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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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.