I just got back from this year's meeting of the American Society of Hematology. As always, there was lots of research progress reported and researchers funded by The Leukemia & Lymphoma Society (LLS) were well-represented. It was an opportunity to learn more about the biology of various forms of lymphoma and about evolving treatments for patients with Hodgkin and non-Hodgkin lymphomas (NHL).

The NHL Education Program was opened by Elaine Jaffe, M.D., from the National Cancer Institute. She described the 2008 World Health Organization (WHO) classification of NHLs - this new schema uses the myriad of recently discovered molecular abnormalities to better distinguish NHL subtypes, with clear implications for more individualized and optimized treatments, including targeted therapies. Lymphoma cells can be found in the blood, bone marrow, lymph nodes and many other sites such that subtypes are not best distinguished by presentation site, but rather by specific molecular abnormalities and the normal cell type from which they apparently evolved. Of note, chronic lymphocytic leukemia (CLL) has been recognized for some time as a mature B-cell lymphoid cancer and the WHO classification has clarified molecular and biological distinctions between CLL  and lymphoma subtypes, such as small cell lymphoma (SLL).

LLS-funded Steven Bernstein, M.D., of the University of Rochester, was the second featured speaker in this session - he discussed the transformation of some cases of relatively indolent follicular lymphoma into aggressive cancers, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma and histiocytic or dendritic cell sarcomas. It seems that particular molecular abnormalities make transformation more likely and that risk may be increased by treatments with high doses of alkylator or purine analog drugs. Rituxan® apparently does not affect the risk of transformation and importantly the Rituxan-containing combination therapy known as R-CHOP seems to be effective for many patients even after transformation.

Dr. Bernstein reviewed the use of autologous, allogeneic and reduced intensity ("mini") stem cell transplantation for these patients, including transplants in which radioactive antibody therapy is used as the conditioning regimen. He said that well-designed clinical trials are desperately needed to determine which approach is best for patients with particular molecular and clinical characteristics. I have talked here before about clinical trials and their importance to improving outcomes for cancer patients.

In a subsequent session. LLS-funded Jonathan Friedberg, M.D., of University of Rochester was the senior author of a report regarding a Phase 3 clinical trial that compared three possible treatments for patients with Mantle Cell Lymphoma (MCL). MCL is an uncommon subtype of NHL with a generally unfavorable prognosis, and the role of aggressive induction therapy versus sequential standard chemotherapy remains uncertain, particularly in younger patients. This was a multi-center clinical study that also involved LLS-funded Andrew Zelenetz, M.D., at the Memorial Sloan Kettering Cancer Center.

Patients less than 65 years old were newly diagnosed with MCL at the seven participating cancer centers between August 2000 and February 2009, randomized to treatments with standard R-CHOP chemotherapy, R-CHOP followed by high dose therapy and autologous stem cell transplantation, or the so-called R-Hypercvad therapy. 156 patients were included in the final analysis with a median follow-up of 30 months at this report that showed that the newer regimens were equally effective and significantly more effective than R-CHOP, with approximately twice as many patients surviving progression-free at two years. These results are also likely to apply to patients with other aggressive forms of NHL But the median progression-free survival was still just three years and these researchers urged that future trials for lymphoma patients focus on novel agents.

LLS-funded Irene Ghobrial, M.D. of the Dana-Farber Cancer Institute presented results of a Phase 2 trial testing one such novel drug for patients with Waldenström macroglobulinemia (WM), a rare blood cancer that has features in common with lymphoma and myeloma. She and her Dana Farber and Mayo Clinic colleagues tested an oral drug that inhibits the mTOR molecule which controls cell proliferation and survival and is involved in many cancers including lymphomas. I have talked here before about mTOR targeting therapies. Afinitor® (everolimus, RAD001) was recently FDA approved for patients with advanced kidney cancer. Dr. Ghobrial and her colleagues set out to determine whether single-agent Afinitor could help patients with relapsed/refractory WM. 50 patients were treated, with an overall response rate of 70%, estimated progression free survival of 62% at 12 months, and manageable toxicity. Trials of this and other mTOR inhibitor drugs are underway and a follow-on study is planned for WM patients, based on these promising results.

Treanda® (bendamustine) was recently approved for the treatment of CLL patients and relapsed/refractory NHL patients. Although its exact mechanism of action is unknown, this drug appears to act primarily as an alkylator drug that inhibits DNA, RNA and protein synthesis and thereby kills cells, especially actively proliferating cells like cancer cells. Dr. Zelenetz (mentioned above) was a member of a team that showed that Treanda is also highly active in heavily pre-treated patients with relapsed/refractory Hodgkin lymphoma and can be used to get patients into a remission before reduced intensity stem cell transplantation.

Of course, the emphasis on new molecularly targeted therapies is driven in part by the fact that many of today's standard anti-cancer drugs kill proliferating cells non-discriminately and also can cause mutations in normal cells, potentially causing new cancers. Therapy-induced myeloid cancers are currently the leading cause of non-relapse deaths in patients treated for NHL or Hodgkin lymphoma.  Smita Bhatia, M.D., M.P.H., of the City of Hope Medical Center, was senior author of a large study that identified risk factors for these secondary cancers and found that alternative forms of specific molecules that control DNA repair, programmed cell death and cancer drug metabolism are associated with significantly increased risks. These results not only help us understand how secondary cancers occur but also set the stage for rational surveillance and targeted intervention strategies.

Research progress continues - stay tuned!