Variability in the perception of palliative care and end-of-life care among hematology professionals from the same reference center in Bahia, Brazil: A descriptive cross-sectional study.

BACKGROUND: There are several illness-specific cultural and system-based barriers to palliative care (PC) integration and end-of-life (EOL) care in the field of oncohematology. OBJECTIVES: This study aimed to investigate the variability in the perceptions of PC and EOL care. DESIGN AND SETTING: A cross-sectional study was conducted in the Hematology Division of our University Hospital in Salvador, Bahia, Brazil. METHODS: Twenty physicians responded to a sociodemographic questionnaire and an adaptation of clinical questionnaires used in previous studies from October to December 2022. RESULTS: The median age of the participants was 44 years, 80% of the participants identified as female, and 75% were hematologists. Participants faced a hypothetical scenario involving the treatment of a 65-year-old female with a poor prognosis acute myeloid leukemia refractory to first-line treatment. Sixty percent of the participants chose to follow other chemotherapy regimens, whereas 40% opted for PC. Next, participants considered case salvage for the patient who developed septic shock following chemotherapy and were prompted to choose their most probable conduct, and the conduct they thought would be better for the patient. Even though participants were from the same center, we found a divergence from the most probable conduct among 40% of the participants, which was due to personal convictions, legal aspects, and other physicians' reactions. CONCLUSIONS: We found considerable differences in the perception of PC and EOL care among professionals, despite following the same protocols. The study also demonstrated variations between healthcare professionals' beliefs and practices and persistent historical tendencies to prioritize aggressive interventions.

Variability in the perception of palliative care and end-of-life care among hematology professionals from the same reference center in Bahia, Brazil: A descriptive cross-sectional study

ABSTRACT BACKGROUND: There are several illness-specific cultural and system-based barriers to palliative care (PC) integration and end-of-life (EOL) care in the field of oncohematology. OBJECTIVES: This study aimed to investigate the variability in the perceptions of PC and EOL care. DESIGN AND SETTING: A cross-sectional study was conducted in the Hematology Division of our University Hospital in Salvador, Bahia, Brazil. METHODS: Twenty physicians responded to a sociodemographic questionnaire and an adaptation of clinical questionnaires used in previous studies from October to December 2022. RESULTS: The median age of the participants was 44 years, 80% of the participants identified as female, and 75% were hematologists. Participants faced a hypothetical scenario involving the treatment of a 65-year-old female with a poor prognosis acute myeloid leukemia refractory to first-line treatment. Sixty percent of the participants chose to follow other chemotherapy regimens, whereas 40% opted for PC. Next, participants considered case salvage for the patient who developed septic shock following chemotherapy and were prompted to choose their most probable conduct, and the conduct they thought would be better for the patient. Even though participants were from the same center, we found a divergence from the most probable conduct among 40% of the participants, which was due to personal convictions, legal aspects, and other physicians' reactions. CONCLUSIONS: We found considerable differences in the perception of PC and EOL care among professionals, despite following the same protocols. The study also demonstrated variations between healthcare professionals' beliefs and practices and persistent historical tendencies to prioritize aggressive interventions.

COVID-19 in multiple myeloma patients: frequencies and risk factors for hospitalization, ventilatory support, intensive care admission and mortality -cooperative registry from the Grupo Brasileiro de Mieloma Multiplo (GBRAM).

INTRODUCTION: This study evaluated outcomes and risk factors for COVID-19 in 91 Brazilian multiple myeloma (MM) patients between April 2020 and January 2022. RESULTS: Of the 91 MM patients diagnosed with COVID-19, 64% had comorbidities and 66% required hospitalization due to COVID-19, with 44% needing ventilatory support and 37% intensive care. Age (OR 2.02; 95%CI 1.02 - 7.7) and hypertension OR 4.5; 95%CI 1.3 - 15.5) were independently associated with hospitalization and certain MM therapies (corticosteroids and monoclonal drugs) were associated with ventilatory support (OR 4.3; 95%CI 1.3 - 14 and OR 5.7; 95%CI 1.8 - 18, respectively), while corticosteroids and immunomodulatory drugs were linked to ICU admission (OR 5.1; 95% CI 1.4 - 18 and OR 3.4; 95%CI 1.1 - 10, respectively). The overall mortality rate was 30%, with the highest rate observed in the ICU (73%). Additionally, the ECOG performance status was linked to increased mortality (OR 11.5; 95%CI 1.9 - 69). The MM treatment was delayed in 63% of patients who recovered from COVID-19. CONCLUSIONS: The findings highlight the need for preventing COVID-19 and prioritizing vaccination among MM patients, as they have high rates of severe outcomes in the event of COVID-19. It is also essential to monitor the potential clinical impacts of COVID-19 on MM patients in the long-term. Given the limited resources available in treating MM patients in Brazil during the COVID-19 pandemic, outcomes might be worse in this population.

Outcome of Second Primary Malignancies Developing in Multiple Myeloma Patients.

BACKGROUND: There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational 'real-world' retrospective study analyzed the characteristics and outcomes of MM patients that developed SPMs. RESULTS: 165 patients were analyzed: 62.4% males; 8.5% with a prior cancer; 113 with solid SPMs, mainly ≥stage 2; and 52 with hematological SPM (hemato-SPM), mainly MDS/AML. Patients with hemato-SPM were younger (p = 0.05) and more frequently had a prior AutoHCT (p = 0.012). The time to SPM was shorter in the older (>65 years) and more heavily pretreated patients. One hundred patients were actively treated at the time of SPM detection. Treatment was discontinued in 52, substituted with another anti-MM therapy in 15, and continued in 33 patients. Treatment discontinuation was predominant in the patients diagnosed with hemato-SPM (76%). The median OS following SPM detection was 8.5 months, and the main cause of death was SPM. A poor ECOG status predicted a shorter OS (PS 3 vs. 0, HR = 5.74, 2.32-14.21, p < 0.001), whereas a normal hemoglobin level (HR = 0.43, 0.19-0.95, p = 0.037) predicted longer OS. CONCLUSIONS: With the continuing improvement in OS, a higher proportion of MM patients might develop SPM. The OS following SPM diagnosis is poor; hence, frequent surveillance and early detection are imperative to improve outcomes.

CAR-T cell therapy for multiple myeloma: a practical toolkit for treatment in Brazil.

INTRODUCTION: Chimeric antigen receptor T (CAR-T) cell therapy is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) that is a multi-step process involving various stakeholders. Appropriate education on the practical logistics is therefore paramount to ensure treatment success. METHODS: A group of key opinion leaders met to explore the key elements of setting up and running a CAR-T center in Brazil. For each step in the CAR-T cell therapy process, the experts agreed on basic requirements, gave their key recommendations from practical experience, and considered any remaining unanswered questions. RESULTS: This paper presents best-practice recommendations and advice on how to overcome common challenges for each step in the CAR-T cell therapy process, with a focus on the current situation in Brazil. Key themes throughout the process are collaboration within the multidisciplinary team and with the referring physician, along with communication and education for patients and their caregivers. CONCLUSION: We believe that the expert insights presented in this paper, in particular on optimal patient selection and timing of CAR-T cell therapy, will deepen understanding of the CAR-T process and aid implementation of this novel therapy for patients with RRMM in Brazil.

Impact of the lactate dehydrogenase in association with the International Staging System prognostic score in multiple myeloma patients treated in real life.

INTRODUCTION: Multiple myeloma is characterized by proliferation of clonal plasma cells. The identification of prognostics factors to identify patient's risk is important. Among the studied factors, it was identified of relevant importance the lactic dehydrogenase. OBJECTIVES: To evaluate the impact of the value of DHL in combination with the score ISS in the medium patients overall survival (OS). METHODS: It is a retrospective cohort with 252 patients with MM recently-diagnosed that attendance in the institution of the study. RESULTS: To evaluate the association between DHL and ISS, we found 6 new groups to be analyzed: ISS I and normal DHL with medium overall survival not reached, and with DHL loud with medium OS of 69,8 months, ISS II and normal DHL with medium overall survival of 78,8 months and with DHL loud with medium OS of 73,9 months, ISS III and normal DHL with medium overall survival of 46,7 months and with DHL loud with medium OS of 45,5 months. CONCLUSION: Through the association of ISS I and normal DHL, ISS III and high DHL and others combinations, we build a new score with superior impact prognostic in our population treated in real life.

CAR-T cell therapy for multiple myeloma: a practical toolkit for treatment in Brazil

ABSTRACT Introduction Chimeric antigen receptor T (CAR-T) cell therapy is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) that is a multi-step process involving various stakeholders. Appropriate education on the practical logistics is therefore paramount to ensure treatment success. Methods A group of key opinion leaders met to explore the key elements of setting up and running a CAR-T center in Brazil. For each step in the CAR-T cell therapy process, the experts agreed on basic requirements, gave their key recommendations from practical experience, and considered any remaining unanswered questions. Results This paper presents best-practice recommendations and advice on how to overcome common challenges for each step in the CAR-T cell therapy process, with a focus on the current situation in Brazil. Key themes throughout the process are collaboration within the multidisciplinary team and with the referring physician, along with communication and education for patients and their caregivers. Conclusion We believe that the expert insights presented in this paper, in particular on optimal patient selection and timing of CAR-T cell therapy, will deepen understanding of the CAR-T process and aid implementation of this novel therapy for patients with RRMM in Brazil.

Impact of the lactate dehydrogenase in association with the International Staging System prognostic score in multiple myeloma patients treated in real life

Abstract Introduction Multiple myeloma is characterized by proliferation of clonal plasma cells. The identification of prognostics factors to identify patient's risk is important. Among the studied factors, it was identified of relevant importance the lactic dehydrogenase. Objectives To evaluate the impact of the value of DHL in combination with the score ISS in the medium patients overall survival (OS). Methods It is a retrospective cohort with 252 patients with MM recently-diagnosed that attendance in the institution of the study. Results To evaluate the association between DHL and ISS, we found 6 new groups to be analyzed: ISS I and normal DHL with medium overall survival not reached, and with DHL loud with medium OS of 69,8 months, ISS II and normal DHL with medium overall survival of 78,8 months and with DHL loud with medium OS of 73,9 months, ISS III and normal DHL with medium overall survival of 46,7 months and with DHL loud with medium OS of 45,5 months. Conclusion Through the association of ISS I and normal DHL, ISS III and high DHL and others combinations, we build a new score with superior impact prognostic in our population treated in real life.

Lambda light chain-induced monoclonal gammopathy of renal significance, manifesting with Fanconi Syndrome and osteomalacia.

BACKGROUND: Monoclonal gammopathy of renal significance (MGRS) encompasses a heterogeneous group of kidney diseases in which a monoclonal immunoglobulin secreted by a clone of B cells or plasma cells causes kidney damage without meeting the hematological criteria for malignancy. Among the various forms of involvement, MGRS can manifest as a proximal tubule disorder, such as Fanconi syndrome (FS), characterized by urinary loss of phosphate, glucose, amino acids, uric acid and bicarbonate. Few cases of MGRS have been described in the literature, manifesting as FS and monoclonal production of lambda light chains, almost all of which are secondary to the production of kappa light chains. CASE PRESENTATION: Here we report a clinical case of a 45-year-old Brazilian male, African descent, with proximal weakness of the lower limbs, whose initial assessment showed a urine summary with the presence of proteinuria and glycosuria without hyperglycemia, associated with mild worsening of renal function, hypouricemia, hypocalcemia and phosphaturia. Evolution was characterized by a MGRS manifesting as FS and osteomalacia. CONCLUSION: The diagnosis of MGRS is not always easy, it requires knowledge of the clinical characteristics, diagnostic criteria and prognosis of each case. Therefore, all possible efforts should be made for multidisciplinary diagnosis.

Monoclonal gammopathy of renal significance (MGRS): Real-world data on outcomes and prognostic factors.

Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis-related to MGRS (MGRS-A) was present in 180 patients; nonamyloidosis MGRS (MGRS-NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0-121.0). Patients with MGRS-A had a shorter overall survival than patients with MGRS-NA (HR = 0.41, 95%CI: 0.25-0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04-115.96; p < 0.0001), one-fourth of patients with ≥VGPR were renal nonresponders. In MGRS-A, factors associated with poor prognosis included elevated levels of creatinine, beta-2-microglobulin, and hemodialysis at diagnosis. In MGRS-NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS.

POEMS Syndrome: Real World Experience in Diagnosis and Systemic Therapy - 108 Patients Multicenter Analysis.

POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present a retrospective real world experience of 108 patients with POEMS. We analyzed the clinical features and therapeutic interventions. Regarding clinical features, our findings demonstrated that skin lesions, thrombocythemia and polycythemia were present less frequently than reported previously. Regarding clinical interventions, this is one of the largest analyses of front line treatment in POEMS and the first one to include frequent utilization of proteasome inhibitors (37%). Bortezomib monotherapy was the most effective therapy achieving complete remission/very good partial remissions (CR/VGPR) in 69% of patients. Thirty percent of patients proceeded to planned autologous stem cell transplant (ASCT) as part of the front-line treatment resulting in statistically superior progression-free (PFS) and overall survival (OS) compared to non-ASCT treated patients (P= .003). In multivariate analysis, anemia, thrombocytopenia, and as age over 60 were associated with a negative impact on patient outcomes.

Results of the daratumumab monotherapy early access treatment protocol in patients from Brazil with relapsed or refractory multiple myeloma

ABSTRACT Introduction: Daratumumab is a CD38-targeting monoclonal antibody with established efficacy and safety in patients with relapsed or refractory multiple myeloma (RRMM). We report results of an early access protocol (EAP) of daratumumab monotherapy for RRMM in a cohort of Brazilian patients. Methods: Patients with RRMM and ≥3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or who were double refractory to both a PI and IMiD received daratumumab, 16 mg/kg, intravenously weekly for 8 weeks, biweekly for 16 weeks, and every 4 weeks thereafter until disease progression, unacceptable toxicity, loss of clinical benefit, or study conclusion or if daratumumab became available with reimbursement. Results: Forty-nine patients received ≥1 dose of daratumumab. The median (range) duration of treatment was 6.4 (0.3-11.8) months, with a median (range) of 8 (1-13) treatment cycles. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 38.8% of patients, most frequently neutropenia and pneumonia (10.2% each). Seven (14.3%) patients discontinued treatment due to TEAEs; 3 patients discontinued due to daratumumab-related TEAEs. Serious TEAEs occurred in 38.8% of patients. Infusion-related reactions were reported in 25 (51.0%) patients, were primarily grade 1/2, and the majority (23 patients) occurred during the first infusion. Twenty (40.8%) patients achieved a partial response or better; median progression-free survival was 8.25 (95% confidence interval, 5.55-17.54) months. Conclusion: In this EAP, daratumumab monotherapy in Brazilian patients showed a safety and efficacy profile consistent with clinical studies of daratumumab monotherapy in patients with heavily pretreated RRMM. ClinicalTrials.gov identifier: NCT02477891.

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. IV: CAR-T cell therapy for multiple myeloma patients.

Extraordinary progress has been made over the last decade in the treatment of multiple myeloma with the incorporation of new drugs, particularly proteasome inhibitors, immunomodulators, and monoclonal antibodies. The combined use of innovative drugs, already in the first lines of treatment, has led to an expressive increase in the survival of these patients. However, the approach to relapse remains a great challenge, and the disease continues to be incurable. In this scenario, modern immunotherapy has gained the limelight, especially with its recent use of CAR-T cells in clinical trials, as in the case of multiple myeloma, having the BCMA as the primary target. The results are impactful in the treatment of multiple myeloma patients who have had multiple relapses and are triple- and penta-refractory. In this Consensus, we have brought together a group of experts in multiple myeloma to discuss and forward their recommendations for the future, which we hope is very near, incorporating the CAR-T in our country.

Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis.

BACKGROUND: Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. METHODS: We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response. RESULTS: A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P<0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy. CONCLUSIONS: Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).

Results of the daratumumab monotherapy early access treatment protocol in patients from Brazil with relapsed or refractory multiple myeloma.

INTRODUCTION: Daratumumab is a CD38-targeting monoclonal antibody with established efficacy and safety in patients with relapsed or refractory multiple myeloma (RRMM). We report results of an early access protocol (EAP) of daratumumab monotherapy for RRMM in a cohort of Brazilian patients. METHODS: Patients with RRMM and ≥3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or who were double refractory to both a PI and IMiD received daratumumab, 16 mg/kg, intravenously weekly for 8 weeks, biweekly for 16 weeks, and every 4 weeks thereafter until disease progression, unacceptable toxicity, loss of clinical benefit, or study conclusion or if daratumumab became available with reimbursement. RESULTS: Forty-nine patients received ≥1 dose of daratumumab. The median (range) duration of treatment was 6.4 (0.3-11.8) months, with a median (range) of 8 (1-13) treatment cycles. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 38.8% of patients, most frequently neutropenia and pneumonia (10.2% each). Seven (14.3%) patients discontinued treatment due to TEAEs; 3 patients discontinued due to daratumumab-related TEAEs. Serious TEAEs occurred in 38.8% of patients. Infusion-related reactions were reported in 25 (51.0%) patients, were primarily grade 1/2, and the majority (23 patients) occurred during the first infusion. Twenty (40.8%) patients achieved a partial response or better; median progression-free survival was 8.25 (95% confidence interval, 5.55-17.54) months. CONCLUSION: In this EAP, daratumumab monotherapy in Brazilian patients showed a safety and efficacy profile consistent with clinical studies of daratumumab monotherapy in patients with heavily pretreated RRMM. ClinicalTrials.gov identifier: NCT02477891.