One of the pioneers of CAR T cell therapy in children is Dr Stephan Grupp, who is Director of the Cancer Immunotherapy Program at The Children’s Hospital of Philadelphia (CHOP).
Dr Stephan Grupp ASH16
He led the way in developing ways of treating cytokine release (CRS) syndrome through the use of tocilizumab. At the recent American Society of Hematology annual meeting, Dr Grupp presented the results of the ELIANA study, the first global, multi-center clinical trial with CTL019 (Novartis) in pediatric acute lymphoblastic leukemia (p-ALL).
What was surprising to many at ASH was that despite the fact that CAR T cell therapy is one of the hottest topics in hematology (if not the hottest), many presentations were in small (tiny) meeting rooms, which many people could not get into. Several overflow rooms were rapidly opened up, but still people were left out. Someone clearly did not get the memo!
If you didn’t make into the meeting room at ASH to hear Dr Grupp, he kindly spoke to BSB about the data he presented and also shared his perspective of what the future may hold for CAR T cell therapy in pediatric ALL.
There’s also additional commentary on some of the other key CAR T cell presentations that caught our attention at ASH.
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Over the last five years the face of the chronic lymphocytic leukemia (CLL) landscape has changed quite dramatically with the advent of new approvals in several categories. These include anti-CD20 antibodies, BTK inhibitors, PI3K inhibitors and apoptotic Bcl–2 inhibitors.
In yesterday’s wide ranging interview we explored in-depth how these therapies are impacting the broader landscape, as well as emerging trends in how these regimens might be used.
In Part 2 of the ongoing series, we spoke with another CLL expert and explored promising new and earlier agents in development for a different perspective on how outcomes might be improved further.
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Targeted therapy and Chemo-Immunotherapy in CLL
At last December’s 2016 annual meeting of the American Society of Hematology, one of the areas that attracted attention was the latest clinical data on the treatment of chronic lymphocytic leukemia (CLL).
ASH 2016 in San Diego
In recent years, we’ve seen tremendous advances in the field with several new agents approved such as obintuzumab, ibrutinib, idelalisib, and venetoclax. There are also new treatment options available for CLL patients with high risk disease such as 17p deletions (Del17p).
Other new targeted therapies such as acalabrutinib are now in clinical development, plus we have CAR T cell therapies and combination strategies also being evaluated in the clinic.
So what was the hot news from #ASH16 in CLL?
- Does chemotherapy still have a role or is it a targeted therapy world?
- Are we further forward towards a cure?
- Have we worked out how to identify those at risk of relapse?
- Will CAR T cell therapy be a game changer in CLL?
- Is financial toxicity going to be an issue with combination strategies?
BSB interviewed two experts in CLL while in San Diego who kindly shared their thoughts on which CLL data impressed them at the ASH annual meeting and discussed some of the big strategic issues facing the field right now. These interviews are being posted in a two-part series.
Part 1 today answers some of the questions highlighted above and explores the changing face of the broader CLL landscape.
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One of the interesting and exciting parts of major medical meetings such as the ASH annual meeting, held last month in San Diego, is hearing about new compounds in development.
When it comes to the treatment of aggressive lymphomas, there remains a high unmet medical need to improve the response rate to first line treatment, as well as offer better outcomes post relapse.
At #ASH16, we heard more about a novel ADC called polatuzumab vedotin (Genentech/Roche).
Preliminary safety and clinical data for polatuzumab plus obinituzumab in relapsed or refractory Non-Hodgkin Lymphoma (NHL) was presented in an oral session by Dr Tycel Phillips (University of Michigan).
Three posters were also presented showing early data in combination trials in R/R follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL), as well as in first line DLBCL.
To find out more about the potential of this novel ADC, BSB spoke with Dr Michael Wenger, Senior Group Medical Director at Roche Genentech.
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Yesterday sudden and unexpected news from Seattle Genetics caused quite a stir…
“Seattle Genetics Announces Clinical Hold on Several Phase 1 Trials of Vadastuximab Talirine (SGN-CD33A).”
Part of the Seattle Genetics exhibit booth at #ASH16, taken with permission
In short, over 300 patients have been treated with the ADC and six experienced hepatotoxicity, including several cases of veno-occlusive disease, with four fatalities.
We’ve written about AML several times recently and also received a number of reader questions on this latest development, so it’s time to explore the issue in more depth and look at the implications. We also include some expert commentary from a leukemia specialist for their take on the issue.
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The 2016 annual meeting of the American Society of Hematology with over 27, 000 attendees, a record high, was the venue for the announcement of a major new initiative by the Leukemia Lymphoma Society (LLS), called Beat AML.
It is lead by three well respected researchers in the Hematology/Oncology field:
- Dr John Byrd (Ohio State)
- Dr Brian Druker (OHSU)
- Dr Ross Levine (MSK)
Beat AML is a special project at LLS, who have developed a broad collaboration with academic researchers, pharmaceutical companies, a genomic provider, and a clinical research organization:
Initially, there will be five trial sites, which will each offer all arms of the trial. The centers are:
- Memorial Sloan Kettering Cancer Center in New York
- The Ohio State University Comprehensive Cancer Center in Ohio
- OHSU Knight Cancer Institute in Oregon
- Dana-Farber Cancer Institute and
- Massachusetts General Hospital Cancer Center, both in Massachusetts.
Further sites and (hopefully) also other drugs from pharma companies will be added in due course, so if you’re interested in joining this project, do contact them after checking out more details here!
For our industry readers, this would be a great opportunity to get involved in an exciting and landmark study for AML, whether you are a researcher or a company with a promising drug in early development. These types of trials can help speed up drug development if a therapy graduates in a particular subset.
Here, we offer an in-depth analysis of the scientific and clinical rationale behind this important landmark study and the targets/drugs selected to date.
BSB also spoke with Dr Brian Druker, Director of the Oregon Health and Science University (OHSU) Knight Cancer Institute in Portland, Oregon, who offers additional insights on the special project.
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John P. Leonard, MD is the Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at Weill Cornell in New York. He’s a Lymphoma specialist.
Dr John Leonard at ASH16
Like many hematologists, he’s embraced Twitter as way to share his expertise with others in the hematology community. You can follow him at @JohnPLeonardMD.
Over the last couple of years prior to the ASH annual meeting, Dr Leonard has highlighted 10 lymphoma abstracts that caught his attention. You can tell he gets excellent social media pickup by the fact he’s even generated a hashtag to make them easy to find: #Leonardlist and other hematologists generate conversations around his eagerly awaited picks:
In case you missed them on Twitter, and in the spirit of David Letterman, Dr Leonard took me through this year’s #LeonardList and thoughtfully explained in detail why each selection made the cut… for oncology watchers, the why is often more important than the what.
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Some cancer conferences attract more questions and queries than others.
Old Town San Diego
Interestingly, ASH is always a popular meeting for attendees and readers alike, so it is good to see another batch of critical questions come in so soon after the last one. It’s a while since we did two BSB reader Q&A mailbags from a single meeting!
Not surprisingly, there were also a bunch of questions on CAR T cell therapies, which continue to dominate readers minds, as well as related issues. Here, we answer the most pressing questions that have come in over the last week.
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After regularly reporting here at BSB on several readouts in terms of antibodies and CARs since ASH last year, it’s reasonable to conclude now that there has been growing interest in BCMA–APRIL as a target in multiple myeloma (MM). The CAR T cell therapies have generally focused on BCMA or BCMA-TACI as a target, while antibody approaches such as Aduro’s, BION–1301, target APRIL.
T cells attacking a cancer cell
These new therapies have all been either preclinical in nature or preliminary phase 1 studies in a very limited number of patients, meaning that the best we can characterise them is that old reliable chestnut, ‘promising but early’… to do otherwise would be rather extravagant and hopeful at best.
Given the data from several CAR T cell therapy studies were being presented at two meetings on two separate continents only a few days apart, it makes sense to review them as a whole.
It’s therefore time for a detailed update, including a review of the differences in the key studies, a look at where we are now, as well as tips on what to look for going forward.
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San Diego – Monday at the 2016 Annual Meeting of the American Society of Hematology (#ASH16) is typically a day of multiple oral sessions in parallel.
This year it was a major challenge doing a mad dash between sessions as the meeting is now so big that in San Diego it’s being held, not only at the vast convention center, but is also using the meeting rooms of three nearby three hotels – it’s literally a mile walk to go from one end of the convention to the other, so you have to factor that time into your crazed schedule with multiple clashes.
On the positive side, there’s even courtesy pedicabs – cycle rickshaws (great idea & fun) – I caught one at 7am the other day to save my toes from at least one #blisterwalk…
Following on from our ASH Highlights 2016 Part 1, this post answers critical BSB Reader questions that have come in thick and fast and require more than 140 characters on Twitter to answer.
Predictably, the majority of the first tranche of questions have been CAR T cell therapy related, so if you have a keen interest in this area, this is the post for you. We tackle 5 critical questions and offer some insights.
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