Efficacy and safety of single-agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-3): a phase 3, open-label, randomised study.

BACKGROUND: Multiple myeloma remains incurable, and heavily pretreated patients with relapsed or refractory disease have few good treatment options. Belantamab mafodotin showed promising results in a phase 2 study of patients with relapsed or refractory multiple myeloma at second or later relapse and a manageable adverse event profile. We aimed to assess the safety and efficacy of belantamab mafodotin in a phase 3 setting. METHODS: In the DREAMM-3 open-label phase 3 study, conducted at 108 sites across 18 countries, adult patients were enrolled who had confirmed multiple myeloma (International Myeloma Working Group criteria), ECOG performance status of 0-2, had received two or more previous lines of therapy, including two or more consecutive cycles of both lenalidomide and a proteasome inhibitor, and progressed on, or within, 60 days of completion of the previous treatment. Participants were randomly allocated using a central interactive response technology system (2:1) to receive belantamab mafodotin 2·5 mg/kg intravenously every 21 days, or oral pomalidomide 4·0 mg daily (days 1-21) and dexamethasone 40·0 mg (20·0 mg if >75 years) weekly in a 28-day cycle. Randomisation was stratified by previous anti-CD38 therapy, International Staging System stage, and number of previous therapies. The primary endpoint was progression-free survival in all patients who were randomly allocated. The safety population included all randomly allocated patients who received one or more doses of study treatment. This trial is registered with ClinicalTrials.gov, NCT04162210, and is ongoing. Data cutoff for this analysis was Sept 12, 2022. FINDINGS: Patients were recruited between April 2, 2020, and April 18, 2022. As of September, 2022, 325 patients were randomly allocated (218 to the belantamab mafodotin group and 107 to the pomalidomide-dexamethasone group); 184 (57%) of 325 were male and 141 (43%) of 325 were female, 246 (78%) of 316 were White. Median age was 68 years (IQR 60-74). Median follow-up was 11·5 months (5·5-17·6) for belantamab mafodotin and 10·8 months (5·6-17·1) for pomalidomide-dexamethasone. Median progression-free survival was 11·2 months (95% CI 6·4-14·5) for belantamab mafodotin and 7·0 months (4·6-10·6) for pomalidomide-dexamethasone (hazard ratio 1·03 [0·72-1·47]; p=0·56). Most common grade 3-4 adverse events were thrombocytopenia (49 [23%] of 217) and anaemia (35 [16%]) for belantamab mafodotin, and neutropenia (34 [33%] of 102) and anaemia (18[18%]) for pomalidomide-dexamethasone. Serious adverse events occurred in 94 (43%) of 217 and 40 (39%) of 102 patients, respectively. There were no treatment-related deaths in the belantamab mafodotin group and one (1%) in the pomalidomide-dexamethasone group due to sepsis. INTERPRETATION: Belantamab mafodotin was not associated with statistically improved progression-free survival compared with standard-of-care, but there were no new safety signals associated with its use. Belantamab mafodotin is being tested in combination regimens for relapsed or refractory multiple myeloma. FUNDING: GSK (study number 207495).

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.

Application of EBMT, MASCC, and qSOFA Scores to Predict Complicated Febrile Neutropenia and Mortality in Autologous Stem Cell Transplant Recipients.

BACKGROUND AND OBJECTIVES: Three different scores were addressed as predictors of outcomes in autologous stem cell transplant (Auto SCT): one was calculated by pretransplant characteristics (European Society for Blood and Marrow Transplantation [EBMT] risk score), and two were calculated at the onset of febrile neutropenia (Multinational Association for Supportive Care in Cancer [MASCC] and Quick Sequential Organ Failure Assessment [qSOFA]). We considered bloodstream infection (BSI), carbapenem prescription, admission to the intensive care unit (ICU), and mortality as outcomes. PATIENTS: A total of 309 patients with a median age of 54 years were enrolled. RESULTS: Patients with EBMT score ≥4 (EBMT 4+) had higher ICU rates (14% vs. 4%; p < 0.01) and more carbapenem prescriptions (61% vs. 38%; p < 0.001) than those with EBMT score <4. MASCC <21 points (MASCC HR) was associated with carbapenem prescription (59% vs. 44%; p = 0.013), ICU (19% vs. 3%; p < 0.01), and death (4% vs. 0; p = 0.014). Patients with at least two points by qSOFA (qSOFA 2+) had more frequent BSI (55% vs. 22%; p = 0.03), ICU admissions (73% vs. 7; p < 0.01), and death (18% vs. 0.7, p = 0.02). EBMT 4+ and MASCC HR achieved the best sensitivities for ICU. For death, the best sensitivity was obtained with MASCC. CONCLUSION: In conclusion, risk scores for Auto SCT showed an association with outcomes and had different performances when combined or used alone. Therefore, risk scores for Auto SCT are useful in supportive care and clinical surveillance in stem cell transplant recipients.

Adipose Tissue-Derived Stromal/Stem Cells Transplantation with Cholecalciferol Supplementation in Recent-Onset Type 1 Diabetes Patients: Twelve Months Follow-Up.

To evaluate safety and therapeutic effect along 12 months of allogenic adipose tissue-derived stromal/stem cells (ASCs) transplantation with cholecalciferol (VITD) in patients with recent-onset type 1 diabetes (T1D). Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1xKgx106 cells) and VITD 2000UI/day for 12 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide area under the curve (CPAUC), insulin dose, HbA1c and frequency of FoxP3+ in CD4+ or CD8+ T-cells(flow cytometry) were evaluated at baseline(T0), after 3(T3), 6(T6) and 12 months(T12). Eleven patients completed follow up (7:group 1;4:group 2). Group 1 had lower insulin requirement at T3(0.24±0.18vs0.53±0.23UI/kg,p=0.04), T6(0.24±0.15vs0.66±0.33 UI/kg,p=0.04) and T12(0.39±0.15vs0.74±0.29 UI/Kg,p=0.04).HbA1c was lower at T6 (50.57±8.56vs72.25±10.34 mmol/mol,p=0.01), without differences at T12 (57.14±11.98 in group 1 vs. 73.5±14.57 mmol/min in group 2, p=0.16). CPAUC was not significantly different between groups at T0(p=0.07), higher in group 1 at T3(p=0.04) and T6(p=0.006), but similar at T12(p=0.23). IDAA1c was significantly lower in group 1 than group 2 at T3,T6 and T12 (p=0.006, 0.006 and 0.042, respectively). IDDA1c was inversely correlated to FoxP3 expression in CD4 and CD8+ T cells at T6 (p<0.001 and p=0.01, respectively). In group 1, one patient had recurrence of a benign teratoma that was surgically removed, not associated to the intervention. ASCs with VITD without immunosuppression were safe and associated lower insulin requirements, better glycemic control, and transient better pancreatic function in recent onset T1D, but the potential benefits were not sustained.

Lenalidomide Maintenance and Measurable Residual Disease in a Real-World Multiple Myeloma Transplanted Population Receiving Different Treatment Strategies Guided by Access to Novel Drugs in Brazil.

Despite recent advances in multiple myeloma (MM), the incorporation of novel agents and measurable residual disease (MRD) monitoring in low-income countries remains a challenge. Although lenalidomide maintenance (M-Len) after autologous stem cell transplantation (ASCT) has been associated with improved outcomes and MRD has refined the prognosis of complete response (CR) cases, until now, there have been no data on the benefits of these approaches in Latin America. Here, we evaluate the benefits of M-Len and MRD using next-generation flow cytometry (NGF-MRD) at Day + 100 post-ASCT (n = 53). After ASCT, responses were evaluated based on the International Myeloma Working Group criteria and NGF-MRD. MRD was positive in 60% of patients with a median progression-free survival (PFS) of 31 months vs. not reached (NR) for MRD-negative cases (p = 0.05). The patients who received M-Len continuously had a significantly better PFS and overall survival (OS) than those without M-Len (median PFS: NR vs. 29 months, p = 0.007), with progression in 11% vs. 54% of cases after a median follow-up of 34 months, respectively. In a multivariate analysis, MRD status and M-Len therapy emerged as independent predictors of PFS (median PFS of M-Len/MRD- vs. no M-Len/MRD+ of NR vs. 35 months, respectively; p = 0.01). In summary, M-Len was associated with improved survival outcomes in our real-world MM cohort in Brazil, with MRD emerging as a useful reproducible tool to identify patients at an earlier risk of relapse. The inequity in drug access remains a hurdle in countries with financial constraints, with a negative impact on MM survival.

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.

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.

Incorporation of medicines in the Unified Health System (SUS): comparison between oncology and the specialized component of pharmaceutical care. / Incorporação de medicamentos no SUS: comparação entre oncologia e componente especializado da assistência farmacêutica.

Compliance with legal deadlines for the assessment and incorporation of technologies in Brazil's Unified Health System (SUS) is essential to ensure public access to essential medicines. The scope of this paper was to analyze the compliance with legal deadlines for incorporation and availability of medicines in the SUS, comparing Oncology and the Specialized Component of Pharmaceutical Assistance (SCPA). A comparison was made of the drugs incorporated that were submitted to Conitec in the period from January 1, 2017, to April 30, 2020. A total of 85 drugs were recommended for incorporation by Conitec, of which 15 (17.64%) were for Oncology and 70 (82.36%) were for SCPA. The time between analysis and recommendation by Conitec until the publication of the decision by the Ministry of Health was, on average, 86 days longer for oncological drugs and the availability timeframe of technologies incorporated in the oncology area was, on average, 389 days longer than for SCPA. The major progress achieved with the creation of Conitec in Brazil is acknowledged, but the results of this study point to a pressing need to improve the process of making available technologies incorporated into the SUS, especially in oncology.

O cumprimento dos prazos legais para incorporação e disponibilização de tecnologias no Sistema Único de Saúde (SUS) é fundamental para o acesso da população aos medicamentos considerados essenciais. Objetivou-se analisar o cumprimento destes prazos comparando a Oncologia e o Componente Especializado de Assistência Farmacêutica (CEAF). Comparou-se os processos de incorporação de medicamentos no SUS da Oncologia e do CEAF que foram submetidos à Conitec no período de 01 de janeiro de 2017 a 30 de abril de 2020. No período, 83 processos de incorporação de medicamentos foram recomendados para incorporação pela Conitec, dos quais 13 (15,66%) eram da Oncologia e 70 (84,34%) eram do CEAF. Verifica-se que o tempo de análise e recomendação pela Conitec até a publicação da decisão pelo Ministério da Saúde foi, em média, 15 dias maior para processos que continham medicamentos oncológicos e o tempo para disponibilização das tecnologias incorporadas da área da oncologia foi, em média, 389 dias maior que do CEAF. Reconhece-se o importante avanço obtido com a criação da Conitec no Brasil, porém os resultados deste estudo apontam para a necessidade de aprimoramento do processo de disponibilização de tecnologias incorporadas no SUS, em especial da Oncologia.

Incorporação de medicamentos no SUS: comparação entre oncologia e componente especializado da assistência farmacêutica / Incorporation of medicines in the Unified Health System (SUS): comparison between oncology and the specialized component of pharmaceutical care

Resumo O cumprimento dos prazos legais para incorporação e disponibilização de tecnologias no Sistema Único de Saúde (SUS) é fundamental para o acesso da população aos medicamentos considerados essenciais. Objetivou-se analisar o cumprimento destes prazos comparando a Oncologia e o Componente Especializado de Assistência Farmacêutica (CEAF). Comparou-se os processos de incorporação de medicamentos no SUS da Oncologia e do CEAF que foram submetidos à Conitec no período de 01 de janeiro de 2017 a 30 de abril de 2020. No período, 83 processos de incorporação de medicamentos foram recomendados para incorporação pela Conitec, dos quais 13 (15,66%) eram da Oncologia e 70 (84,34%) eram do CEAF. Verifica-se que o tempo de análise e recomendação pela Conitec até a publicação da decisão pelo Ministério da Saúde foi, em média, 15 dias maior para processos que continham medicamentos oncológicos e o tempo para disponibilização das tecnologias incorporadas da área da oncologia foi, em média, 389 dias maior que do CEAF. Reconhece-se o importante avanço obtido com a criação da Conitec no Brasil, porém os resultados deste estudo apontam para a necessidade de aprimoramento do processo de disponibilização de tecnologias incorporadas no SUS, em especial da Oncologia.

Abstract Compliance with legal deadlines for the assessment and incorporation of technologies in Brazil's Unified Health System (SUS) is essential to ensure public access to essential medicines. The scope of this paper was to analyze the compliance with legal deadlines for incorporation and availability of medicines in the SUS, comparing Oncology and the Specialized Component of Pharmaceutical Assistance (SCPA). A comparison was made of the drugs incorporated that were submitted to Conitec in the period from January 1, 2017, to April 30, 2020. A total of 85 drugs were recommended for incorporation by Conitec, of which 15 (17.64%) were for Oncology and 70 (82.36%) were for SCPA. The time between analysis and recommendation by Conitec until the publication of the decision by the Ministry of Health was, on average, 86 days longer for oncological drugs and the availability timeframe of technologies incorporated in the oncology area was, on average, 389 days longer than for SCPA. The major progress achieved with the creation of Conitec in Brazil is acknowledged, but the results of this study point to a pressing need to improve the process of making available technologies incorporated into the SUS, especially in oncology.

Blinatumomabe em pacientes pediátricos com leucemia linfoblástica aguda B em primeira recidiva de alto risco: um estudo de custo-efetividade / Blinatumomab in high-risk first relapse pediatric patients with acute lymphoblastic leukemia: a cost-effectiveness analysis

Objetivo: Estimar a custo-efetividade do blinatumomabe como novo padrão no tratamento de consolidação de pacientes pediátricos com leucemia linfoblástica aguda de células precursoras B (LLA-B) em primeira recidiva de alto risco. Métodos: Um modelo de sobrevida particionado com horizonte lifetime e ciclo de quatro semanas foi construído na perspectiva do Sistema Único de Saúde (SUS). Sobrevida livre de eventos e sobrevida global foram extrapoladas com base no ensaio clínico 20120215, usando funções paramétricas. A taxa de desconto foi de 5%. O impacto de variações em pressupostos foi explorado em análises de cenário. Resultados: O custo lifetime com desconto para o caso base foi de R$ 351.615 para blinatumomabe contra R$ 97.770 para HC3 (grupo controle de quimioterapia-padrão), com ganho de 9,96 e 6,74 anos de vida ajustados para qualidade (QALYs), respectivamente. A razão de custo-efetividade incremental (RCEI) foi de R$ 78.873/QALY. Considerando um cenário sem descontos, a RCEI foi de R$ 33.731/QALY ganho. Os outros cenários com maior impacto na RCEI foram a exclusão do desperdício de blinatumomabe (isto é, considerando que a sobra em frasco-ampola de um paciente seria reaproveitada para outro paciente: R$ 35.751) e a alteração do tempo de infusão (troca de bolsa em 48 ou 96 horas em vez de 24 horas: R$ 35.515). A probabilidade de o blinatumomabe ser custo-efetivo foi de 65,7% na análise probabilística, considerando um limiar de R$ 95.501. Conclusões: Blinatumomabe é custo-efetivo para pacientes pediátricos com LLA-B derivada em primeira recidiva de alto risco na perspectiva do SUS.

Objective: To estimate the cost-effectiveness of blinatumomab as the new standard treatment of consolidation in high-risk first relapse pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL). Methods: A partitioned survival model with a lifetime horizon and a 4-week cycle was developed from the Brazilian public healthcare payer's perspective (SUS). Event-free survival and overall survival were extrapolated based on data from the 20120215 clinical trial using parametric functions. A 5% discount rate was used, and the impact of variations in model parameters and assumptions were explored in scenario analyses. Results: The discounted base case lifetime cost was R$ 351,615 for blinatumomab vs. R$ 97,770 for standard chemotherapy control group (HC3), with 9.96 QALYs gained with blinatumomab vs. 6.74 QALYs gained with HC3. The incremental costeffectiveness ratio (ICER) was R$ 78,873/QALY. Considering an undiscounted scenario, the ICER was.

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.

Adipose tissue-derived stromal/stem cells + cholecalciferol: a pilot study in recent-onset type 1 diabetes patients

ABSTRACT Objective: Adipose tissue-derived stromal/stem cells (ASCs) and vitamin D have immunomodulatory actions that could be useful for type 1 diabetes (T1D). We aimed in this study to investigate the safety and efficacy of ASCs + daily cholecalciferol (VIT D) for 6 months in patients with recent-onset T1D. Materials and methods: In this prospective, dual-center, open trial, patients with recent onset T1D received one dose of allogenic ASC (1 x 106 cells/kg) and cholecalciferol 2,000 UI/day for 6 months (group 1). They were compared to patients who received chol-ecalciferol (group 2) and standard treatment (group 3). Adverse events were recorded; C-peptide (CP), insulin dose and HbA1c were measured at baseline (T0), after 3 (T3) and 6 months (T6). Results: In group 1 (n = 7), adverse events included transient headache (all), mild local reactions (all), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), scotomas (n = 2), and central retinal vein occlusion at T3 (n = 1, resolution at T6). Group 1 had an increase in basal CP (p = 0.018; mean: 40.41+/-40.79 %), without changes in stimulated CP after mixed meal (p = 0.62), from T0 to T6. Basal CP remained stable in groups 2 and 3 (p = 0.58 and p = 0.116, respectively). Group 1 had small insulin requirements (0.31+/- 0.26 UI/kg) without changes at T6 (p = 0.44) and HbA1c decline (p = 0.01). At T6, all patients (100%; n = 7) in group 1 were in honeymoon vs 75% (n = 3/4) and 50% (n = 3/6) in groups 2 and 3, p = 0.01. Conclusions: Allogenic ASC + VIT D without immunosuppression was safe and might have a role in the preservation of β-cells in patients with recent-onset T1D. ClinicalTrials.gov: NCT03920397.

Adipose tissue-derived stromal/stem cells + cholecalciferol: a pilot study in recent-onset type 1 diabetes patients.

OBJECTIVE: Adipose tissue-derived stromal/stem cells (ASCs) and vitamin D have immunomodulatory actions that could be useful for type 1 diabetes (T1D). We aimed in this study to investigate the safety and efficacy of ASCs + daily cholecalciferol (VIT D) for 6 months in patients with recent-onset T1D. METHODS: In this prospective, dual-center, open trial, patients with recent onset T1D received one dose of allogenic ASC (1 × 106 cells/kg) and cholecalciferol 2,000 UI/day for 6 months (group 1). They were compared to patients who received chol-ecalciferol (group 2) and standard treatment (group 3). Adverse events were recorded; C-peptide (CP), insulin dose and HbA1c were measured at baseline (T0), after 3 (T3) and 6 months (T6). RESULTS: In group 1 (n = 7), adverse events included transient headache (all), mild local reactions (all), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), scotomas (n = 2), and central retinal vein occlusion at T3 (n = 1, resolution at T6). Group 1 had an increase in basal CP (p = 0.018; mean: 40.41+/-40.79 %), without changes in stimulated CP after mixed meal (p = 0.62), from T0 to T6. Basal CP remained stable in groups 2 and 3 (p = 0.58 and p = 0.116, respectively). Group 1 had small insulin requirements (0.31+/- 0.26 UI/kg) without changes at T6 (p = 0.44) and HbA1c decline (p = 0.01). At T6, all patients (100%; n = 7) in group 1 were in honeymoon vs 75% (n = 3/4) and 50% (n = 3/6) in groups 2 and 3, p = 0.01. CONCLUSION: Allogenic ASC + VIT D without immunosuppression was safe and might have a role in the preservation of ß-cells in patients with recent-onset T1D. ClinicalTrials.gov: NCT03920397.