By James Foran, MD

2008-12-08

Today will be a busy day for lymphoma doctors. An impressive array of new targets, new agents, and new monoclonal antibodies, as well as studies of PET imaging and novel combination strategies will be presented at the lymphoma oral sessions today. In all, there will be 11 separate oral sessions from 7:00 a.m. to 7:15 p.m. (not including CLL), covering B- and T-cell biology, prognosis, imaging, therapy, new agents, and preclinical studies.

The day starts early with competing sessions at 7:00 a.m. titled New and Emerging Biologic Therapies (Room 3001-3003-3005 – West) and Targeted Therapies and New Agents in Lymphoma (Room 2005-2007-2018-2020 – West). These include presentations of immune-mediated treatments of lymphoma, as well as studies of new agents, new combinations, and novel monoclonal antibodies. The role of consolidation with radiotherapy remains controversial in lymphoma, as does the value of interim PET scanning, and prospective studies from the United Kingdom, United States, and Germany evaluating the utility of both of these strategies will be presented later in the morning in the Hodgkin Lymphoma – Interim PET in Lymphoma session (11:00 a.m. in Room 2005-2007-2018-2020 – West). Interestingly, in a presentation earlier in the morning, PET scanning is used as a correlative study to demonstrate proof of mechanism of a cyclin D-dependent kinase inhibitor in mantle-cell lymphoma in a study by Dr. John P. Leonard (abstract #264).

Later, in the Diffuse Large B-cell Lymphoma: Biology and Prognosis session (1:30 p.m. in Room 3001-3003-3005 – West), new molecular prognostic factors are presented. This includes an interesting study by Dr. Davide Rossi (abstract #480) of the impact of host pharmacogenetic background (using candidate single nucleotide polymorphisms) and its association with clinical outcomes (toxicity and event-free survival) after R-CHOP chemotherapy for diffuse large B-cell lymphoma. In the afternoon, Clinical Studies in Lymphoma (Room 120-125 – North) will include presentations on new treatment strategies and new prognostic markers, while in DLBCL and Other NHL: Novel Therapeutic Targets and Approaches, preclinical studies of new agents will be presented. Both of the latter sessions start at 3:30 p.m. in Room 3006-3008 – West. Finally, studies of B-cell biology are presented later in the day, with Low Grade B-Cell Lymphoma: Biology, at 3:30 p.m. (Room 3001-3003-3005 – West), followed by B-Cell Biology at 6:00 p.m. (Room 2006-2008 – West).

The breadth of the new therapies being presented is both fascinating and astounding. They include immunotherapeutic strategies ranging from the use of autologous cytotoxic T-lymphocytes targeting EBV latent membrane proteins in EBV+ lymphoma (Bollard, et al., abstract #230) to reduction in immunosuppression as treatment for post-transplant lymphoproliferative disorders (Cheema, et al., abstract #229). Results of the strategy of lymphoma-derived idiotype (Id) vaccination is also being presented, including both positive trials (e.g., early-phase study of Id expressed as a recombinant Fab fragment) and negative trials (e.g., phase III placebo-controlled study of adjuvant mitumprotimut-T (Id-KLH and GM-CSF).

There is continued great interest in the development of new or “optimized” monoclonal antibodies in lymphoma, including radio-labeled anti-CD25 (Y90-labeled daclizumab), SGN-30 (anti-CD30), GA101 (humanized and glyco-engineered anti-CD20), and the anti-CD22 immunotoxin inotuzumab ozogamicin in combination with rituximab. Encouraging responses are also noted with blinotumomab, a BiTE antibody targeting CD19.

New targeted kinase inhibitors being presented include BI 2536, targeting the Polo-like kinase 1, and fostamatinib disodium (targeting the spleen tyrosine kinase SYK), which was presented at the Plenary Session yesterday.

Presentations in peripheral T-cell lymphoma include a multicenter trial of pralatrexate (with B12 and folic acid), reporting impressive activity, and a study of romidepsin (a pan-HDAC inhibitor), reported to show clinical benefit in refractory cutaneous T-cell lymphoma. The use of a novel intensive treatment strategy for enteropathy-associated T-cell lymphoma (including autologous stem cell transplantation) suggests improved survival in a sequential study from the Scotland & Newcastle Lymphoma Group.

I know it will be a great day, and it will certainly be a long day. After the oral sessions, you should attend the lymphoma poster sessions from 5:30 to 7:30 p.m. If I see you there and you can still utter the word “lymphoma” coherently, I will congratulate you personally!

Dr. Foran indicated no relevant conflicts of interest.

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