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1.
The New England Journal of Medicine ; 387(24):2210, 2022.
Article in English | ProQuest Central | ID: covidwho-2160409
2.
Clinical Infection in Practice ; : 100214, 2022.
Article in English | ScienceDirect | ID: covidwho-2158604

ABSTRACT

We have reported that IgG antibody responses following two mRNA COVID-19 vaccinations are impaired among patients with multiple myeloma (MM). In the current study, sixty-seven patients with MM were tested for anti-spike IgG antibodies 0-60 days prior to their first vaccination, 14-28 days following the second dose, and both before and 14-28 days after their third dose of the mRNA-1273 or BNT162b2 vaccines. After the first two doses, most patients' (93%) antibody levels declined to ineffective levels (<250 BAU/mL) prior to their third dose (D3). D3 elicited responses in 84% of patients (61% full response and 22% partial response). The third vaccination increased antibody levels (average = 370.4 BAU/mL;range, 1.0-8977.3 BAU/mL) relative to just prior to D3 (average = 25.0 BAU/mL;range, 1.0-683.8 BAU/mL) and achieved higher levels than peak levels after the first two doses (average = 144.8 BAU/mL;range, 1.0-4,284.1 BAU/mL). D3 response positively correlated with mRNA-1273, a >10-fold change from baseline for the two-dose series, switching from BNT162b2 to mRNA-1273 for D3, and treatment with elotuzumab and an immunomodulatory agent. Lower antibody levels prior to D3, poorer overall response to first two doses, and ruxolitinib or anti-CD38 monoclonal antibody treatment negatively correlated with D3 response. Our results show encouraging activity of the third vaccine, even among patients who failed to respond to the first two vaccinations. The finding of specific factors that predict COVID-19 antibody levels will help advise patients and healthcare professionals on the likelihood of responses to further vaccinations.

3.
Immun Inflamm Dis ; 10(12): e701, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2127747

ABSTRACT

BACKGROUND: Covid-19 is considered a primary respiratory disease-causing viral pneumonia and, in severe cases, leads to acute lung injury and acute respiratory distress syndrome (ARDS). In addition, though, extra-pulmonary manifestations of Covid-19 have been shown. Furthermore, severe acute respiratory distress syndrome coronavirus type 2 (SARS-CoV-2) infection may coexist with several malignancies, including multiple myeloma (MM). METHODS: This critical literature review aimed to find the potential association between SARS-CoV-2 infection and MM in Covid-19 patients with underlying MM. Narrative literature and databases search revealed that ARDS is developed in both MM and Covid-19 due to hypercalcemia and proteasome dysfunction. RESULTS: Notably, the expression of angiogenic factors and glutamine deficiency could link Covid-19 severity and MM in the pathogenesis of cardiovascular complications. MM and Covid-19 share thrombosis as a typical complication; unlike thrombosis in Covid-19, which reflects disease severity, thrombosis does not reflect disease severity in MM. In both conditions, thromboprophylaxis is essential to prevent pulmonary thrombosis and other thromboembolic disorders. Moreover, Covid-19 may exacerbate the development of acute kidney injury and neurological complications in MM patients. CONCLUSION: These findings highlighted that MM patients might be a risk group for Covid-19 severity due to underlying immunosuppression and most of those patients need specific management in the Covid-19 era.


Subject(s)
COVID-19 , Multiple Myeloma , Respiratory Distress Syndrome , Venous Thromboembolism , Humans , COVID-19/complications , SARS-CoV-2 , Multiple Myeloma/complications , Anticoagulants
4.
Blood Advances ; 2022.
Article in English | ScienceDirect | ID: covidwho-2070704

ABSTRACT

Patients with multiple myeloma (MM) have diminished immune response to COVID-19 vaccines. Risk factors for an impaired immune response are yet to be determined. We aimed to summarize the COVID-19 vaccine immunogenicity, and to identify factors that influence the humoral immune response in patients with MM. Two reviewers independently conducted a literature search in MEDLINE, Embase, ISI Web of Science, Cochrane library, and Clinicaltrials.gov from existence through May 24th, 2022. (PROSPERO: CRD42021277005). Fifteen and five studies were included in the systematic review and meta-analysis, respectively. The average rate (range) of positive functional T-lymphocyte response was 44.2% (34.2% - 48.5%) after 2 doses of mRNA COVID-19 vaccines. The average anti-spike antibody response rates (range) were 42.7% (20.8% - 88.5%) and 78.2% (55.8% - 94.2%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. The average neutralizing antibody response rates (range) were 25% (1 study) and 62.7% (53.3% - 68.6%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. Patients with high-risk cytogenetics or receiving anti-CD38 therapy were less likely to have a humoral immune response with pORs of 0.36 (0.18, 0.69), I2=0% and 0.42 (0.22, 0.79), I2=14%, respectively. Patients who were not on active MM treatment were more likely to respond with pOR of 2.42 (1.10, 5.33), I2=7%. Patients with MM had low rates of humoral and cellular immune response to the mRNA COVID-19 vaccines. Further studies are needed to determine the optimal doses of vaccines and evaluate the utilization of monoclonal antibodies for pre-exposure prophylaxis in this population.

5.
Intensiv- und Notfallbehandlung ; 47(3):156-161, 2022.
Article in German | EMBASE | ID: covidwho-2067042

ABSTRACT

Background: Lung ultrasound is an im-portant tool for distinguishing between causes and therapies of cardiorespiratory diseases in emergency departments (ED). Aim and method: Based on a case report, the importance of point-of-care ultrasound (POCUS) in the context of emergency di-agnostics and intensive care therapy will be illustrated. Case report: A 78-year-old male presented to the ED with dyspnea und weakness. A double mRNA-Covid vaccination was completed 3 months before. His medical history revealed multiple myeloma. Using POCUS, a severe Covid-19 pneumonia could be suspected, and at the same time other differential diagnoses were ruled out. PCR confirmed a SARS-CoV-2 infection. The patient was admitted to our intensive care unit with severe Covid-19 pneumonia fol-lowed by a complicated and ultimately le-thal course. Conclusion(s): In immunocompro-mised patients, there is still a high risk of a severe and complex course despite vaccina-tion. POCUS allows evaluation of probable Covid-19 pneumonia and rapid exclusion of possible differential diagnoses. Copyright © 2022 Dustri-Verlag Dr. K. Feistle.

6.
J Clin Med ; 11(19)2022 Oct 07.
Article in English | MEDLINE | ID: covidwho-2066201

ABSTRACT

Lenalidomide-based regimens are effective treatment options for patients with relapsed/refractory multiple myeloma (RRMM). However, they are associated with an increased risk of infectious complications. This study examines the clinical factors influencing the occurrence of infection in MM patients treated with lenalidomide and dexamethasone (Rd). A retrospective analysis of all patients who received the Rd regimen between 2017 and 2021 at our institution was performed. The study group consisted of 174 patients and the median age was 65 years. Most patients (n = 110, 63.2%) received the Rd treatment in second-line treatment. The majority of patients (64.3%) received bortezomib-based regimens in the first line of treatment. The median progression-free survival was 12.6 (95% CI: 9.5-16.2) months, and the median overall survival was 22.3 (95% CI: 15.9-28.6) months. The overall response rate was 64.1%, 12.7% of patients achieved complete response, and 20.4% had a very good partial response. In multivariate logistic regression analysis, hypoalbuminemia (OR 4.2, 95% CI: 1.6-11.2, p = 0.0039), autologous hematopoietic stem cell transplantation (AHSCT) before Rd (OR 2.6, 95% CI: 1.0-6.7, p = 0.048), and anemia grade ≥3 (OR 5.0, 95% CI: 1.8-14.0, p = 0.002) were independent factors related to the occurrence of infections. In conclusion, in this large cohort of RRMM patients, AHSCT before Rd regimen therapy, hypoalbuminemia, and anemia during treatment were identified as three independent factors influencing the frequency of infections during Rd therapy. Patients with established risk factors may benefit from optimal supportive therapy.

7.
J Oncol Pharm Pract ; 28(7): 1659-1663, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2064604

ABSTRACT

INTRODUCTION: Bortezomib is proteasome inhibitor used in multiple myeloma treatment. The reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) during bortezomib-based therapy is a well-known adverse event. Antiviral prophylaxis is mandatory. Nevertheless, reports of herpesviral encephalitis are scarce. CASE REPORT: A 57-year-old multiple myeloma patient who during CyBorD protocol (Bortezomib, cyclophosphamide, and dexamethasone), after a transient suspension of antiviral prophylaxis presented progressive headaches unresponsive to conventional analgesics, asthenia, fever, episodic visual hallucinations, and vesicular lesions in the right supraorbital and frontal region. Herpetic encephalitis was diagnosed after detecting herpes zoster in cerebrospinal fluid. MANAGEMENT & OUTCOME: The patient was treated with acyclovir 500mg every 6 hours for 21 days, and subsequent valacyclovir prophylaxis achieving an excellent clinical evolution. Anti-myeloma treatment was changed to lenalidomide and dexamethasone achieving a durable complete response. Herpesviral encephalitis is a rare but severe complication associated with the use of Bortezomib, especially when patients did not receive acyclovir prophylaxis. However, a rapid detection based on the clinical suspicion, and the prompt start of treatment, may lead to overcome this adverse event.


Subject(s)
Amyloidosis , Antineoplastic Agents , Encephalitis, Herpes Simplex , Multiple Myeloma , Acyclovir/adverse effects , Amyloidosis/chemically induced , Amyloidosis/complications , Amyloidosis/drug therapy , Antineoplastic Agents/adverse effects , Antiviral Agents/adverse effects , Boronic Acids/adverse effects , Bortezomib/adverse effects , Dexamethasone/adverse effects , Encephalitis, Herpes Simplex/chemically induced , Encephalitis, Herpes Simplex/complications , Encephalitis, Herpes Simplex/drug therapy , Herpesvirus 3, Human/physiology , Humans , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Pyrazines
8.
Clinical Lymphoma, Myeloma and Leukemia ; 22(Supplement 2):S411, 2022.
Article in English | EMBASE | ID: covidwho-2062040

ABSTRACT

Context: CARTITUDE-2 (NCT04133636) Cohort A is assessing cilta-cel in lenalidomide-refractory patients with progressive MM after 1-3 prior LOT. Objective(s): To present updated results from CARTITUDE-2 Cohort A. Design(s): Phase 2, multicohort study. Patient(s): Lenalidomide-refractory patients with progressive MM after 1-3 prior LOT (PI and IMiD included) and no previous exposure to BCMA-targeting agents. Intervention(s): Single cilta-cel infusion (target dose 0.75x106 CAR+ viable T-cells/kg) after lymphodepletion Main Outcome Measure(s): Primary endpoint was minimal residual disease (MRD) negativity at 10-5. Management strategies were used to reduce risk of movement/neurocognitive adverse events (MNTs). Pharmacokinetics (PK) (Cmax/Tmax of CAR+T-cell transgene levels), cytokine release syndrome (CRS)-related cytokines over time, peak cytokine levels by response/CRS, association of cytokine levels with immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR+T-cell CD4/CD8 ratio by response/CRS/ICANS are being evaluated. Result(s): As of January 2022 (median follow-up [MFU] 17.1 months), 20 patients (65% male;median age 60 years;median 2 prior LOT;95% refractory to last LOT) received cilta-cel. Overall response rate was 95% (90% >=complete response;95% >=very good partial response). Median times to first and best response were 1.0 month and 2.6 months, respectively. All 16 MRD-evaluable patients achieved MRD negativity at 10-5. Median duration of response was not reached. At 12 months, event-free rate was 79% and progression-free survival rate was 75%. 95% of patients had CRS (gr3/4 10%);median time to onset was 7 days and median duration was 3 days. Neurotoxicity was reported in 30% of patients (5 gr1/2;1 gr3/4) and ICANS in 15% (all 3 gr1/2);1 patient had gr2 facial paralysis. No MNTs were observed. 1 death occurred due to COVID-19 (treatment-related), 2 due to progressive disease, and 1 due to sepsis (not treatment-related). Preliminary PK analyses showed peak CAR-T cell expansion at day 10.5;median persistence was 153.5 days. Conclusion(s): At MFU of 17.1 months, a single cilta-cel infusion resulted in deep and durable responses in lenalidomide-refractory MM patients with 1-3 prior LOT. We will present updated PK/cytokine/CAR-T subset analyses and clinical correlation to provide novel insights into biological correlates of efficacy/safety in this population. Copyright © 2022 Elsevier Inc.

9.
Chest ; 162(4):A488, 2022.
Article in English | EMBASE | ID: covidwho-2060607

ABSTRACT

SESSION TITLE: Not the Normal Host: Infections Still Matter SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: Community Acquired Respiratory Viruses (CARVs) are associated with poor outcome in Solid Organ Transplant (SOT) recipients. We reviewed some of these outcomes such as respiratory support, length of stay (LOS), ICU admission, steroid use & 30-day all-cause mortality. METHODS: Multihospital, single center, retrospective review of electronic health records from 01/01/2014-12/31/2019. RESULTS: 23 SOT recipients (M=20, F=3) who tested positive for CARVs were identified. SOT distribution was heart=2, kidney=4, liver=3, lung=11, heart-lung=1, lung-kidney=1 & heart-kidney=1. Mean age at admission was 60 years, average LOS was 8 days with 2 pts needing >2 weeks. 6 pts required intensive care unit;8 pts required supplemental oxygen support. 16 pts had infiltrates on chest imaging. 15 pts had a 90-day readmission with respiratory complaints. 8 pts had bronchoscopy & 20 had positive nasal swab. 3 pts had a negative nasal swab but positive Bronchoalveolar lavage (BAL) for CARV while 2 pts had negative BAL but positive nasal swab. CARV distribution was Rhinovirus 48%, Parainfluenza 29%, Metapneumovirus 12%, Respiratory syncytial virus 0.03%, Adenovirus 0.03% & Non-novel Coronavirus 0.06%. 5 pts had bacterial coinfection (Pseudomonas aeruginosa, Corynebacterium striatum & Stenotrophomonas maltophilia). All pts were immunosuppressed, intravenous immunoglobulins (IVIG) were used in 3 pts, antivirals in 7 pts (ribavirin in 6 & oseltamivir in 1) & steroids in 10 pts. 12 pts had transplant organ biopsy with 5 showing acute cellular rejection. 11 pts had underlying Coronary artery disease and 17 pts had hematologic disorders (Post-transplant lymphoproliferative disorder, leukemia, Myelodysplastic syndrome, & multiple myeloma). 35% pts died within 1 year (2 during same admit). Cause of death was refractory septic shock (1), respiratory failure (3), cardiac arrest (3) & chronic lung allograft dysfunction (CLAD) (1). CONCLUSIONS: In this cohort, we assessed the SOT recipients positive for CARVs who required admission & evaluated the impact on their clinical course. This analysis noted a significant rate of acute & chronic rejections, bronchiolitis obliterans and CLAD in these patients. Newer tests like multiplex NAT & (semi) quantitative NAT (QNAT) can diagnose CARVs in addition to Human Influenza Virus. Patients can present with wheezing, croup, bronchiolitis, pneumonitis & pneumonia. Impact of CARVs seems to vary by the type of organ transplant, level of neutropenia/lymphopenia, upper versus lower respiratory infection and intrinsic pathogenicity of virus. Various preventive & therapeutic measures were employed in an attempt to improve outcomes in these patients. CLINICAL IMPLICATIONS: Transplant receipients are at a high risk of infections especially CARVs which may increase morbidity and mortality. This analysis emphasizes the value of timely diagnosis and treatment in this specific patient population who are immunocompromised. DISCLOSURES: No relevant relationships by Supriya Singh

10.
The British Journal of General Practice : The Journal of the Royal College of General Practitioners ; 72(723):462, 2022.
Article in English | ProQuest Central | ID: covidwho-2055439

ABSTRACT

Smith et al describe the issues with the current diagnostic process for myeloma in general practice, explore the potential impact of the COVID-19 pandemic, and identify alternative strategies that may improve the early diagnosis. Around half of myeloma patients have three or more pre-referral consultations and around one-third are diagnosed through emergency presentation. Improving the timeliness of myeloma diagnosis is vital to improving patient outcomes, but is difficult to achieve because of complex, non-specific, and varied presentations. Improving GP education on the salient features of multiple myeloma presentation and the investigations required for diagnosis, alongside ensuring adequate safety netting for patients with persistent, unexplained symptoms, should be urgent priorities. Changes to general practice consultations following the COVID-19 pandemic have made myeloma diagnosis more difficult, and, over the longer term, research is required to develop intelligent and technological strategies that support physician decision making and reduce diagnostic delay.

11.
Ter Arkh ; 94(7): 827-835, 2022 Aug 12.
Article in Russian | MEDLINE | ID: covidwho-2044341

ABSTRACT

AIM: The primary objective of the interim analysis of the MULTISPECT study was to evaluate the short-term efficacy of the treatment and long-term outcomes in cohorts of primary and pretreated patients with multiple myeloma (MM) receiving treatment in actual clinical practice in various regions of the Russian Federation. Secondary objectives were a description of the main characteristics of patients; analysis of the most commonly used therapy regimens of the 1st and later lines and the sequence of their changes; evaluation of the response to therapy. Additional objectives included evaluation of the effect of the new COVID-19 coronavirus infection on the course of MM in patients. MATERIALS AND METHODS: The study is an observational retrospective-prospective multicenter cohort study. For its implementation, a structured database of patients with MM was used, provided by hematologists of the centers affiliated for the study. RESULTS: The study included 1,294 patients (cohort 1 806, cohort 2 488). In both cohorts, patients aged 6069 years were in the majority. 3 lines of therapy (L1, L2, L3) were used for cohort 1; in cohort 2, the 4th line of therapy was also used in 2 patients. The therapy regimens were analyzed for 290 (22.41%) of all patients in the study. Responses to therapy were analyzed for 214 patients of cohort 1 and 109 patients of cohort 2. Autologous and allogeneic hematopoietic stem cell transplantations were carried out for a limited proportion of patients in both cohorts. At the end of the study and upon presentation of its results, the status of patients was the following: 96% of patients in cohort 1 and 89% in cohort 2 were alive. The therapy regimens in both cohorts were characterized by variability. The most commonly used regimens in each of the lines of therapy have been identified. The most used therapy regimen in patients with MM of both cohorts was the VCD-regime. Rd-regime in cohort 1 and RD-regime in cohort 2 were the second most frequent used regimens. In patients of both cohorts, the therapy regimens including Bortezomib were most often used. CONCLUSION: The variety of therapy regimens used to treat MM in actual clinical practice may be due to the factors of availability of new medicines and updated recommendations for the treatment of the disease. Further, in the context of this study, a more detailed analysis of the efficacy of certain therapy regimens in the 1st and later lines on progression free survival and overall survival of MM patients should be carried out.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Humans , Multiple Myeloma/diagnosis , Multiple Myeloma/epidemiology , Multiple Myeloma/therapy , Bortezomib/therapeutic use , Retrospective Studies , Cohort Studies , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/therapy , Transplantation, Autologous/methods , Hematopoietic Stem Cell Transplantation/methods , Treatment Outcome , Disease-Free Survival
12.
Clinical Lymphoma Myeloma and Leukemia ; 22:S413, 2022.
Article in English | ScienceDirect | ID: covidwho-2042281

ABSTRACT

Context: Triple class exposed/refractory multiple myeloma (MM) represents an unmet medical need because there is no standard of care and overall survival (OS) does not exceed 9 months. B-cell maturation antigen (BCMA) has appeared as an interesting target to treat MM. Objective: To indirectly compare the time to access therapy and hospitalization as well as the toxicity and efficacy of BCMA bispecific monoclonal antibodies (BiAbs) and CAR-T. Design: An observational retrospective study was designed including MM patients treated with BCMA CAR-T or BiAbs in clinical trials at the Hospital of Salamanca (October 2018–April 2022). Patients or Other Participants: Forty-nine patients were treated with BCMA therapy. Intervention: N/A. Main Outcome Measures: The time to access the treatment and hospitalization, global responses, cytokine release syndrome (CRS), neurotoxicity, infections, progression-free survival (PFS), and OS. Results: Twenty-seven patients (55.1%) received CAR-T and 22 (44.9%) received BiAbs. Thirty-nine (79.6%) patients were triple exposed and 28 (57.1%) were triple refractory. Patients who received BiAbs were treated earlier (12 vs. 56 days;P<0.001) and were hospitalized for less time (13 vs. 21 days;P=0.018). Overall response rate was superior in CAR-T patients (100% vs. 52.4%;P<0.001) as was percentage of CR (70.4% vs. 47.6%;P=0.110). Incidence of CRS was higher in the CAR-T group than the BiAbs group (92.6% vs. 68.2%;P=0.028) as were the percentages of grade 4 neutropenia (92.6% vs. 22.7%;P<0.001) and thrombocytopenia (70.4% vs. 9.1%;P<0.001). Infections were more frequent in the BiAbs group (especially between the first and third month of treatment initiation, 55.6% vs. 14.8%;P=0.004), including COVID-19 infection (50.0% vs. 29.6%;P=0.002). With a median follow-up of 14.3 months (1.1–41.8), PFS was superior in patients treated with CAR-T (18.9 vs. 6.1 months;P=0.045) as was OS (not reached vs. 25.5 months;P=0.016). Conclusions: The times to access therapy and hospitalization were shorter in patients treated with BiAbs. The incidences of CRS and cytopenia were higher in the CAR-T group, but mid-term and COVID-19 infections were more frequent in the BiAbs group. Response, PFS, and OS were superior in patients treated with CAR-T than those treated with BiAbs.

13.
Clinical Lymphoma Myeloma and Leukemia ; 22:S411, 2022.
Article in English | ScienceDirect | ID: covidwho-2042280

ABSTRACT

Context: CARTITUDE-2 (NCT04133636) Cohort A is assessing cilta-cel in lenalidomide-refractory patients with progressive MM after 1–3 prior LOT. Objective: To present updated results from CARTITUDE-2 Cohort A. Design: Phase 2, multicohort study. Patients: Lenalidomide-refractory patients with progressive MM after 1–3 prior LOT (PI and IMiD included) and no previous exposure to BCMA-targeting agents. Interventions: Single cilta-cel infusion (target dose 0.75×106 CAR+ viable T-cells/kg) after lymphodepletion Main Outcome Measures: Primary endpoint was minimal residual disease (MRD) negativity at 10-5. Management strategies were used to reduce risk of movement/neurocognitive adverse events (MNTs). Pharmacokinetics (PK) (Cmax/Tmax of CAR+T-cell transgene levels), cytokine release syndrome (CRS)-related cytokines over time, peak cytokine levels by response/CRS, association of cytokine levels with immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR+T-cell CD4/CD8 ratio by response/CRS/ICANS are being evaluated. Results: As of January 2022 (median follow-up [MFU] 17.1 months), 20 patients (65% male;median age 60 years;median 2 prior LOT;95% refractory to last LOT) received cilta-cel. Overall response rate was 95% (90% ≥complete response;95% ≥very good partial response). Median times to first and best response were 1.0 month and 2.6 months, respectively. All 16 MRD-evaluable patients achieved MRD negativity at 10-5. Median duration of response was not reached. At 12 months, event-free rate was 79% and progression-free survival rate was 75%. 95% of patients had CRS (gr3/4 10%);median time to onset was 7 days and median duration was 3 days. Neurotoxicity was reported in 30% of patients (5 gr1/2;1 gr3/4) and ICANS in 15% (all 3 gr1/2);1 patient had gr2 facial paralysis. No MNTs were observed. 1 death occurred due to COVID-19 (treatment-related), 2 due to progressive disease, and 1 due to sepsis (not treatment-related). Preliminary PK analyses showed peak CAR-T cell expansion at day 10.5;median persistence was 153.5 days. Conclusions: At MFU of 17.1 months, a single cilta-cel infusion resulted in deep and durable responses in lenalidomide-refractory MM patients with 1–3 prior LOT. We will present updated PK/cytokine/CAR-T subset analyses and clinical correlation to provide novel insights into biological correlates of efficacy/safety in this population.

14.
JMIR Cancer ; 8(3): e39068, 2022 Sep 22.
Article in English | MEDLINE | ID: covidwho-2039600

ABSTRACT

BACKGROUND: The patient experience of multiple myeloma (MM) is multifaceted and varies substantially between individuals. Current published information on the patient perspective and treatment of MM is limited, making it difficult to gain insights into patient needs regarding the condition. OBJECTIVE: In this review, a combined research method approach (ie, the review of published literature and social media posts) was undertaken to provide insight into patients' perspectives on the burden and treatment of MM, the impact of the COVID-19 pandemic, and the impact of MM on caregivers of patients with MM. METHODS: Targeted searches of PubMed and PsycINFO were conducted from November 16, 2010, to November 16, 2020; in parallel, patient-reported information derived from social media posts from 6 patient advocacy websites and YouTube were searched. The review of patient advocacy websites and YouTube targeted patient-reported information from patients with a self-reported diagnosis of MM who discussed their experience of MM and its treatments. RESULTS: A total of 27 articles and 138 posts were included (patient-reported information included data from 76 individuals), and results from both sources showed that patients experienced a variety of symptoms and treatment side effects, including neuropathy, fatigue, nausea, and back pain. These can affect areas of health-related quality of life (HRQOL), including physical functioning; emotional, psychological, and social well-being; the ability to work; and relationships. Patients valued involvement in treatment decision-making, and both the patient-reported information and the literature indicated that efficacy and tolerability strongly influence treatment decision-making. For patients, caregivers, and physicians, the preference for treatments was strongest when associated with increased survival. Caregivers can struggle to balance care responsibilities and jobs, and their HRQOL is affected in several areas, including emotional-, role-, social-, and work-related aspects of life. The COVID-19 pandemic has challenged patients' ability to manage MM because of limited hospital access and restrictions that negatively affected their lives, psychological well-being, and HRQOL. Unmet patient needs identified in the literature and patient-reported information were for more productive appointments with health care professionals, better-tolerated therapies, and more support for themselves and their caregivers. CONCLUSIONS: The combination of published literature and patient-reported information provides valuable and rich details on patient experiences and perceptions of MM and its treatment. The data highlighted that patients' HRQOL is impeded not only by the disease but also by treatment-related side effects. Patients in the literature and patient-reported information showed a strong preference for treatments that prolong life, and patients appeared to value participation in treatment decisions. However, there remain unmet needs and areas for further research, including treatment, caregiver burden, and how to conduct appointments with health care professionals. This may help improve the understanding of the journey of patients with MM. PLAIN LANGUAGE SUMMARY: Multiple Myeloma (MM) is the second most common cancer that affects blood cells. In this study, researchers wanted to know patients' views on the effects of MM and the treatments they received. Researchers also looked at the impact of the COVID-19 pandemic on patients' treatment and the impact of MM on caregivers. To this end, the researchers reviewed information from 27 published studies and 138 social media posts by 76 patients with MM. Patients commonly reported nerve pain, tiredness, feeling sick, and back pain caused by MM and the treatments they received. The effects of MM and treatments affected patients' physical function; emotional, psychological, and social well-being; ability to work; and relationships. The researchers found that patients wanted to be involved in decisions related to their treatment. The effectiveness against MM and known negative effects strongly influenced the choice of treatments for patients. Increased survival was the strongest factor in the choice of treatment for patients, caregivers, and doctors. Researchers found that the emotional-, role-, social-, and work-related aspects of caregivers' lives were affected by caring for patients with MM. The COVID-19 pandemic also affected the ability of patients to manage their MM because of limited hospital access and the effects of restrictions that impacted their lives and psychological well-being. Finally, the researchers identified some areas requiring improvement, including unproductive appointments with health care professionals, the need for treatments with fewer negative effects, and more support for patients with MM and their caregivers. This information may be useful to improve and understand the experience of patients with MM.

15.
HemaSphere ; 6:1647-1648, 2022.
Article in English | EMBASE | ID: covidwho-2032170

ABSTRACT

Background: Lenalidomide (LEN) maintenance and continuous LEN-based induction therapy until disease progression have become standard of care for frontline therapy of multiple myeloma (MM). As such, an increasing number of patients (pts) in need of 2nd line therapy have LEN-refractory disease. Optimal treatment in this setting has not been rigorously assessed in randomized studies. The phase I portion of Alliance A061202 demonstrated the safety of the ixazomib-pomalidomide-dexamethasone (IXA-POM-DEX) combination for the treatment of pts with LEN and proteasome inhibitor (PI)-refractory MM. Aims: In the randomized phase II portion, we evaluated the addition of IXA to POM-DEX for PI naïve / sensitive pts progressing on LEN as part of 1st line therapy. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall response rate (ORR), depth of response, survival and safety. Methods: Pts were randomized 1:1 to IXA-POM-DEX or POM-DEX and stratified by prior bortezomib exposure, International Staging System stage (1 and 2 vs 3) and the presence of high-risk cytogenetics. POM was administered at 4 mg on days 1-21;IXA 4 mg on days 1, 8 and 15;and DEX 20 mg (>75 years (yrs)) or 40 mg (≤75 yrs) on days 1, 8, 15 and 22 of a 28-day cycle. Treatment was continued until disease progression, the emergence of unacceptable side effects or withdrawal of treatment consent. Results: 38 and 39 eligible pts were assigned to IXA-POM-DEX and POM-DEX, respectively. The median age was 66 yrs (range 41-83) and 64 yrs (range 52-85). A planned first interim analysis was conducted after 43 out of 57 required events had occurred. PFS favored the IXA-POM-DEX arm (one-sided log rank test value = 4.6345, p=0.03134 [< p-value boundary of 0.058]), yielding a hazard ratio of 0.528 (upper 90% bound = 0.777). A stratified log-rank test found that PFS was superior for the triplet after adjusting for stratification factors (one-sided stratified log rank test value = 5.8371;p=0.0157), adjusted hazard ratio 0.451 (upper 90% bound = 0.694). The ORR favored IXA-POM-DEX (63.2% vs 43.6%, p=0.0853), and the ≥very good partial response was 26.3% vs 5.1%, respectively (p=0.01). The clinical benefit rate (ORR + minimal response rate) was 73.7% and 56.4%. The most common grade 3/4 adverse events included lymphopenia, neutropenia, anemia, and fatigue in 40%, 37%, 16% and 16% of IXAPOM-DEX-treated pts and 26%, 21%, 13%, and 15% of POM-DEX-treated pts. Therapy was discontinued for disease progression in 47.4% of pts on IXA-POM-DEX and 76.9% of pts on POM-DEX and for adverse events in 7.9% and 7.7% of pts, respectively. Summary/Conclusion: The addition of IXA to the POM-DEX backbone improved the depth of response and PFS for pts relapsing on LEN as part of 1st line therapy. Hematologic toxicity was increased with the addition of IXA, but side effects were manageable. The ease of administration of this all-oral combination allowed for safer, uninterrupted treatment during the COVID pandemic. Our results should be confirmed in phase III trials but lend support for this regimen as part of 2nd line therapy for this patient population.

16.
HemaSphere ; 6:1596-1597, 2022.
Article in English | EMBASE | ID: covidwho-2032166

ABSTRACT

Background: The bortezomib, lenalidomide, and dexamethasone (VRd) regimen is a standard of care for newly diagnosed multiple myeloma (NDMM). Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate that eliminates myeloma cells by a multimodal mechanism: direct cell kill and anti-myeloma tumor immune response. Belamaf has demonstrated deep and durable responses as a monotherapy in the DREAMM-2 study of patients (pts) with relapsed/refractory multiple myeloma (RRMM). Preclinical evidence of belamaf in combination with bortezomib or lenalidomide suggests enhanced anti-myeloma activity, providing rationale for this treatment combination. Aims: To evaluate the safety and tolerability of this combination in adult pts with transplant-ineligible (TI) NDMM and establish the recommended Phase III dose. Methods: DREAMM-9 (NCT04091126) is an ongoing Phase I, open-label, randomized study of belamaf + VRd. The belamaf dose cohorts currently being evaluated are Cohort 1 (1.9 mg/kg Q3/4W), Cohort 2 (1.4 mg/kg Q6/8W), Cohort 3 (1.9 mg/kg Q6/8W), Cohort 4 (1.0 mg/kg Q3/4W), and Cohort 5 (1.4 mg/kg Q3/4W). Belamaf is given with VRd Q3W until Cycle 8, and with Rd Q4W thereafter. After evaluation of safety data for Cohort 1, Cohorts 2-5 were opened in parallel and enrolled pts were randomized 1:1:1:1. Primary endpoint is safety. Secondary endpoints include efficacy, tolerability, and pharmacokinetics (PK). Results: As of data cutoff (07 Dec 2021), 64 pts were analyzed across all cohorts. Median age (range) was 73.0 (51- 88) years, 55% were male, 80% were white, 8% had extramedullary disease, 59% were International Staging System stage II or III, 20% had amp1q, and 17% had high-risk cytogenetics (≥1 of: t(4;14), t(14;16), del17p). The median duration of follow-up varied: Cohort 1 (17.4 months [mo]), Cohort 2 (5.9 mo), Cohort 3 (6.1 mo), Cohort 4 (4.7 mo), Cohort 5 (5.8 mo). Median number of belamaf cycles were: Cohort 1 (6), Cohort 2 (3), Cohort 3 (3.5), Cohort 4 (4.5), and Cohort 5 (5). Most common adverse events (AEs) across cohorts included thrombocytopenia (49%), constipation (43%), diarrhea (32%), and peripheral sensory neuropathy (30%). AEs related to study treatment were experienced by 61 (97%) pts. Belamaf-related grade 3/4 AEs occurred in 24 (38%) pts. Belamaf dose reductions occurred in 11 (18%) pts, with dose delays in 10 (16%) pts. Three pts experienced a fatal severe AE (unrelated to study treatment);2 due to COVID-19 infection, 1 due to pancreatic adenocarcinoma. Early deep responses were observed;67-92% pts achieved ≥very good partial response (VGPR) (Table), with median time to VGPR of 2.1-2.9 months across cohorts. Of pts with ≥VGPR, 17 were minimal residual disease (MRD) negative, 10 in Cohort 1. As of data cutoff, 8-75% of pts achieved best response of complete response (CR) or stringent CR (sCR). Grade 3 corneal exam findings were reported in 25-58% of pts;grade 3 visual acuity changes were reported in 21-75% of pts. No grade 4 corneal exam findings or visual acuity changes were reported in pts receiving belamaf Q6/8W, compared with 0-17% and 0-8%, respectively, in the Q3/4W cohorts. Belamaf PK profile was similar to that in pts with RRMM, accounting for baseline characteristics. Image: Summary/Conclusion: Belamaf + VRd demonstrated high response rates in pts with TI NDMM, with a high rate of MRD negativity indicating deep responses. No new safety signals were observed relative to DREAMM-2. Study is ongoing to evaluate the safety and efficacy of variable dose intensities of belamaf in combination with VRd.

17.
HemaSphere ; 6:161, 2022.
Article in English | EMBASE | ID: covidwho-2032164

ABSTRACT

Background: High-risk (HR) cytogenetic is associated with poor outcome in transplant eligible (TE) newly diagnosed myeloma multiple myeloma (NDMM). The triplet combination carfilzomib lenalidomide and dexamethasone (KRD) plus transplantation demonstrated high efficacy with faorable safety profile in TE-NDMM patients (FORTE). The addition of daratumumab (Dara) to frontline therapy also improed response rate and progression free-surial in TE-NDMM patients (CASSIOPEIA, GRIFFIN). Double transplant also improed outcome of HR TE NDMM patients (EMN02, STAMINA). Aims: The phase 2 trial 2018-04 from the Intergroupe Francophone du Myelome (IFM) is ealuating an intensie strategy with Dara-KRD induction and consolidation plus double transplant in HR TE NDMM (NCT03606577). Methods: HR MM was defined by the presence of del17p, t(4;14) and/or t(14;16). Stategy includes Dara-KRD induction (6 cycles), autologous stem cell transplantation (ASCT), Dara-KRD consolidation (4 cycles), second ASCT, Dara-lenalidomide maintenance. The primary endpoint was the feasibility of this intensie strategy. Here, we report efficacy and safety analysis of Dara-KRD induction. Results: Fifty patients with preiously untreated NDMM were included from july 2019 to march 2021 in 11 IFM centers Median age was 57 (range 38 -65). ISS stage 3 was present in 12 (24%) patients. Based on inclusion criteria, all patients had HR cytogenetic, including 17p deletion (n=20, 40%), t(4;14) (n=26, 52%) or t(14;16) (n=10,20%). Forty-six patients completed Dara-KRD induction. Two patients discontinued treatment due to seere aderse eent (COVID-19 infection, n=1 ;drug-induced hepatitis, n=1) and 2 patients discontinued treatment due to disease progression. Grade 3-4 treatment related aderse eent (>5% of patients) were neutropenia (38%), anemia (14%), thrombocytopenia (8%), infection (6%), renal insufficiency (6%) and deep-ein thrombosis (6%). Two patients (6%) experienced stem-cell collection failure. Oerall response rate was 96%, including 92 % > ery good partial response. Among 37/46 ealuable patients post induction, Minimal Residual Disease negatiity rate (NGS, 10-5) was 62%. Summary/Conclusion: Dara-KRD as induction prior ASCT is safe and allows deep responses in TE NDMM patients with high-risk cytogenetic profile. IFM 2018-04 study is ongoing and longer follow-up is needed to ealuate safety and efficacy of the oerall strategy with Dara-KRD induction and consolidation plus double transplant in this subset of HR patients.

18.
HemaSphere ; 6:4042-4043, 2022.
Article in English | EMBASE | ID: covidwho-2032160

ABSTRACT

Background: Special epidemiological measures aimed at suppressing SARS-CoV-2 outbreak were introduced in Croatia in March 2020, thus reducing regular work capacity in hematological outpatient and inpatient care. In our hospital, this included relocating the entire Hematology Department to a remote location, reduction of hospital beds in the Hematology Inpatient Unit by approximately 60%, Day Clinic operating at a reduced capacity, and a complete suspension of Hematology Polyclinic during first lockdown. Aims: Herein we report our observation of unusually high incidence of newly diagnosed malignant hematological diseases following first lockdown ease in May/June 2020. Methods: We collected data of patients hospitalized in Hematology Department for 4 periods: May 1 - June 15, 2020 for the test arm, and the same calendar period during previous 3 years (May 1 - June 15 of each of the calendar years 2017, 2018 and 2019), for the control arm. The rationale for such design was that a phenomenon of re-establishing regular work capacity, following temporary restriction, was only observed in the test arm. The study included patients of both sexes older than 18 who were diagnosed with either: Hodgkin lymphoma (C81.0 -C81.9 according to the 10th ICD Revision), different types of non-Hodgkin lymphoma (subsections C82.0 - C83.9 and C85.1-C85), as well as multiple myeloma and malignant plasma cell neoplasms (C90.0 - C90.3). Excluded from our study were diagnoses of T/NK cell lymphoma (C84.0- C84.9;C86.0 - C86.6), malignant immunoproliferative diseases (C88.0 - C88.9), leukemias and other specified malignant neoplasms of lymphatic, hematopoietic and related tissues (C91.0 - C96.9) as well as polycythemia vera and non-malignant hematological diseases (D45 and D50 - D89 in ICD-10). Results: In years 2017-2019, similar numbers of patients were diagnosed with a hematological malignancy in our Department (n=4 for 2017, n=8 for 2018, n=4 for 2019) whereas in 2020, a total of 28 patients were diagnosed during the same calendar period (Hodgkin lymphoma: n=5, NHL n=12, multiple myeloma n=7, CLL/SLL n=4). Statistical analysis revealed a significant increase (p ≤0.05) of newly diagnosed hematological malignancies in May and first half of June 2020, when compared to the same calendar periods during previous three years. Further statistical analysis has not established significant differences in outcome (difference in EFS statistically insignificant, p=0.86), as we had expected in the short follow-up period. (Table Presented) Summary/Conclusion: Facilitating treatment of patients affected by the novel coronavirus represented a welcome change in healthcare system in early 2020, in our country and abroad. At the same time, however, the reduction of tertiary health care capacity aimed at population with hematological diseases presented serious risks for successful diagnosis and treatment outcome, a subject that gained wide attention in literature. It has been reported that, also due to psychological reasons, a fraction of patients delayed seeking medical attention after noticing symptoms. In our study we aimed at analyzing the effects of lockdown ease on the number of newly diagnosed hematological malignancies. We were able to demonstrate the effect of pandemic-related measures on detecting new disease cases. It remains to be clarified if a sudden surge in new diagnoses was due to delayed first physician's appointments/hospitalizations, as is suggested by available literature. The results of our study suggest that longer follow-up period will be required in order to clarify the effects of possible late diagnoses on the treatment outcome.

19.
HemaSphere ; 6:3503-3504, 2022.
Article in English | EMBASE | ID: covidwho-2032142

ABSTRACT

Background: Despite therapeutic strategies improvement, there is still a subgroup of NDMM patients (pts) that pose a clinical challenge, whose represents a <20%, we refer to HRC. HRC Pts are associated with a poor prognosis and aggressive course, although, recent studies propose different clinical evolution according to the cytogenetic alteration (CA). IMWG identified a 4-year progression free survival (PFS) of 12% and OS of 35%. Aims: Describe our clinical experience and therapeutic management, also the clinical-biochemical alterations at diagnosis in a heterogeneous NDMM HRC's cohort. Evaluate survival curves according to HRC. Methods: Descriptive and retrospective analysis, using clinical and analytical NDMM HRC patient's data from 2009 to 2022 at Guadalajara University Hospital. 61/201 pts were selected in the MM treatment (tto) protocols. FISH results were not found in <30% NDMM, due to lack of metaphases or no request. Pts with t(4;14), t(14;16), gain 1q, t(14;20), plasmablastic leukemia and/or del(17p13) were classified as HRC. Survival data and Pearson (P) correlation were used. P value <0.05 was considered significant. Results: Total HRC NDMM 61 pts were analyzed. 21 of 61 pts (35%) were diagnosed with stage monoclonal gammopathy of undetermined significance (MGUS) prior to HRC NDMM, with a mean 4 years (y) (IR 2-10 y), greater % representation of MGUS were del17p (38), gain 1q (48), t (14;16) (4,5) and del17p + gain1q (9,5). Clinical characteristics data at diagnosis according to HRC are shown in Table 1. Pts receiving 1st line were 100% (61), 90,2% of the pts received bortezomib (V) - based induction, of them 29% (n=16) were treated with alkylating agents, 49,1% (n=27) received IMIDs and 18,2% (n=10) V with dexamethasone (d), plus two of these pts received regimens composed of 3xVCd + 3xVPd and the other dara-VRd. 25 pts (40,98%) were transplant eligible (TPH). 2nd line, 32 pts (52,5%), (n=3) VTD-PACE, (n=6) daratumumab (n=1 alone, 3 R, 1 V, 1 K), (n=1) Kdexa, (n=1) Pocydex and (n=9) V plus 3 IMIDs, 2 alkylating, 2 P or 2 alone and (n=12) IMIDs and alkylatings in combination. 5 pts (8,2) were TPH (1 alogenic). 3rd line, 16 pts (26,2), just 3 pts were TPH. 4th line, 7 pts (11,4), 1 pts were TPH. 5th line, 4 pts (6,5). 6th line, 2pts (3,3). In the last lines, the use of triplets with pomalidomide, karfilzomib or intensive chemotherapy prevail. After a median follow-up of 3 y (IR 1,6-6,2) from diagnosis, pts had relapsed at least one time (60,6%) and more than 3 times (11,5%), and 25 had died (40,9%), 16 of them due to infections (14 bacteremia, 2 COVID), 5 cardiorespiratory arrest and 3 due to progression. (Image 1) represents PFS y OS for only 5 CA, as data were no representative in other CA. Correlation between ISS and ISS-R data were only able to execute in HRC gain1q, due to lack of sample in other CA. We found a P coefficient of 0.568399 or 56.83% (p- <0.00578, CI 95%). Summary/Conclusion: Our case series continues with a longer survival curve compared to those commented in other studies. As cytogenetic abnormalities (t(4;14), t(14;16), t(14;20) and gain1q), similar % of representation are described as Kumar. Nat Rev Clin Oncol. 2018, except for del(17p), 23% vs 10%. From the second line, the probability of receiving a new line, the duration of tto and the interval without tto decreased with each line of tto. As treatment lines progress, therapeutic combinations are more heterogeneous and less concordant. A further longer follow-up and higher HRC NDMM pts's recruitment will be necessary to clarify the response to tto regimens based on individual cytogenetic groups.

20.
HemaSphere ; 6:1067-1068, 2022.
Article in English | EMBASE | ID: covidwho-2032135

ABSTRACT

Background: Patients with lymphopproliferative diseases (LPD) and covid-19 have poor outcome as consequence of inadequate humoral and cellular immunity due to the hematological disease itself but also due to the administered chemotherapy which further increases the risk of complications and mortality. Aims: The aim of this study is to analyze demographic and clinical characteristics, laboratory parameters, the presence of comorbidities, laboratory parameters, disease status, as well as outcome of the patients with COVID-19 and lymphoproliferative disease and compare them with characteristics of covid-19 infection in patients from general population (GP). Methods: This is a prospective multicenter observational study conducted in the following 3 University centers in period from 15 March 2020 to 31 October 2021. The study included hospitalized patients diagnosed with COVID-19 infection: 161 patients with LPD and 162 patients from the GP. Statistical analysis included demographic statistics, the χ2 test, the Mann-Whitney test, Kaplan-Meier method for analysis of survival and multivariate logistic regression model for analysis of risk factors for mortality. Results: In the LPD group, there were 54 patients (33.54%) with chronic lymphocytic leukemia (CLL), 72 patients (44.72%) with Non-Hodgkin lymphoma/Hodgkin lymphoma (NHL/HL) and 35 patients (21.74%) with multiple myeloma (MM). Ninety-six (59,63%) patients were on active treatment and 14(8.7%) patients were newly diagnosed. The LPD and GP group differed significantly in relation to age (66 vs. 54 years), gender (male: 60.2% vs. 75.3%), presence of comorbidities (109, 67.7% vs. 81, 50%) patients, covid score (mild 22.5% vs. 1.9%, moderate 80, 50.3% vs. 121, 74.7%), and severe/critical 44(27.1%) vs. 38(23.4%) patients. Group of patients with LPD had also significantly lower level of hemoglobin, lowest value of lymphocytes, platelets, higher level of CRP, ferritin, Ddimer (on admission and maximal values) and LDH with respect to group of patients from GP. Mortality rate was higher in LPD group of patients than in GP group (45, 28% vs. 26, 16%) patients. Among the LPD group, the highest mortality rate was observed in patients with MM (16, 45.71%) patients, followed by CLL (15, 27.9%) patients and NHL/HL group (14, 19.4%) patients. Independent factors related to survival are high value of D dimer, anemia (hemoglobin <100g/l) and moderate/critical COVID score in LPD group, while maximal value of CRP, anemia, leucocytosis and age (>60 years) in GP group. Summary/Conclusion: Our study showed significant difference in the characteristics and outcome in covid-19 between patients with LPD and patients from GP. Patients with LPD are older, they have significantly higher inflammatory parameters and more frequent presence of comorbidities compared to patients from GP. Independent factors related to survival in the LPD group are high values of D dimer, moderate/critical COVID score and anemia, while maximal values of CRP, anemia and older age are identified in the GP group.

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