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…
Chronic lymphocytic leukemia (CLL) and indolent non-Hodgkins Lymphoma (iNHL) have received significant attention over the last two years. More exciting new therapies than ever before – with multiple different mechanisms of action – have either recently come to market or are in development. There is an ongoing revolution in the CLL landscape and treatment of the disease, which above all else is good news for patients! As part of our ongoing longitudinal coverage, there’s a lot to discuss and catch up on in Chicago at the annual meeting of the American Society of Clinical Oncology (ASCO).
What’s different at ASCO this year?
Basically, a LOT more data – it’s almost a tsunami considering this is ASCO and not the American Society of Hematology (ASH) annual meeting! I am excited to see that there is so much new data at ASCO. Yesterday, we highlighted 3 key sessions for multiple myeloma. For CLL/SLL and iNHL there are 9 – to put the sheer breadth of data and studies in context. This includes ongoing phase 1-3 trials, as well as new randomised controlled phase 3 studies that are now open and enrolling patients. If successful, some of these latter studies will play a crucial part in future registration packages to the Health Authorities. In the past, we have talked extensively about CD19 antibodies such as obinutuzumab (Gazyva) and BTK inhibitors such as ibrutinib (Imbruvica). Both of these drugs are now approved and available in the US.
Other therapies in development we have covered in the past have included PI3K inhibitors delta (idelalisib) and delta, gamma (IPI-145), as well as Bcl2 inhibitors (ABT-199 / GDC-0199), SYK inhibitors (fostamatinib and GS-9973), and CAR T cell therapies such as CTL019. To find out more about our insights on the ever-changing CLL landscape, you can sign in or sign up below.
Now that the last of the 2013 cancer conference season is finally over, we’re going to run a couple of post meeting summaries this week from ASH as a few subscribers have asked for the Cliff Notes version of what was hot – or not in the context of the market.
New treatments for Chronic Lymphocytic Leukemia (CLL) was one of the hot topics at the recent annual meeting of the American Society of Hematology in New Orleans.
Hot on the heels of Roche’s recent FDA approval for Gazyva (obinutuzumab/GA101) in CLL, other companies in the race to market including:
- Pharmacyclics and Johnson & Johnson (ibrutinib)
- Gilead (idelalisib, GS-9973)
- Infinity (IPI-145)
- AbbVie and Roche (ABT-199/GDC-0199)
- Novartis (CTL019).
Here’s my subjective and personal assessment of the winners and losers based on the data presented:
The chronic lymphocytic leukemia (CLL) landscape has been one of the most dynamic and exciting over the last 12 months, with many new therapies emerging against different targets from CD20 to BCR signaling, Bcl2 to the PI3K pathway. Other new targets may also soon emerge.
The annual meeting of the American Society of Hematology (ASH) in New Orleans sets the scene for the rollout of more mature data and affords an early evaluation of where the various companies competing in this space may shake out. Given that we are moving beyond traditional chemoimmunotherapy to evaluate several newer classes of therapy including B cell receptor (BCR) and PI3K signaling, anti-CD20 antibodies, anti-CD19 chimeric antigen receptor T cell technology (CART) it looks to be shaking out to an exciting conference.
Companies mentioned: Roche/Genentech, Gilead, Pharmacyclics, Abbott, Celgene, Infinity, Incyte, ONO, Amgen, TG Therapeutics, Novartis
Products discussed: rituximab, bendamustine, obinutuzumab, idelalisib, ibrutinib, ABT-199, CC-292, GS-9973, IPI-145, ONO-4059, INCB40093, AMG 319, TGR-1202, CTL-019
THE data of the 2013 annual meeting of the American Society of Clinical Oncology (ASCO) that starts later this week
In my final post from the 2013 annual meeting of the American Association for Cancer Research (AACR), I wanted to