As we move from monotherapies to combinations in the immuno-oncology space, we start to see some intriguing ideas being explored from additional checkpoints to vaccines to neoantigens to immune agonists to oncolytic viruses. There are numerous ways to evaluate how to boost or jumpstart more immune cells upfront in the hope of seeing better efficacy.
One way to do this is to better understand the tumour microenvironment.
Wall of people at ASH16 in San Diego
If we know what’s wrong under the hood, we might be better able to make the immune system get going… more gas, faulty starter motor, dead battery, loose wire, broken fan belt? All these things and more might be a problem so you can see that diagnosing the issue up from from basic and translational work might be instructive for clinical trials.
If you don’t know what problem you’re trying to fix or repair then you might as well be throwing mud at the wall. Just as we don’t expect a car mechanic to suggest changing the battery or starter-motor without first diagnosing the issue, so understanding the tumour microenvironment in each different cancer or disease might also be a helpful strategy.
At the recent American Society of Hematology annual meeting (#ASH16), there was a fascinating sceintifc workshop that focused on this very concept – what’s going on under the hood and how do we go about fixing it?
Here we explore these ideas via an interview with a thought leader and specialist in the field. What he had to say was very interesting and candid indeed.
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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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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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Aloha! It will soon be time to pack your Hawaiian shirts for the forthcoming BMT Tandem Meeting in Hawaii (Twitter #BMTTandem16 – what a long hashtag!!)
Commonly known as “Tandem,” it’s the combined annual meetings of the Center for International Blood & Marrow Transplant Research (CIBMTR) and the American Society for Blood and Marrow Transplantation (ASBMT).
Hawaii is great location for a meeting in February, and one that I’m sure will generate a lot of envy for those who can’t attend and are stuck in the winter cold and chill. Who said we don’t go the “extra mile” for BSB subs?
One of the presentations I’m looking forward to hearing at Tandem is by Ann Leen, PhD, who is an Associate Professor at Baylor College of Medicine.
Dr Leen will be talking about “Immunotherapy for Lymphoma using T cells Targeting Multiple Tumor-Associated Antigens.”
At last December’s ASH annual meeting, Dr Leen presented preliminary data with this novel approach in patients with Hodgkin’s Lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). After her ASH presentation, she kindly spoke to BSB.
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Seattle Genetics ASH 2015 Exhibit – photo with permission
San Francisco – Seattle Genetics are presenting later today at the JP Morgan Healthcare conference (2.30pm PST) and we’ll be covering this as part of our daily rolling blog.
As blog subscribers already know, one of the presentations that caught our attention at ASH 2015 was the updated phase 1 data for Seattle Genetics latest ADC, denintuzumab mafodotin (SGN-CD19A) in B-cell malignancies, including diffuse large B-Cell lymphoma (DLBCL).
Unlike with brentuximab vedotin, where one of the main side effects seen is peripheral neuropathy, with 19A, as it’s commonly known, there is ocular toxicity. Will this toxicity bring the house of cards down for Seattle Genetics?
I spoke to President and CEO Clay Siegall, PhD about this, the company’s corporate strategy moving forwards in 2016 and how checkpoint inhibitors may impact classical Hodgkin’s Lymphoma (cHL).
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Aggressive lymphoma… the very phrase is enough to send chills down your spine!
In the past, much of the focus at previous American Society of Hematology (ASH) meetings in this area has focused on the myriad of chemotherapy regimens and dose/schedule optimisations that followed in trying to boost patient outcomes.
This year, I’m pleased to say that things have quite a different flavour with numerous new therapeutics and promising combinations in development.
Some of these are inevitably hypothesis testing, while others will be up-levelling to large randomised controlled multi-centre trials.
As part of our ongoing preview series, we take a look at the different categories to watch out for beyond chemotherapy. These include monoclonal antibodies, antibody drug conjugates, targeted therapies and yes, even immunotherapies.
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One of the hotly debated topics at the 2014 American Society of Hematology (ASH) annual meeting was the arrival of checkpoint data in classical Hodgkin’s lymphoma (cHL), with initial data presented on 20-30 patients with relapsed or refractory cHL who received either nivolumab (BMS) or pembrolizumab (Merck) in open label, single agent trials.
Updated phase I data is expected to be presented at the 2015 ASH annual meeting in Orlando (Dec 5-8) (Twitter #ASH15)
At the recent ESMO symposium on Immuno-Oncology in Lausanne (Twitter #Immuno15) – great hashtag, there was an excellent overview of checkpoint blockade in lymphomas. What did this tell us about progress in this disease and where are things going?
The ESMO IO meeting set the scene for what we can expect at ASH this year?
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It’s time to answer some more subscriber questions. Several readers wrote in and asked about the anti-PD1 checkpoint data that was presented at the recent American Society of Hematology (ASH) meeting in classic Hodgkin’s lymphoma (cHL):
What did we think of it?
Well, for starters it was one of our highlights of the ASH 2014 conference (see quick write-up, open access), with an impressive 87% response rate for nivolumab in refractory cHL. Many of these patients had failed both autologous stem cell transplant and brentuximab (Adcetris), for which FDA granted breakthrough therapy designation.
Overall, I agreed with Ron Levy (Stanford) when he noted in the packed Special Session on Checkpoint inhibitors in Hematology that there were only 4 or 5 abstracts to actually discuss (he didn’t spend much time on the preliminary data) and that the results are still very early without seeing how good the durability will be.
As he observed in the session, which was standing room only, figuring out how best to integrate these new agents into clinical practice with other successful approaches will be most interesting.
That said, there are some new data that have emerged since ASH that are worthy of discussion in terms of potential future directions and how they could impact the checkpoint landscape in both hematologic malignancies and even solid tumours.
This is part of our ongoing immuno-oncology series on how we can manipulate T cells in creative ways to kill the cancer cells. The findings discussed in this article are completely new and have not been discussed here before.
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San Francisco – do you want to know the difference between Non-Hodgkin’s Lymphoma and Hodgkin’s Lymphoma? Do you want to know what my top 10 abstracts are in Hodgkin’s Lymphoma and aggressive lymphomas that discuss promising new agents in development? Which of these abstracts should have been a plenary at the meeting?
If the answer is “Yes” to the above, then this blog post is for you!
When I consider what is worthy of a plenary presentation at a meeting like ASH, I think back to the Gleevec phase 1 data presented at ASH in 1999 when I was in Novartis Oncology New Products. It’s data that makes you go WOW!, is transformative or has the potential to change the field. That’s what Gleevec did in CML.
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One of the overlooked highlights from ASCO this year was new data in diffuse large B cell lymphoma (DLBCL), which is an aggressive form of Non-Hodgkins Lymphoma (NHL). DLBCL is the most common form of NHL accounting for nearly one third of newly diagnosed NHL cases each year in the USA. Most of these people are adults rather than children.
The first sign of DLBCL is often a painless rapid swelling in the neck, armpit, or groin, which is caused by enlarged lymph nodes. Other symptoms can include night sweats, unexplained fevers, and weight loss.
Aggressive lymphomas such as DLBCL behave very differently from indolent NHL (iNHL) since they are faster growing and generally have a much poorer prognosis. As a result, they are treated much more aggressively with rituximab plus chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Sometimes etoposide (E) is added in younger patients with a high disease burden, in which case the regimen is known as R-EPOCH.
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