Advertisement
Pembrolizumab Looks Promising in Multiple Myeloma
Tweet this page
Advertisement
Initial efficacy results show promising activity in heavily pretreated patients with relapsed or refractory multiple myeloma and support the continued development of pembrolizumab in these patients.
—Jesus San Miguel, MD
Monoclonal antibodies targeting the programmed cell death protein (PD-1) receptor look promising in multiple myeloma, according to early reports presented at the 2015 ASH Annual Meeting and Exposition. Early signs of activity in heavily pretreated patients may indicate that, as in solid tumors, these immunotherapy agents may be beneficial in at least some hematologic malignancies.
Preliminary findings from the phase I KEYNOTE-023 study of pembrolizumab (Keytruda) were presented by Jesus San Miguel, MD, of the University of Navarra, Pamplona, Spain,1 and Ashraf Z. Badros, MD, of the University of Maryland, Baltimore, presented results of a phase II study combining pembrolizumab with pomalidomide (Pomalyst) and dexamethasone.2 Both trials are continuing to accrual, and final results are expected.
“Initial efficacy results show promising activity in heavily pretreated patients with relapsed or refractory multiple myeloma and support the continued development of pembrolizumab in these patients,” Dr. San Miguel said.
Possible Antitumor Synergy
PD-1 is upregulated on the surface of activated T cells and its ligands (PD-L1 and PD-L2) are expressed on the surface of antigen-presenting cells and tumor cells. Binding of the PD-1 receptor to its ligands inhibits T-cell activation. The PD-1 pathway is often exploited by tumors to evade immune surveillance, Dr. San Miguel explained.
Ashraf Z. Badros, MD
Pembrolizumab is a potent and highly selective humanized anti–PD-1 monoclonal antibody that directly blocks the interaction between PD-1 and its ligands. Pembrolizumab is approved for advanced melanoma and non–small cell lung cancer and has demonstrated robust antitumor activity in multiple cancers.
According to Dr. San Miguel, antitumor synergy is observed when anti–PD-1 antibodies and immunomodulatory drugs are used in combination. “We tested the possibility of combining these two types of treatments that have immune effects, trying to enhance the capacity of the immune system to control tumor cells,” he explained.
KEYNOTE-023 Details
The phase I KEYNOTE-023 trial enrolled 50 patients with relapsed/refractory myeloma who progressed on two or more prior therapies (median of four). The study had a dose determination phase, a dose confirmation phase, and a dose expansion phase.
Dr. San Miguel emphasized the refractory nature of this population, noting that 70% had at lea more than 95% were exposed to both lenalidomide and bortezomib (Velcade) and 25% were exposed to carfilzomib (Kyprolis) 80% had undergone autolo and 80% were refractory to their last regimen. All 50 patients were evaluable for safety, and 17 from the dose determination and confirmation phases were evaluable for efficacy, a secondary endpoint.
The dose-finding study determined the maximum tolerated dose to be pembrolizumab at 200 mg intravenously every 2 weeks in combination with lenalidomide at 25 mg and low-dose dexamethasone at 40 mg.
High Response Rates
The addition of pembrolizumab to this established myeloma regimen (lenalidomide plus dexamethasone) produced responses in 76% of the 17 evaluable heavily pretreated patients, without excessive toxicity, Dr. San Miguel reported. “If you focus on the nine lenalidomide-refractory patients, five achieved a partial response or better (56%), and three additional patients achieved stable disease,” he added.
The overall disease control rate, indicating response or stable disease for at least 12 weeks, was 88%; only 6% of patients overall and 11% of lenalidomide-refractory patients had progressive disease.
The median duration of response was 9.7 months, and the median time to first response was 1.2 in 11% of patients, response deepened over time. Almost all patients (94%) had a reduction in M protein or free light chains, with 13 of 17 patients experiencing at least a 50% decrease.
The combination was well tolerated, with an adverse-event profile that was consistent with reports of pembrolizumab in solid tumors. Adverse events of any grade were reported by 72% of patients. The most common ≥ grade 3 drug-related events were neutropenia (22%), thrombocytopenia (8%), and anemia (8%). Side effects were consistent with the individual drug safety profiles for the approved indications.
“We did not see any toxicities that were not expected,” said Dr. San Miguel. “We saw both hypothyroid and hyperthyroid adverse events, but we have not seen pneumonitis or colitis so far…. We observed that the safety profile is relatively good, but we are probably underestimating the side effects because the exposure to the drug has been limited. The study is ongoing.” He further cautioned that although the data are “encouraging” they are still preliminary and suggested this combination not be used outside of clinical trials.
Pembrolizumab Plus Pomalidomide and Dexamethasone
Researchers from the University of Maryland combined pembrolizumab with pomalidomide and dexamethasone in a phase II study of 33 relapsed/refractory patients with at least two prior lines of therapy. All patients had abnormal cytogenetics, including 42% with high- 82% were refractory to proteasome inhibitors, 89% were refractory to lenalidomide, and 70% were refractory to both classes of agents.
Patients received pembrolizumab at 200 mg, pomalidomide at 4 mg and dexamethasone at 40 mg. After 24 months, responding patients are being allowed to continue pomalidomide/dexamethasone alone until disease progression.
All 33 patients were assessed for safety, and 27 were ev the median number of cycles was six, and the median follow-up was 7.4 months.
“The regimen shows promising antimyeloma activity and has a predictable and manageable side-effect profile,” Dr. Badros reported.
Pembrolizumab in Myeloma
Pembrolizumab was combined with lenalidomide/dexamethasone in a phase I study of 50 patients and with pomalidomide/dexamethasone in a phase II study of 33 all patients were heavily pretreated.
The response rate was 76% to pembrolizumab/lenalidomide/dexamethasone and 60% to pembrolizumab/pomalidomide/dexamethasone.
Adverse events were consistent with previous studies of the drug in other cancers.
The objective response rate for this regimen was 60% overall, 55% among double-refractory patients, and 50% among patients with high-risk cytogenetics. Only 10% of patients had progressive disease, and 23 of the 27 patients had some reduction in M protein or free light chains. “It’s too early to look at progression-free and overall survival, but the signal we are seeing is quite impressive,” he said. At 6 months, more than 75% of patients appeared progression-free, and approximately 90% were alive.
The researchers are currently working on a means of standardizing the assessment of PD-L1 expression on bone marrow biopsy and exploring methods for determining the impact of fixation and decalcification on the level of expression. ■
Disclosure: Dr. San Miguel is on the advisory board of Millennium, Celgene, Novartis, Onyx, Janssen, BMS, MSD, and Amgen. Dr. Badros reported no potential conflicts of interest.
References
Thierry Facon, MD, of Lille University Hospital in France, spoke to The ASCO Post about the preliminary results of the pembrolizumab studies. Dr. Facon cautioned that a response rate of 76% overall “is not so impressive,” given about 65% of patients respond to lenalidomide/dexamethasone alone....
Advertisement
Advertisement
Today In Oncology
AdvertisementMac上的Powerpoint Keynote for Mac v7.2
苹果软件园官方微信号,求关注:
简介Keynote 拥有各种强大易用的工具与眩目效果，让您轻松制作出令人惊叹精美绝伦的幻灯片！
类似软件推荐
详细介绍iWork三剑客之一的Keynote是一款令人震撼的幻灯片演示文稿，使用无比简单。Keynote 拥有各种强大易用的工具与眩目效果，让您轻松制作出令人惊叹精美绝伦的幻灯片！通过主题选取器，您可快速浏览 44 种 Apple 设计的、给人深刻印象的精选主题。为演示文稿选好完美的画布后，只需将模板占位符处的文本和图形替换为您自己的文字和图像。各种工具简单易用，您可在幻灯片中添加表格、图表、形状、照片和视频，还可选择影院水准的动画和过渡效果，让它看起来栩栩如生，就像由您自己的特效团队打造的一样。注:6.0及以上版本需要Mac OS X 10.9 或更高版本6.5及以上版本需要Mac OS X 10.10 或更高版本
来自Mac App Store官方介绍
Easily create gorgeous presentations with the all-new Keynote, featuring powerful yet easy-to-use tools and dazzling effects that will make you a very hard act to follow. The Theme Chooser lets you skim through an impressive collection of 30 new and updated Apple-designed themes. Once you’ve chosen the perfect canvas for your presentation, simply replace the placeholder text and graphics with your own words and images. Easy-to-use tools let you add tables, charts, shapes, photos, and videos to slides--and bring it all to life with cinematic animations and transitions that look as though they were created by your own special effects team. Animate your data with new interactive column, bar, scatter, and bubble charts. Use iCloud to keep your presentations up to date across all your devices. You can instantly share a presentation using just a link, giving others the latest version and the ability to edit it directly with Keynote for iCloud beta from
using a Mac or PC browser. With Keynote, you have all the tools you need to make an amazing presentation quickly and easily. Get started quickly
Choose from 30 Apple-designed themes to give your presentations a beautiful start Use the slide navigator to quickly skim through your presentation, add new slides, and reorder slides Engage your audience with new interactive charts and chart animations See live on-canvas previews as you animate your slides Use gorgeous preset styles to make your text, tables, shapes, and images look beautiful
Easy-to-use graphics tools
Edit down to the pixel with rulers and alignment guides Simplified toolbar gives you quick access to shapes, media, tables, charts, and sharing options Professional-level graphics tools Use Instant Alpha to easily remove image backgrounds Free-form curves, shapes, and masks Connection lines
Cinema-quality animations
Updated cinematic slide transitions for easily creating stunning presentations Magic Move effect now expanded to animate and morph graphics Gorgeous new slide transitions including Clothesline, Object Cube, Object Flip, and Object Pop New text and object animations including Vanish, Crumble, and Fade and Scale New Emphasis builds let you add impact with one click
Present to your audience
Gorgeous new presenter display with support for up to six displays Recorded narration Create self-running, interactive shows for kiosks and displays Control your slideshow from iPhone, iPad, or iPod touch with the Keynote Remote app (available separately from the App Store for iPhone, iPad, and iPod touch)
Turn on iCloud so you can access and edit your presentations from your Mac, iPad, iPhone, iPod touch,
Access and edit your presentations from a Mac or PC browser at
with Keynote for iCloud beta Keynote automatically saves your presentations as you make changes
Share your work
Use AirDrop to send your presentations to anyone nearby Quickly and easily share a link to your work via Mail, Messages, Twitter, or Facebook Anyone with the link will always have access to the latest version of the presentation and can edit it with you
Take advantage of image and movie size optimization Import a wide range of media types including JPEG, TIFF, PNG, PSD, EPS, PDF, AIFF, MP3, AAC, and MOV Share as Movie to Facebook, Vimeo, and YouTube Export your presentations to Microsoft PowerPoint, PDF, QuickTime, HTML, and image files Choose from many different layouts to print your presentation or create handouts for your audience …更多… v7.2版本新功能
Version 7.2:
Enhance your presentations using a library of over 500 professionally drawn shapes Reply to comments and join threaded conversations New auto-correction and text replacement options save time while typing Scroll anywhere with new pan and zoom options Edit presenter notes while displaying slides in Light Table view Improved support for Hebrew and Arabic languages The Stock and Currency functions now return data from the previous market day’s close. …更多…
相关截图 图片数： 5 张(点击图片查看大图)
上一条：下一条：
下载列表 文件数： 9 文件大小：
& Mac上的Powerpoint Keynote for Mac
苹果软件园官方微信号,专为大家推送苹果相关知识百科,求关注！
小编微信号，有关Mac问题不懂的欢迎扫码咨询,知无不言言无不尽^_^
MAC效率热门APPS