Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study
Publication date: Available online 14 November 2019Source: The LancetAuthor(s): Michel Attal, Paul G Richardson, S Vincent Rajkumar, Jesus San-Miguel, Meral Beksac, Ivan Spicka, Xavier Leleu, Fredrik Schjesvold, Philippe Moreau, Meletios A Dimopoulos, Jeffrey Shang-Yi Huang, Jiri Minarik, Michele Cavo, H Miles Prince, Sandrine Macé, Kathryn P Corzo, Frank Campana, Solenn Le-Guennec, Franck Dubin, Kenneth C AndersonSummaryBackgroundIsatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma.MethodsWe did a randomised, multicentre, open-label, phase 3 study at 102 hospitals in 24 countries in Europe, North America, and the Asia-Pacific regions. Eligible participants were adult patients with relapsed and refractory multiple myeloma who had received at least two previous lines of treatment, including lenalidomide and a proteasome inhibitor. Patients were excluded if they were refractory to previous treatment with an anti-CD38 monoclonal antibody. We ...
The objective of this single-center, open-label, randomized, phase II study was to evaluate the safety and efficacy of dexamethasone solution (standard of care) in Mucolox (group A) compared with dexamethasone solution alone (group B) for the treatment of OLP. The primary outcome measure was to detect changes in each subject's sensitivity scores (0–10) evaluated at baseline and after 4 weeks of treatment.Study DesignPatients with clinical OLP and a visual analogue scale (VAS) sensitivity score of 7 or greater were randomized to group A or group B. REU (Reticulation/keratosis, erythema, and ulceration) scoring, VAS fo...
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.
ConclusionsThis case demonstrates the simultaneous presentation of multiple conditions. Oral biopsy revealed a solitary focus of granulomatous inflammation, indicative of orofacial granulomatosis. However, the biopsied lesion was also unusual in that inflammation extended into the epithelium, a relatively unusual feature for a granulomatous inflammatory disease and a pattern more commonly seen in vesiculobullous eruptions. Because this patient's CD was well controlled, it is difficult to believe that these oral lesions were associated with CD activity. One reasonable assumption is that the long-time treatment of the patien...
Multiple myeloma (MM) is a neoplastic disorder originating from clonal proliferation of malignant plasma cells in the bone marrow microenvironment. MM is identified by the accumulation of differentiated B cells. The aim of this study is to report a case of a 65-year-old man presenting with a sessile swelling on the left palate measuring 8 cm in its largest diameter and covered by a necrotic membrane on the central surface area. Provisional clinical diagnosis included mucoepidermoid carcinoma and squamous cell carcinoma and an incisional biopsy was performed.
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).
A 54-year-old black female patient undergoing dexamethasone and bortezomib therapy for multiple myeloma presented with asymptomatic papules and nodules on the border of the tongue. The lesions were firm in consistency, with light yellowish color and ranging in size from 0.2 to 0.6 cm. A biopsy was performed, and the histopathologic examination with hematoxylin and eosin showed an extracellular deposition of eosinophilic material within the connective tissue. Congo red stain confirmed the diagnosis of amyloidosis.
A 51-year-old white female patient hospitalized in the intensive care unit because of acute ischemic stroke who needed tracheostomy and vasoactive drugs in high dosage evolved with aspiration pneumonia and septic shock. At 30 days of hospitalization, intraoral examination revealed multiple superficial ulcers on the lips, buccal mucosa, tongue, and mouth floor, circumscribed by erythematous halo and covered by pseudomembrane with severe pain symptomatology and evolution of 15 days. Concomitantly, the patient presented bilateral conjunctivitis with erythema in the sclera and periocular region.
Graft-vs-host disease (GVHD) is the main complication of allogeneic hematopoietic stem cells transplantation. A 29-year-old Brazilian man was diagnosed as having severe aplastic anemia and submitted to allogeneic HSCT in October 2013. He developed systemic chronic GVHD, including the oral cavity (lichenoid lesions in right and left buccal mucosa and labial hyperchromia and was treated with mycophenolate mofetil, tacrolimus, cyclosporine, and dexamethasone solution [mouthwash]). Upon stabilization of chronic GVHD in the oral cavity, the patient displayed gingival atrophy and erythema (12-21/33-42) on July 27, 2017.
A 76-year-old man with medical history of anemia was referred for clinical investigation of hoarseness and dysphagia over the last 2 years. Extraoral head and neck examination revealed diffuse hardened skin. Intraoral examination revealed macroglossia with restricted tongue movement and hardening of the lower lip mucosa. Digital panoramic radiograph revealed discreet radiolucent areas affecting the mandible. Incisional biopsy was performed under local anesthesia on the tongue and lower lip. Histopathologic analysis revealed a deposition of hyaline material, mainly surrounding minor salivary glands.
A 56-year-old woman was referred in April 2016 complaining of "pain in the jaw and body." She reported having several professional opinions, but diagnosis was not determined. On her first appointment, she presented with an orthopantomography and skull radiographs that showed multiple punched-out lesions widespread in the jaw and skull. Under the suspicion of multiple myeloma, laboratory tests and computed tomography were requested, and a biopsy of the mandibular lesion was scheduled. During biopsy, a perforation of the cortex was noticed, and the hypothesis of a malignant lesion was reinforced.