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1.
Clin Lab ; 67(11)2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1818667

ABSTRACT

BACKGROUND: Immunoglobulin D multiple myeloma (IgD-MM) is a rare but aggressive disease. The safety and effectiveness of anti-CD38 monoclonal antibody (daratumumab) have not been known in either IgD-MM or MM complicated with secondary neoplasm. METHODS: A fragile IgD-MM patient had an aggressively relapsed disease concurrent with lung cancer and severe thrombocytopenia, which led to a dilemma for management. After a failure of ixazomib-based chemotherapy, a salvage therapy with daratumumab unexpectedly induced complete remission and platelet recovery, and the patient successfully proceeded to lung cancer surgery. CONCLUSIONS: Our case indicates daratumumab is both safe and effective for refractory IgD-MM with severe complications.


Subject(s)
Lung Neoplasms , Multiple Myeloma , Thrombocytopenia , Antibodies, Monoclonal , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Humans , Immunoglobulin D , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy
2.
Crit Rev Oncol Hematol ; 172: 103623, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1748099

ABSTRACT

Daratumumab is approved for newly diagnosed or relapsed/refractory multiple myeloma (MM). The use of daratumumab has improved patient outcomes but has changed the frequency and epidemiology of infections. However, the optimal approach to prophylaxis and supportive therapy for daratumumab-emergent infections is unknown and represents an unmet clinical need in MM. Consequently, an expert panel convened to compose recommendations for optimal infection control in patient candidates to or under daratumumab treatment for MM. Scientific evidence on infections secondary to daratumumab was evaluated, and a consensus was developed by group discussion for key questions selected according to the clinical relevance. The following key issues were addressed: infectious risk assessment and risk stratification, infection mitigation strategies, and management of infectious complications in patients with MM treated with daratumumab.


Subject(s)
Multiple Myeloma , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Consensus , Humans , Multiple Myeloma/complications , Multiple Myeloma/drug therapy
5.
Emerg Infect Dis ; 27(11): 2973-2975, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1551460

ABSTRACT

A young man with smoldering multiple myeloma died of hypotensive shock 2.5 days after severe acute respiratory syndrome coronavirus 2 vaccination. Clinical findings suggested systemic capillary leak syndrome (SCLS); the patient had experienced a previous suspected flare episode. History of SCLS may indicate higher risk for SCLS after receiving this vaccine.


Subject(s)
COVID-19 , Capillary Leak Syndrome , Multiple Myeloma , SARS Virus , Capillary Leak Syndrome/chemically induced , Capillary Leak Syndrome/diagnosis , Humans , Male , Multiple Myeloma/complications , SARS-CoV-2
6.
Br J Haematol ; 196(4): 892-901, 2022 02.
Article in English | MEDLINE | ID: covidwho-1511287

ABSTRACT

Patients with haematological malignancies have a high risk of severe infection and death from SARS-CoV-2. In this prospective observational study, we investigated the impact of cancer type, disease activity, and treatment in 877 unvaccinated UK patients with SARS-CoV-2 infection and active haematological cancer. The primary end-point was all-cause mortality. In a multivariate analysis adjusted for age, sex and comorbidities, the highest mortality was in patients with acute leukaemia [odds ratio (OR) = 1·73, 95% confidence interval (CI) 1·1-2·72, P = 0·017] and myeloma (OR 1·3, 95% CI 0·96-1·76, P = 0·08). Having uncontrolled cancer (newly diagnosed awaiting treatment as well as relapsed or progressive disease) was associated with increased mortality risk (OR = 2·45, 95% CI 1·09-5·5, P = 0·03), as was receiving second or beyond line of treatment (OR = 1·7, 95% CI 1·08-2·67, P = 0·023). We found no association between recent cytotoxic chemotherapy or anti-CD19/anti-CD20 treatment and increased risk of death within the limitations of the cohort size. Therefore, disease control is an important factor predicting mortality in the context of SARS-CoV-2 infection alongside the possible risks of therapies such as cytotoxic treatment or anti-CD19/anti-CD20 treatments.


Subject(s)
Antigens, CD20/immunology , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/complications , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Adult , Antineoplastic Agents, Immunological/adverse effects , COVID-19/etiology , COVID-19/immunology , Female , Hematologic Neoplasms/immunology , Humans , Leukemia/complications , Leukemia/drug therapy , Leukemia/immunology , Male , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , Prospective Studies , Risk Factors
7.
Lancet Haematol ; 8(12): e934-e946, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1486371

ABSTRACT

Patients with multiple myeloma frequently present with substantial immune impairment and an increased risk for infections and infection-related mortality. The risk for infection with SARS-CoV-2 virus and resulting mortality is also increased, emphasising the importance of protecting patients by vaccination. Available data in patients with multiple myeloma suggest a suboptimal anti-SARS-CoV-2 immune response, meaning a proportion of patients are unprotected. Factors associated with poor response are uncontrolled disease, immunosuppression, concomitant therapy, more lines of therapy, and CD38 antibody-directed and B-cell maturation antigen-directed therapy. These facts suggest that monitoring the immune response to vaccination in patients with multiple myeloma might provide guidance for clinical management, such as administration of additional doses of the same or another vaccine, or even temporary treatment discontinuation, if possible. In those who do not exhibit a good response, prophylactic treatment with neutralising monoclonal antibody cocktails might be considered. In patients deficient of a SARS-CoV-2 immune response, adherence to measures for infection risk reduction is particularly recommended. This consensus was generated by members of the European Multiple Myeloma Network and some external experts. The panel members convened in virtual meetings and conducted an extensive literature research and evaluated recently published data and work presented at meetings, as well as findings from their own studies. The outcome of the discussions on establishing consensus recommendations for COVID-19 vaccination in patients with multiple myeloma was condensed into this Review.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Multiple Myeloma/complications , Practice Guidelines as Topic/standards , Consensus , Humans , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , SARS-CoV-2 , Vaccination
9.
Br J Haematol ; 196(2): 356-359, 2022 01.
Article in English | MEDLINE | ID: covidwho-1412420

ABSTRACT

Patients with multiple myeloma (MM) have a suboptimal antibody response following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and lower seroconversion rates following coronavirus disease 2019 (COVID-19) compared with healthy individuals. In this context, we evaluated the development of neutralising antibodies (NAbs) against SARS-CoV-2 in non-vaccinated patients with MM and COVID-19 compared with patients after vaccination with two doses of the BNT162b2 vaccine. Serum was collected either four weeks post confirmed diagnosis or four weeks post a second dose of BNT162b2. NAbs were measured with a Food and Drug Administration-approved enzyme-linked immunosorbent assay methodology. Thirty-five patients with COVID-19 and MM along with 35 matched patients were included. The two groups did not differ in age, sex, body mass index, prior lines of therapy, disease status, lymphocyte count, immunoglobulin levels and comorbidities. Patients with MM and COVID-19 showed a superior humoral response compared with vaccinated patients with MM. The median (interquartile range) NAb titre was 87·6% (71·6-94%) and 58·7% (21·4-91·8%) for COVID-19-positive and vaccinated patients, respectively (P = 0·01).Importantly, there was no difference in NAb production between COVID-19-positive and vaccinated patients who did not receive any treatment (median NAb 85·1% vs 91·7%, P = 0·14). In conclusion, our data indicate that vaccinated patients with MM on treatment without prior COVID-19 should be considered for booster vaccine doses.


Subject(s)
Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , COVID-19/immunology , Multiple Myeloma/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/complications , COVID-19/prevention & control , COVID-19 Serological Testing , Epitopes/immunology , Female , Humans , Immunization, Secondary , Immunocompromised Host , Immunogenicity, Vaccine , Male , Middle Aged , Multiple Myeloma/complications , Prospective Studies , Vaccination
13.
Emerg Infect Dis ; 27(11): 2973-2975, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1378184

ABSTRACT

A young man with smoldering multiple myeloma died of hypotensive shock 2.5 days after severe acute respiratory syndrome coronavirus 2 vaccination. Clinical findings suggested systemic capillary leak syndrome (SCLS); the patient had experienced a previous suspected flare episode. History of SCLS may indicate higher risk for SCLS after receiving this vaccine.


Subject(s)
COVID-19 , Capillary Leak Syndrome , Multiple Myeloma , SARS Virus , Capillary Leak Syndrome/chemically induced , Capillary Leak Syndrome/diagnosis , Humans , Male , Multiple Myeloma/complications , SARS-CoV-2
15.
Leukemia ; 35(12): 3534-3541, 2021 12.
Article in English | MEDLINE | ID: covidwho-1333898

ABSTRACT

Multiple myeloma (MM) patients are at higher risk for severe COVID-19. Their mRNA vaccination response against SARS-CoV-2 is unknown. Thus, we analyzed responses to mRNA vaccination against COVID-19 among these patients. Using an ELISA-based assay that detects IgG antibodies to SARS-CoV-2 spike protein, we determined serum antibody levels prior to immunization and 12-21 and 14-21 days following the first and second vaccinations, respectively, with mRNA-1273 (Moderna) or BNT162b2 (Pfizer/BioNTech) among 103 MM patients (96 and 7 with active and smoldering disease, respectively). We stratified patients into clinically relevant responders (>250 IU/mL), partial responders (50-250 IU/mL, which was above pre-COVID-19 background), and nonresponders (<50 IU/mL). Smoldering MM patients responded better than those with active disease. Only 45% of active MM patients developed an adequate response, while 22% had a partial response. Lower spike antibody levels were associated with older age, impaired renal function, low lymphocyte counts, reduced uninvolved immunoglobulin levels, > second line of treatment, and among those not in complete remission. Patients who received mRNA-1273 vaccine had higher anti-spike antibody levels than those who were vaccinated with BNT162b2. Thus, most MM patients have impaired responses to mRNA vaccination against COVID-19, and specific clinical and myeloma-related characteristics predict vaccine responsiveness.


Subject(s)
/administration & dosage , Antibodies, Viral/blood , COVID-19/therapy , Multiple Myeloma/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , /immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/epidemiology , COVID-19/virology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/virology , Vaccination
17.
Ann Hematol ; 100(10): 2541-2546, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1323925

ABSTRACT

Infections are the primary cause of morbidity and mortality in multiple myeloma (MM) patients (pts). The aim of our retrospective analysis was to evaluate incidence and course of COVID-19 infection in a cohort of 351 MM outpatients treated with novel drugs. COVID-19 disease was detected in 50/351 pts (14%); median age was 68 years. Gender, ISS stage, and last treatment lines were as follows: male 32, female 18; ISS-I 19, ISS-II 20, ISS-III 11; daratumumab-based 15, lenalidomide-based 12, bortezomib-based 17, other 6. Positive PCR test at COVID-19 diagnosis was present in all pts; anti-myeloma treatment was interrupted. Hospitalizations for COVID-19 pneumonia were necessary for 28/50 pts (56%), 18/50 pts (36%) in standard unit (SU) 10/50 pts (20%) in intensive care unit (ICU), and 9/50 pts (18%) died. The statistically significant parameters for COVID-19 hospitalization were as follows: responsive versus non-responsive disease (p = 0.027), ECOG performance status 0-2 versus ≥ 3 (p = 0.014), presence of comorbidities (0-1 versus ≥ 2, p = 0.043). The statistically significant factors for COVID-19 death were as follows: ECOG 0-2 versus ≥ 3 (p = 0.001), presence of comorbidities (0-1 versus ≥ 2, p = 0.007), serious course of COVID-19 disease with ICU hospitalization (SU versus ICU, p = 0.001). None of the other studied risk factors was associated with poor outcome (age, gender, ISS stage, immunoparesis, type of anti-myeloma treatment). Full recovery from COVID-19 infection was observed in 41/50 pts (82%) in median of 32 days. The course of COVID-19 disease in MM pts was mostly moderate or serious with 56% of hospitalizations and 18% of deaths.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Bortezomib/therapeutic use , COVID-19/etiology , Lenalidomide/therapeutic use , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/diagnosis , Female , Hospitalization , Humans , Incidence , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification , Treatment Outcome
18.
Br J Haematol ; 195(2): 186-193, 2021 10.
Article in English | MEDLINE | ID: covidwho-1289897

ABSTRACT

Multiple myeloma (MM) patients are at excess risk for clinically significant COVID19 infection. BNT162b2 mRNA COVID19 (BNT162b2) vaccine provides effective protection against COVID19 for the general population, yet its effect in MM patients may be compromised due to disease and therapy-related factors and was not yet evaluated. This single-centre prospective study included MM patients tested for serological response 14-21 days post second vaccine. Vaccinated healthy volunteers served as controls. In all, 171 MM patients, median age 70 (38-94) were included; 159 active MM and 12 smouldering myeloma (SMM). Seropositive response rate (median titer) was 76% (91 U/ml) in active MM patients vs 98% (992 U/ml) in the 64 controls (P < 0·0001), and 100% (822 U/ml) in SMM patients. Multivariate analysis revealed older age (P = 0·009), exposure to ≥4 novel anti-myeloma drugs (P = 0·02) and hypogammaglobulinaemia (P = 0·002) were associated with lower response rates. None of the novel agents significantly decreased response rate, whereas daratumumab trended towards reduced response (P = 0·08). Adverse events occurred in 53% and 55% of the MM patients and controls, respectively, all transient grade 1-2. In conclusion, BNT162b2 vaccine was safe and provided a high seropositivity rate in MM patients, independent of treatment type. Older, hypogammaglobulinaemic and heavily pretreated patients had lower response rates.


Subject(s)
/adverse effects , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Immunity, Humoral/immunology , Multiple Myeloma/immunology , Adult , Agammaglobulinemia/complications , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , /immunology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Case-Control Studies , Female , Humans , Immunity, Humoral/drug effects , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/diagnosis , Multivariate Analysis , Predictive Value of Tests , Prospective Studies , Risk Factors , SARS-CoV-2/genetics , Treatment Outcome
20.
BMJ Case Rep ; 14(5)2021 May 20.
Article in English | MEDLINE | ID: covidwho-1238493

ABSTRACT

We present a 47-year-old, South-African origin, woman with a background of stable monoclonal gammopathy of unknown significance (MGUS) who attended A&E with a history of coryzal symptoms associated with persistent fever, lymphadenopathy and a new onset of rash, not responding to antibiotics and paracetamol. A trial of high-dose steroids resolved symptoms. Bone marrow biopsy confirmed a progression of MGUS into multiple myeloma and her axillary lymph node biopsy analysis supported a diagnosis of Kikuchi-Fujimoto disease (KFD). This is an unusual presentation where KFD has been noted alongside MGUS progression to multiple myeloma. Haematology follow-up is underway.


Subject(s)
Histiocytic Necrotizing Lymphadenitis , Lymphadenopathy , Monoclonal Gammopathy of Undetermined Significance , Multiple Myeloma , Biopsy , Female , Histiocytic Necrotizing Lymphadenitis/complications , Histiocytic Necrotizing Lymphadenitis/diagnosis , Histiocytic Necrotizing Lymphadenitis/drug therapy , Humans , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/diagnosis , Multiple Myeloma/drug therapy
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