January-February 2017, Volume 14, Issue 1
The ASH Annual Meeting: 58 Years of Advancing Hematology, and Counting
Published on: January 01, 2017
The 58th ASH Annual Meeting: While not a diamond jubilee, with every year that passes, we celebrated discoveries in hematology that translate into better lives for our patients. The Hallmark Company, in its semi-authoritative list, declares that the theme of 58th anniversaries is faith and hope. In the clinic, immediately after the annual meeting, patients invariably begin probing, shortly after the obligatory small chat about the weather: “So, what I really want is the news from that big hematology meeting you were just at.” Although they might not fit in my luggage with the sports coats and bowties, every year I take my patient’s hopes with me to the meeting, looking for that next breakthrough. The other half of this theme is faith – faith that we can move the needle forward in the understanding and care of patients with hematologic disorders. Augustine of Hippo described the reward of faith as, “to see what you believe.” During this annual event, we see the results of our commitment and hard work come into view.
The Scientific Plenary Session is always a source of inspiration and this year was no exception. As covered in the ASH News Daily article “A Vector of Hope for the Future of Hemophilia,” results from a phase I/IIa study of a hemophilia B gene therapy that harnesses the FIX-Padua transgene were reported. By using the FIX-Padua transgene, there is increased FIX activity, so a lower vector dose can be used to minimize the need for immunosuppression while still obtaining therapeutic FIX levels of around 30 percent. With the exception of one subject who had two suspected joint bleeds requiring factor replacement, all other subjects stopped their prophylaxis, did not require any factor replacement, and had no breakthrough bleeding in 238 cumulative weeks of follow-up.
Sickle cell disease (SCD) was an area of great emphasis as advancements and unmet needs in this disease were thoroughly discussed during this year’s meeting. In the middle of ASH Central, right next to the collaboration rooms and selfie station, two sculptors worked a pile of amorphous beach sand into a monument, bringing to life the effort to cure this illness. The sands of time are shifting for this disease as we are now emerging from the drug desert. The SUSTAIN trial, which compared the P-selectin antibody SelG1 against hydroxyurea, captured headlines after its presentation at the Plenary Scientific Session. This is the first randomized controlled trial in more than a decade to demonstrate a significant reduction in SCD pain crises. This year’s Presidential Symposium highlighted state-of-the-art molecular pathways that have hoisted SCD research to new heights, including chromatin remodeling and fetal hemoglobin modifying genes, in addition to gene therapy. The sky is the limit for the future of SCD treatment. To continue this upward momentum, the funds raised by the 2016 ASH Foundation Run/Walk this year have been earmarked to support ASH’s Sickle Cell Disease Initiative, a top priority for the Society.
Many of the questions that I get from patients in clinic revolve around genomics. Everything from, “Did I pass along this disease to my children?” to “Since this disease has a mutation, can you use that gene editing stuff to fix it?” Likewise, the genomic basis of hematologic cancers continues to be a major theme at the annual meeting. A few years back, ASH News Daily, not known for passing up a good pun, quipped, “Do These Genes Make My Cancer Look Bad?” While we are still assembling the complete picture of somatic mutations’ influence on hematologic malignancies, one of the new Friday Scientific Workshops focused on the role that germline mutations play in developing hematologic malignancies. Estimates often quoted in textbooks and talks suggest that roughly 2 to 4 percent of patients with hematologic neoplasms develop these diseases as a result of an underlying inherited predisposition. However, these numbers likely underestimate the true prevalence. This session certainly shined a light on the contribution of inherited predisposition alleles to disease susceptibility. Results of experiments using gene editing techniques were seen across the oral and poster session and were covered in a special-interest session on CRISPR. Furthermore, in the Plenary Scientific Session, we saw a newly identified inherited monogenetic disease involving SMARCD2, which uncovered its role in neutrophil maturation and prevention of leukemogenesis.
In addition to breakthroughs in understanding the biology of disease, we also saw the results of potentially practicechanging randomized controlled trials, making waves across treatment landscapes. The results of the GALLIUM study were no exception. The GALLIUM study pitted the two heavyweights of obinutuzumab-based chemoimmunotherapy versus rituximabbased chemoimmunotherapy, both with continued anti-CD20 maintenance therapy. While the overall survival data have yet to mature, there was a progression-free survival benefit seen in the obinutuzumab arm, with a 34 percent decrease in progression or death compared with the rituximab arm. There was some increased toxicity seen with obinutuzumab, and of course the impact on health-care resources and overall survival will need to be analyzed prior to a shift in practice. We also had the privilege of hearing the results of several large randomized trials in transplantation. During the Late-Breaking Abstract session, the results of the StaMINA trial showed that tandem autologous transplantation for newly diagnosed multiple myeloma was not superior to a single transplant. This was not without controversy, as the EMN02/H095 MM trial presented the next day arrived at the opposite conclusion. The devil is in the details, and the different induction regimens in these two trials may account for the conflicting results.
“Less is more” may be the anthem to the post-World War II minimalist movement in art and architecture, but it may also describe a recent movement in hematology. The goal of phase I trials has been to determine the maximum tolerated dose; therefore, we do not always know what the minimum effective dose will be. Perhaps less is more — by cutting back on the intensity or duration of treatment, efficacy can be maintained while turning down the toxicity associated with that treatment. Several abstracts at the annual meeting took this approach, with differing results. The AIEOP-BFM ALL 2000 trial was a randomized, noninferiority trial that compared an abridged chemotherapy regimen for pediatric acute lymphocytic leukemia to that of a standard extended regimen in standard-risk patients (negative for minimal residual disease at both days 33 and 78 after the start of induction therapy). Ultimately we saw that this attempt was not successful due to evidence of more relapses observed in patients treated less intensively. Numerous abstracts featured the reduction or discontinuation of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). Six months after stopping their TKI, patients with chronic-phase CML in deep molecular remission experienced a molecular relapse-free survival of 62 percent in the EURO-SKI trial. For those patients who did not have molecular relapse-free remission during the study, the majority regained their deep molecular remission when TKI was restarted, and none advanced to blast phase. The results of the British DESTINY Study added that in patients who have a stable molecular remission (MR3 or better), we may be able to safely reduce the dose of their TKI by half, which was associated with an improvement in TKI-related adverse effects.
With the wide assortment of sessions and the 6,646 abstracts presented, this wrap-up is a very narrow slice of the 2016 annual meeting. As the Editor of the ASH News Daily, I was able to experience the meeting from a view beyond my niche, and really appreciate the recurrent themes woven across the five days in San Diego. From there it was easy to see the progress being made and have hope and faith in hematology’s future. If you were unable to attend the meeting, or missed any of the ASH News Daily articles, catch them online at www.hematology.org/ashnewsdaily. I look forward to seeing you in Atlanta in 2017.
Conflict of Interests
Dr. Gerds indicated no relevant conflicts of interest.
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