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Rinsho Ketsueki ; 60(9): 1243-1256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31597850


Multiple myeloma is a malignant plasma cell neoplasm that is incurable despite significant progress in treatment over the past several decades. The incorporation of novel agents and combinations into the MM treatment paradigm has resulted in improved survival and tolerability, as well as deeper responses including achieving a minimal residual disease negative state. The addition of new treatment options and combinations has added complexity in treatment selection for myeloma patients. The current strategy for newly diagnosed myeloma involves induction, consolidation, and maintenance therapy. However, nearly all myeloma patients will develop refractory disease. This highlights the need for more effective therapies targeting the myeloma cells and their microenvironment. In this article, we summarize current management of transplant eligible and ineligible newly diagnosed patients in both the upfront and relapsed refractory setting, highlighting risk adapted strategies. We also summarize emerging therapies, such as immune and targeted approaches, as well as drugs with novel mechanisms of action. Emerging strategies offer individualized treatment options and may ultimately offer the possibility of a cure for myeloma patients.

Mieloma Múltiplo/terapia , Gerenciamento Clínico , Humanos , Imunoterapia , Terapia de Alvo Molecular , Microambiente Tumoral
J Oncol Pharm Pract ; 25(6): 1402-1411, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30782080


PURPOSE: We evaluated if the development of thyroiditis in patients who received treatment with immune checkpoint inhibitors across various tumor types was associated with tumor response. METHODS: In this retrospective, single-center, cross-sectional study, patients with various tumor types who received treatment with nivolumab or pembrolizumab as standard of care were evaluated. The primary endpoint was to evaluate the objective response rate in patients who developed thyroiditis compared with patients who did not develop thyroiditis. Secondary endpoints included disease control rate, progression-free survival, and overall survival. RESULTS: One hundred and three patients were included for analysis with a median follow-up duration of 12.8 months (range, 4.0-21.6). The data cutoff was 31 December 2016. The objective response rate was 38.2% among the 34 patients in the thyroiditis group and 17.4% in the 69 patients in the non-thyroiditis group (p = 0.028). Progression-free survival was longer in the thyroiditis group than in the non-thyroiditis group. The median progression-free survival was 10.1 months (95% CI, 1.6-18.5) in the thyroiditis group and 3.7 months (95% CI, 2.5-4.9) in the non-thyroiditis group (hazard ratio, 0.45; 95% CI, 0.27-0.76; p = 0.002). CONCLUSION: Patients with various tumor types who received treatment with immune checkpoint inhibitors and developed thyroiditis had a higher objective response rate than those who did not develop thyroiditis. The development of thyroiditis should be investigated further in the context of prospective randomized trials as a surrogate marker for tumor response to treatment with immune checkpoint inhibitor therapies.

J Oncol Pharm Pract ; 25(8): 1860-1866, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30636529


PURPOSE: Urinary alkalinization with intravenous sodium bicarbonate is standard during high-dose methotrexate administration. Due to a national intravenous sodium bicarbonate shortage, a urinary alkalinization protocol involving hyperhydration with intravenous fluids, oral bicarbonate, and intravenous or oral acetazolamide was utilized from 10 April to 30 May 2017 ("shortage protocol"). This study compared outcomes between protocols. METHODS: A single-center, retrospective chart review was conducted for adults who received methotrexate ≥500 mg/m2 on ≥ two occasions, at least once during each protocol, between 19 February and 19 July 2017. RESULTS: Eighteen patients (50% male), median age 65 years, received 76 total high-dose methotrexate cycles. Shortage protocol was used in 37 cycles (48.7%). Mean time to methotrexate clearance did not differ between groups (p = ns). Mean time to urinary alkalinization and duration of hospitalization were not statistically different (p = 0.49 and 0.23, respectively). Average total bicarbonate administered per 24 hours was higher in standard protocol (p < 0.05), but hydration rates were similar (p = 0.73). Creatinine clearance and urine output on days 1 and 2 post-high-dose methotrexate did not significantly differ (creatinine clearance day 1, p = 0.27; creatinine clearance day 2, p = 0.55; urine output day 1, p = 0.62; urine output day 2, p = 0.60). Interruptions in alkalinization were significantly higher during shortage (0.41 ± 0.75 instances of urine pH < 7 during standard vs. 1.3 ± 1.7 under shortage, p < 0.05).