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Posts tagged ‘Diffuse Large B Cell Lymphoma’

SGEN Booth ASH15

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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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 sign up or sign in below…

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