematizing SACT mandatory data recording on e-prescribing system and mandatory response assessments as part of SACT protocols' review. Future research work to examine outcomes based on subtypes of hematologic malignancy and on larger datasets is critical for improving our understanding at delivering the right drugs to the right patients. Disclosures: No relevant conflicts of interest to declare.