Clinical Advances in Hematology & Oncology

January 2017 - Volume 15, Issue 1

Letter From the Editor: The ASH Rehash

Brad S. Kahl, MD

As I sit down to compose my first Letter From the Editor, I must admit to a certain amount of insecurity. For the past 14 years, Bruce Cheson has been filling this space with somewhat personal and quite entertaining columns. We have read about his family, dog(s), wine choices, travel, bike rides/fund-raisers, book clubs, fellowship interviews, and even political views. I enjoyed these columns—Bruce writes beautifully, better than I. (Or is it “better than me”? Bruce would know.)

During my tenure as editor-in-chief, we will continue to focus on bringing the reader timely, practical, and concise reviews and overviews. The explosion of knowledge and new therapeutics in hematology and oncology has made it nearly impossible to stay current. We will do our best to close knowledge gaps, and your suggestions for future topics will be greatly appreciated.

What to focus on in month 1? Easy—the 2016 ASH meeting. This is the premier hematology meeting of the year, and I always return home buoyed by the advances. Plus, in my humble opinion, San Diego is the best ASH venue. Nice convention center, plenty of nearby hotels, quality restaurants in the adjacent Gaslamp Quarter, fabulous weather, close airport. What’s not to like? I have suggested that ASH commit to a 5- to 10-year run there, as ASCO has done with Chicago. That’s unlikely to happen, but at least I’ve put it out there.

The meeting had its usual logistical challenges, with several rooms not large enough for well-attended oral sessions. I arrived at one session 15 minutes early and was one of the last people let into the room. The poster hall was too small, and attendees could not navigate through the mass of people. (I worry that the corporate area is getting larger at the expense of the posters.)

Like Bruce, I am a lymphoma and CLL doc, so my writing will often be on those disease areas. It was the preliminary results from GALLIUM, a phase 3 trial of obinutuzumab-based induction and maintenance therapy in patients with previously untreated follicular lymphoma, that put my brain in overdrive. Dr Robert Marcus presented the results at the plenary scientific session. (Disclosure: I periodically consult for Genentech/Roche, which sponsored the trial.) Obinutuzumab (O), a novel anti-CD20 monoclonal antibody, has a few properties that might make it better than rituximab (R). It certainly seems a bit better in CLL. The researchers randomly assigned more than 1200 patients worldwide to 6 cycles of either O + chemotherapy or R + chemotherapy, followed by maintenance O or R for 2 years. Each participating center selected a chemotherapy backbone, with the option of bendamustine, CHOP, or CVP. The rates of chemotherapy use were approximately 60% for bendamustine, 30% for CHOP, and 10% for CVP.

The trial demonstrated a statistically significant reduction in the risk for progression or death in the patients assigned to O + chemotherapy. The hazard ratio was 0.66, which equates to a 34% risk reduction. At the landmark of 3 years, 80% of the O + chemotherapy patients were in remission vs 73% of the R + chemotherapy patients. No overall survival differences were observed. The O-treated patients had slightly more infusion reactions, episodes of cytopenia, and infections than the R-treated patients had, and I heard some investigators declare that O is more toxic than R. Although technically true, I did not find the toxicity differences to be clinically meaningful. I had other issues. Most notably, more anti-CD20 monoclonal antibody was given to the patients randomly assigned to O than to the patients assigned to R. To put this in concrete terms, I used 2 hypothetical patients, both assigned to bendamustine and both exactly 2 square meters in size, to perform a calculation. The patient assigned to R would receive 13,500 mg of antibody for the duration of therapy, whereas the patient assigned to O would receive 21,000 mg of antibody. So the O patient would receive 36% more drug, which is eerily close to the 34% risk reduction. A couple of the questions following the presentation centered on this issue, and Dr Marcus argued against the dosing as the difference maker. I remain uncertain, however, and have been trying to think of ways this question could be addressed in future trials. The data set also raises some other interesting issues, such as the higher risk for death in the patients assigned to bendamustine. But I am running out of space, so perhaps we will save that until next month. . . .


Brad S. Kahl, MD