Cancers, Vol. 12, Pages 265: Proteasome Inhibitors for the Treatment of Multiple Myeloma
Cancers, Vol. 12, Pages 265: Proteasome Inhibitors for the Treatment of Multiple Myeloma Cancers doi: 10.3390/cancers12020265 Authors: Ito Use of proteasome inhibitors (PIs) has been the therapeutic backbone of myeloma treatment over the past decade. Many PIs are being developed and evaluated in the preclinical and clinical setting. The first-in-class PI, bortezomib, was approved by the US food and drug administration in 2003. Carfilzomib is a next-generation PI, which selectively and irreversibly inhibits proteasome enzymatic activities in a dose-dependent manner. Ixazomib was the first oral PI to be developed and has a robust efficacy and favorable safety profile in patients with multiple myeloma. These PIs, together with other agents, including alkylators, immunomodulatory drugs, and monoclonal antibodies, have been incorporated into several regimens. This review summarizes the biological effects and the results of clinical trials investigating PI-based combination regimens and novel investigational inhibitors and discusses the future perspective in the treatment of multiple myeloma.
RARITAN, NJ, February 10, 2020 – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval of DARZALEX® (daratumumab) in combination with Kyprolis® (carfilzomib) and dexamethasone (DKd) for relapsed/refractory multiple myeloma. The sBLA is supported by results from the Phase 3 CANDOR study, which compared treatment with DKd to carfilzomib and dexamethasone (Kd) in patients with multiple myeloma who relapsed after one to three prior lines of therapy. “Wh...
CONCLUSIONS: This study provides the basis for studying the addition of JAK inhibitors to improve the efficacy of immunomodulatory agents with steroids for treating myeloma patients but perhaps can also be expanded for treating other cancer patients that are refractory to this class of drugs. PMID: 31937615 [PubMed - as supplied by publisher]
erpos Thromboembolism in multiple myeloma (MM) patients remains a common complication that renders the optimization of our thromboprophylaxis practice necessary. This review aims to make clear the need for the development of more accurate risk assessment tools and means of thrombosis prevention. Current clinical practice is guided by available guidelines published by the IMWG in 2014, but the extent to which these are implemented is unclear. Recently, several groups developed clinical scores for thrombosis risk in MM in an attempt to improve risk stratification, but these have not been validated or used in clinical pra...
Bisphosphonates are increasingly used to treat many conditions including osteoporosis, bony cancer metastases, and multiple myeloma.1 Although generally safe, bisphosphonates carry a small risk of osteonecrosis of the jaw (ONJ).2 ONJ results in exposed necrotic bone in the jaw and may require surgical treatment. Given the rise of bisphosphonate use over the past decade,3 we aimed to evaluate 1) the change in the incidence of ONJ , 2) trends in the surgical treatment of ONJ, and 3) patient-level predictors of surgical treatment.
ConclusionsMaxillofacial manifestation of bone metastasis is common but is often overlooked. Therefore, it should be considered in the differential diagnosis when a patient with a history of antiresorptive medications presents with a gingival mass and/or exophytic bone. Good clinical judgment and well-timed bone biopsy and diagnostic imaging can lead to the correct diagnosis and optimal treatment.
The 8 cases selected for this presentation include medication-related osteonecrosis of the jaw (MRONJ) treated conservatively: 2 cases of breast cancer metastasis, 3 cases of multiple myeloma, and 3 cases of osteoporosis. Two of them occurred in the implant area and in 1 case, the treatment was concluded with hyperbaric oxygen therapy. In 5 cases, a bisphosphonate was given via intravenous route and 3 cases by oral administration. Only 1 case had a combination of bisphosphonates and monoclonal antibody (denosumab).
Bisphosphonates, such as zoledronic acid, are commonly used to treat bone metastasis from malignant conditions, such as multiple myeloma, or from solid tumors, such as breast or prostate cancer. Medication-related osteonecrosis of the jaw (MRONJ) is one of the complications of bisphosphonate treatment. The reported incidence of MRONJ among patients with cancers and bone metastases treated with zoledronic acid is 1.3%. MRONJ has been reported to have an incidence rate of up to 18.5%. The clinical and radiographic presentations of MRONJ are very similar to those of bone metastases, making early diagnosis and timely treatment challenging.
CONCLUSIONS: Although our meta-analysis showed statistically significant increased risks of either cancer incidence or mortality of certain cancers in association with firefighting, a number of important limitations of the underlying studies exist, which, precluded our ability to arrive at definitive conclusions regarding causation. PMID: 31759344 [PubMed - in process]
Condition: Multiple Myeloma Interventions: Drug: Daratumumab Injection; Drug: Dexamethasone Oral; Drug: Lenalidomide Pill; Drug: Bortezomib Injection Sponsors: H. Lee Moffitt Cancer Center and Research Institute; Janssen Scientific Affairs, LLC Recruiting