Background Granulocyte-colony-stimulating factor (GM-CSF) is a pleiotropic factor for hematopoiesis that stimulates myeloblasts, monoblasts and mobilization of bone marrow stem cells. Therefore, the GM-CSF gene is a potential candidate for vessel formation and tissue remodeling in the treatment of ischemic diseases.
Limited data are available regarding contemporary multiple myeloma (MM) treatment practices in Latin America. In this retrospective cohort study, medical records were reviewed for a multinational cohort of 1103 Latin American MM patients (median age, 61 years) diagnosed in 2008-2015 who initiated first-line therapy (LOT1). Of these patients, 33Á9% underwent autologous stem cell transplantation (ASCT). During follow-up, 501 (45Á4%) and 129 (11Á7%) patients initiated second-(LOT2) and thirdline therapy (LOT3), respectively. In the LOT1 setting, from 2008 to 2015, there was a decrease in the use of thalidomide-based therapy, from 66Á7% to 42Á6%, and chemotherapy from, 20Á2% to 5Á9%, whereas use of bortezomib-based therapy or bortezomib + thalidomide increased from 10Á7% to 45Á5%. Bortezomib-based therapy and bortezomib + thalidomide were more commonly used in ASCT patients and in private clinics. In non-ASCT and ASCT patients, median progression-free survival (PFS) was 15Á0 and 31Á1 months following LOT1 and 10Á9 and 9Á5 months following LOT2, respectively. PFS was generally longer in patients treated with bortezomib-based or thalidomide-based therapy versus chemotherapy. These data shed light on recent trends in the management of MM in Latin America. Slower uptake of newer therapies in public clinics and poor PFS among patients with relapsed MM point to areas of unmet therapeutic need in Latin America.
235 Background: AAP is approved for patients with chemotherapy-naïve mCRPC, but the population with previous use of DES was not studied before. DES is a commonly used hormone therapy for mCRPC in second and plus lines, especially in developing countries, due to lack of access to novel and efficacious therapies. The objective of this trial is to describe the efficacy and safety of AAP after DES treatment in patients who are chemotherapy-naïve, potentially affecting chemotherapy onset. This is the first and only prospective trial to show this data. Methods: This phase 2 multicenter, open-label single-arm study evaluated 46 patients receiving AA (1000 mg daily) + low-dose prednisone (P; 10 mg daily) and androgen deprivation therapy in patients with DES–refractory mCRPC enrolled from Oct 2014 to Oct 2015. The primary efficacy endpoint was time to prostate-specific antigen progression (PSAP) by Prostate Cancer Working Group (PCWG2) criteria. Secondary endpoints included PSA response (≥50% reduction), overall survival, and safety. Results: At baseline, median age was 69 years, median PSA was 40 ng/mL, there were no visceral metastases, 98% of patients had Eastern Cooperative Oncology Group Performance Status 0-1, and 44% had Gleason scores ≥7. Thirty two subjects (71.1%) had PSAP. PSA response was achieved by 47% of patients at week 12 and 56% at any time. Three patients remain on study drug and 4 are in follow-up. AA treatment continued until PSAP, clinical progression, consent withdrawal, or unacceptable toxicity. The median duration of study treatment was 8.6 months. The median time to PSAP was 7.4 months (95% CI = 5.6-9.4) and the median overall survival was 25.6 months (95% CI = 15.7-NE). Treatment-related adverse events included hypertension (19.6%), hyperglycemia (19.6%), fatigue (17.4%), and hypokalemia (4.5%); most grade 1-2. Conclusions: The present study confirmed that AAP provides PSA responses even in heavily treated patients, showing clinical benefit post-DES in chemotherapy-naive mCRPC patients. It also confirmed tolerability of AAP, with an easily manageable toxicity profile. Clinical trial information: NCT02217566.
Background:Treatment options for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) are limited. Ibrutinib is a first-in-class small-molecule inhibitor of Bruton's tyrosine kinase. These extended access programs (EAP) provided patient access to ibrutinib in Brazil and real-world safety data was collected, at a time when the medication was not commercially available in Brazil. Methods:These two prospective, multicenter, open-label EAPs of single-agent ibrutinib were conducted between April 2013 and August 2017, and enrolled Brazilian patients with relapsed/refractory CLL or MCL. Eligible patients must have progressive disease after at least one prior therapy and not suitable for retreatment with purine analogue therapy. After a 30-day screening, eligible patients received once-daily oral ibrutinib 420 mg (CLL) or 560 mg (MCL) continuously until disease progression, unacceptable toxicity, absence of clinical benefit, or end of EAP, whichever occurred first. Doses could be withheld or reduced based on toxicity. Patients were monitored for safety and disease evaluations were conducted per routine local standard of care practices. Results:Of 33 CLL patients enrolled, 32 received one dose of drug or more and were included in the safety analysis. Median age was 62.5 years, and most patients were male (n=24; 75%) and white (n=27; 84.4%). The median time from CLL diagnosis to study inclusion was 83.8 months and from diagnosis to relapsed/refractory state, 42.0 months. The median number of ibrutinib cycles was 12.0 (1.0-16.0) with a median treatment duration of 11.1 (0.9-11.6) months. Eight patients discontinued due to adverse event (AE; n = 4; 12.5%), consent withdrawal (n = 2; 6.3%), death (n = 1; 3.1%), or disease progression (n = 1; 3.1%). AEs leading to treatment discontinuation were intestinal bleeding, neutropenia, infection, and gastric tumor (one patient each). Three (9.4%) patients had dose reductions: one (3.1%) for neutropenia, febrile neutropenia with pneumonia, or worsening fatigue. 21 patients (65.6%) had at least one Grade ≥3 (G3) AE or serious AE (SAE). The most frequent G3 or SAEs included neutropenia in 8 (25.0%), fatigue (1), leukocytosis (1), and pneumonia (3). No atrial fibrillation or bleeding AEs were reported. Among the 47 G3 or SAEs, 17 (36.2%) were serious, 38 (80.9%) were suspected to be related to ibrutinib, and 39 (83.0%) were resolved without sequelae. All 13 MCL patients enrolled in the study were included in the safety analysis. The median age was 60.0 years, and most patients were male (n=9; 69.2%) and white (n=9; 69.2%). The median number of prior treatment regimens were 3. The median time from diagnosis to the first dose of ibrutinib was 20.4 months. The median number of ibrutinib cycles was 19 (4.0-34.0) with a median treatment duration of 16.8 (3.6-30.5) months. Eight patients discontinued because of either death (n=3; 23.1%) or disease progression (n=5; 38.5%). The three patients died with treatment-emergent G4 or higher AEs, including pneumonia (G5; probably treatment-related [TR]), sepsis (G5; not TR), and dyspnea (G4; doubtful TR); 8 patients (61.5%) had at least one G3 or higher treatment-emergent AE. The most frequent AE was diarrhea (n=3; 23.1%), and other AEs were reported in one patient each (i.e. abdominal hernia, anemia, appendicitis, dyspnea, febrile neutropenia, influenza, leukocytosis, neutropenia, pneumonia, productive cough, renal failure/insufficiency, retroperitoneal abscess, thrombocytopenia). Three (23.1%) patients had ibrutinib dose modifications: one (7.7%) each because of appendicitis/tuberculosis, thrombocytopenia, and diarrhea/retroperitoneal abscess/dyspnea. No atrial fibrillation or bleeding AEs were reported. Among the 20 G3 or higher treatment-emergent AEs, 14 (70%) were suspected to be related to ibrutinib and 15 (75%) were resolved. Conclusions: This is the first real-world experience with ibrutinib monotherapy for CLL and MCL in Brazil. Overall, treatment was well tolerated with no unexpected toxicities. No atrial fibrillation or bleeding AEs were reported. Of 32 patients with relapsed/refractory CLL, 24 (80%) remained on therapy, 4 (12.5%) discontinued due to AEs, 1 (3.1%) each died or experienced disease progression. Among 13 patients with relapsed/refractory MCL, 5 (38.5%) remained on the therapy, 3 (23.1%) died and 5 (38.5%) experienced disease progression. Disclosures Chiattone: Janssen: Honoraria, Research Funding. Fogliatto:Novartis: Consultancy; Janssen: Honoraria, Research Funding; Roche: Consultancy, Speakers Bureau. Scheinberg:Novartis: Consultancy, Speakers Bureau; Janssen: Honoraria, Research Funding; Pfizer: Speakers Bureau. Bigni:Janssen: Honoraria, Research Funding. Rodrigues:Janssen: Honoraria, Research Funding. Garicochea:Janssen: Honoraria, Research Funding. Pimenta:Janssen: Honoraria, Research Funding. Boechat:Janssen: Honoraria, Research Funding. Musacchio:Janssen: Honoraria, Research Funding. Goncalves:Janssen: Honoraria, Research Funding. Vieira:Janssen: Honoraria, Research Funding. Santos:Janssen: Employment. Grings:Janssen: Employment. Parisi:Janssen: Employment. Barreyro:Janssen: Employment.
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