Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘DLBCL’

Are new pillars emerging in DLBCL?

It’s time to take a short break from the immunometabolism mini-series and turn our attention to aggressive lymphomas such as diffuse large B cell lymphomas (DLBCL).

This week heralded the latest AACR virtual meeting on Advances in Lymphoma in conjunction with iCML.  There were plenty of science focused talks to listen to and learn from, including new developments in oncogenic targeting.

What if we can learn from what the patients underlying biology can teach us in terms of more rationally designed clinical trials?

We know these are diverse and heterogeneous tumours, but this doesn’t mean we can’t take a more precision medicine approach to treating patients.  What can we learn from early trial readouts and genetic analyses?

It turns out, the answer is quite a bit and more information might be available at the forthcoming ASH meeting, so let’s look at what we can piece together from the available data now…

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In our latest company interview we continue our ongoing AACR series on various protein degraders and how they may be useful in hitting difficult targets where small molecule TKIs have struggled mightily for various reasons, which we discuss in detail.

The protein degraders are what we might call large small molecules – they have a large molecular weight in Dalton terms – yet despite their unwieldy size they do offer a number of distinct benefits, which could potentially lead to improved efficacy, reduced toxicity, and enhanced outcomes in the setting of both cancer and autoimmune disease.  At least this is nice in theory, but what actually happens in practice?

Can we learn from the preclinical rationale and experiments to get a sense of what might happen in the clinic?

Find out more about what one emerging young biotech are accomplishing on the protein degradation front in both hematologic malignancies and solid tumours…

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Virtual meetings mean we miss the fun of German pop-up sausage stands and focus solely on the new emerging clinical data!

EHA25 Virtual, Not-In-Frankfurt – There’s a lot of commercial interest in CD20 x CD3 bispecifics, and in this post we’re taking a look at some of the latest clinical data presented at recent ASCO and EHA virtual meetings. Companies mentioned include Regeneron, Roche/Genentech, Genmab/Abbvie, Xencor, and IGM Biosciences.

Any analysis of a rapidly evolving and fast-moving landscape only represents a snapshot in time at the point it was taken, and this post is not intended to be a comprehensive landscape report, you’d pay a lot more than a yearly sub to BSB for that, but we’ve been following the field, and there are some trends emerging.

What makes it interesting is there is some nuance required in the interpretation of data, and with that in mind we spoke to an investigator at the forefront of clinical research who has done trials with several of the CD20 x CD3 bispecifics in development; the insights were quite illuminating.

This post offers an update on the CD20 bispecific landscape, analysis of some of the recent data at EHA and ASCO, as well as expert opinion, what more could you ask for?

To read our latest expert interview, and gain insights from our oncology analysis and commentary around data emerging from the ASCO and EHA virtual meetings, subscribers can log-in or you can click to gain access to BSB Premium Content.

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What stood out at TCT in Orlando?

Orlando – There have been numerous useful insights into the future of next generation of CAR T cell therapies at the Transplantation and Cellular Therapy Meeting (TCT) that’s currently underway here in Florida.

TCT (formerly BMT Tandem) is the combined meeting of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR).

It should come as no surprise that the transplant community have embraced cellular therapies.

As we start what experts such as Carl June refer to as “the decade of cell therapy,” what does the next generation of CAR T cell therapy likely look like and how will we overcome some of the challenges associated with this approach?

In this post we’re following developments in the field, and sharing what we’ve learnt so far from thought leaders at the TCT meeting. This is the latest in our recent mini-series of posts on future developments in cellular therapy.

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When should someone receive CAR T cell therapy? How do we identify who will benefit most or who will be most likely to fail? Those are some of the questions we’re considering in our latest expert interview.

As we see the landscapes around aggressive lymphomas and multiple multiple evolve and change with more near-term CAR T cell therapy approvals coming, so too do the clinical questions surrounding the optimising of these novel approaches.

Prof John Gribben, President of EHA (right) at CART2020 in Sitges

At the EHA/EBMT 2nd European meeting on CAR T cell therapy, BSB spoke with Professor John Gribben. He’s the current President of the European Hematology Association (EHA) and holds the Gordon Hamilton Fairley Chair of Medical Oncology at St. Bartholomew’s Hospital, Barts Cancer Institute, Queen Mary, University of London.

One of his messages was when considering CAR T cell therapy, it’s a delicate question of balance.

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ASH19 in Orlando, FL

Orlando: In the second of our ASH19 reports, we offer a comprehensive and in-depth look at important data presented over the weekend where we breakdown some of the key findings or trial readouts, which are likely of interest to many readers given the heightened attention on novel therapeutic approaches.

Whether the hematologic malignancy is myeloma, leukemia, or lymphoma, we have been rather spoiled for choice in selections for hot topics to discuss this year, so the series will likely run all week!

Here’s the second of our detailed ASH notes…

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Friday at #ASH19 – remains of the day or hope springs eternal with sunrise on Saturday morning?

Orlando: The annual meeting of the American Society of Hematology or ASH (Twitter #ASH19) is one of the four key Majors on cancer-related related research meeting circuit that BSB attends each year.

Just as golf has the Masters, the US Open, the Open, and PGA championships, so those on the cancer new product development circuit attend AACR, ASCO, ESMO, and ASH.

This year ASH is in sunny Orlando where you have to compete with the tourists for Uber rides if you want to venture to restaurants or events in the area.

Friday at ASH has traditionally been associated with the satellite symposia, colloquially known as “Super Fridays” that CME companies or organizations such as the Leukemia Lymphoma Society have traditionally run, but in recent years ASH has put on its own Friday events to compete with both the industry satellites and also academic events such as the BMT Winter Workshop we have attended in the past.  More choice is good on one hand, but bad on the other in that something has to give way.

Ron Levy (Stanford) and Stephen Ansell (Mayo) blazed the trail a few years ago with their Friday Scientific Workshop on Tumor Immune Interactions in Lymphoid malignancies. Regular BSB readers may recall the interview at ASH16 with Dr Levy where he reviewed some of the data in that year’s workshop (See post: Targeting the tumour environment in lymphomas.)

This year on Friday at ASH19 there were multiple scientific workshops you could attend. What were some of the presentations that caught our personal attention, what can we learn from them and why did they matter?

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Lugano: This post offers a rundown and synopsis of a wide variety of lymphoma trials across different subsets coming out of the 15th International Conference on Malignant Lymphoma (iCML) being in Lugano, Switzerland this week.

Lugano is a glorious place to hold a meeting!

The meeting is held every two years on odd years, usually after the EHA conference.

As such, this review may well turn out to be a useful reference point for later offering background and context for the upcoming ASH meeting in December, since there will likely be additional trial updates and readouts in Orlando.

Some of the updates on the early phase 1/2 trials reference preclinical posters from old AACR meetings circa 2012–2014, which is why the Gems from the Poster Hall series can often turn out to be useful predictors of later clinical trials performance!

There’s a lot to cover and discuss this year and some intriguing developments under the radar…

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Over the last five years we have followed the trials and tribulations of CAR T cell therapies in ALL and aggressive lymphomas as Novartis, Kite, Juno, Cellectis, Unum and others have undertaken the road less travelled towards filing and approval.

The ASH DASH in action!

Now that we have seen the first two CAR T cell approvals in pediatric ALL (Novartis) and aggressive lymphomas (Kite), with tisagenlecleucel widely expected to be the next one in aggressive lymphomas following presentation of the 6-month JULIET data at the recent American Society of Hematology (ASH) meeting in Atlanta, a key question remains to be addressed:

Is there a threat on the horizon that might be potentially used prior to CAR T cell therapy in refractory lymphomas?

We say ‘yes, there is’ and thus it was interesting to see where this approach might go… including discussion with an expert.

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In our latest thought leader interview from the annual meeting of the American Society of Hematology (ASH) Dr John Leonard (Weill Cornell) provides a lesson on how to interpret key lymphoma data such as ECHELON–1, CAR T cells, and other topics at ASH, as well as what he’d like to see more of in lymphoma clinical trials.

In this hard-hitting interview, Dr Leonard reminds us that the media should not be a mere extension of the PR of companies. Instead he offers his real world insights into what may or may not be practice changing, and how we should interpret CAR T cell therapy data.

Dr John Leonard (Weill Cornell)

It’s a must read for anyone with an interest in lymphoma… here’s an excerpt to give you a flavour of the wide ranging discussion:

 

 

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