Pathways to success with small molecule developments
It always amuses me when people describe the small molecule space in lymphomas as ‘neat and ordered’ when in reality, it is anything but…
After all, not all patients respond initially, some cannot tolerate the side effects, and additional mutations can be acquired in response to therapy inducing acquired resistance and sometimes more aggressive disease results.
How do we go about addressing all of these issues in order to improve outcomes further?
We can certainly get a few ideas from the early stage pipelines being evaluated, as well as from the kind of combination regimens currently being developed. What do the results show?
Then there’s a raft of quite unrelated agents which might be competitive and could usurp existing approaches should they move earlier up in the treatment paradigm. Plenty of Pharma execs have certainly been caught out in the past not keeping their eyes on the right eight ball.
In our latest ASH20 Preview we highlight a few intriguing abstracts to watch out for at the forthcoming meeting this weekend…
To learn more from our oncology analysis and get a heads up on the latest insights and commentary pertaining to the ASH meeting — including our latest preview of the 2020 abstracts, subscribers can log-in or you can click to gain access to BSB Premium Content.
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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Over the last two years there has been a lot of focus on indolent lymphomas (iNHL) and chronic lymphocytic leukemia (CLL) with numerous new targeted therapies being tested in clinical trials including ibrutinib (Imbruvica), idelalisib, ABT–199 and IPI–145 to name a few.
What about diffuse large B cell lymphomas (DLBCL) though? These are much more aggressive and generally have a poorer prognosis than indolent lymphomas.
Standard treatment upfront for DLBCL is R-CHOP i.e. rituximab plus chemotherapy i.e. cyclophosphamide (C), doxorubicin hydrochloride (H), vincristine/Oncovin (O) and prednisone (P). R-CHOP is usually given in cycles every 3 weeks (R-CHOP21) and most patients receive between 3 and 8 cycles. Sometimes R-CHOP is given every two weeks (R-CHOP14) in a more intensive fashion, although the dose dense regimen has not been shown to improve progression-free survival (PFS). In younger patients with a high disease burden, etoposide is sometimes added to the chemotherapies, making the regimen R-EPOCH.
One of the biggest challenges with treating this disease is that some 40% of patients do not respond to salvage therapy after initial treatment with R-CHOP, making it an area of hugh unmet medical need.
The good news is that there were a number novel and interesting therapies in development with promising data in Chicago. Previously, we discussed the promising data from the antibody drug conjugates (ADCs) from Genentech and Seattle Genetics, including SGN-CD19A, polatuzumab vedotin and pinatuzumab vedotin. This article takes a look at other therapies in development for DLBCL, including TKIs and the promise of some of the earlier therapies in the clinic:
Agents mentioned: lenalidomide (Revlimid), GS–9973, cerdulatinib (PRT062070), IMGN529, TAK659, selinexor, ND–2158
Companies mentioned: Celgene, Gilead, Roche/Genentech, Portola, Immunogen, Millennium/Takeda, Karyopharm, Nimbus Discovery
To learn more about part 2 of our series on DLBCL and aggressive lymphomas, you can log-in to read the article.