What to expect from this year’s ASH: a preview
This year’s Annual Meeting of the American Society of Hematology (ASH) will be held at the Orange County Convention Center in Orlando, FL, December 5-8.
For 2015, there were 798 abstracts dealing with myeloma. The selected abstracts were, as usual, divided into several oral sessions with usually six abstracts per session and several huge poster sessions in the early evening of Saturday, Sunday, and Monday. The presentations start at 7:00 in the morning and run until 8:00 in the evening – a truly grueling schedule!
The selection of the “top” abstracts at ASH is always somewhat personal, but IMF Medical Editor Debbie Birns and I have picked a combination of research and clinically important topics as the “best” this year. The categories of our top picks are:
The idea that minimal residual disease (MRD) should be assessed to achieve better outcomes with novel combination therapy is definitely a key concept of at this year’s ASH. For the IMF, it is wonderful to have Black Swan Research Initiative® investigators such as Drs. Bruno Paiva, Alberto Orfao and Andrew Spencer give oral presentations on their MRD research findings. Alberto Orfao is also the keynote speaker in a special session this year, “The Path Toward Curing Multiple Myeloma.”
As more information is gathered about how to achieve MRD negative status at a 1 per million sensitivity level (10⁶), as well as what it means to achieve sustained MRD negativity, one can consider how to further evaluate MRD positive patients with residual disease and the need for novel alternate approaches to treatment. Studies at the molecular level have revealed different patterns of drug resistance over time, with clones “branching” from the original clone or emerging separate subclones. This knowledge is extremely important to developing strategies to treat resistant residual disease.
3 drugs versus 2 drugs
The use of 3 drugs (triple therapy) versus 2 drugs (doublets) is an important theme this year. I will report the results of the SWOG S0777 trial, which shows that frontline therapy with VRd (triple therapy) versus Rd (doublet) produces longer remissions and survival by about one year for both. This is not to say that a subset of patients may not do extremely well with just the Rd doublet, but VRd produces deeper and longer remissions overall. Several other abstracts assess the benefit with other triplets: VTd; VCd; VMP, VRd-lite (in the elderly) considering comparative short and longer term benefits. For example, Dr. Philippe Moreau from the IFM (Intergroupe Francophone du Myélome) team presents that outcomes are better with VTd versus VCd as frontline induction therapy (ASH abstract #393). It is thus interesting that a theme of excellent outcomes with proteasome inhibitor/iMiD combinations is perhaps reflecting a preferred approach for frontline triplet therapy.
Role of auto transplant
There is a re-emergence of the role of auto transplant at this year’s ASH. Dr. Michele Attal from the IFM team will present the initial findings from the IFM/DFCI trial of VRd plus consolidation and maintenance with or without frontline ASCT (ASH abstract #391). The most recent data will be revealed at the meeting, BUT it appears that there is indeed benefit with frontline ASCT in the setting of maximum novel agent combination therapy. So stay tuned for full details on this important trial. Other presentations will demonstrate the continued need for, and value of auto transplant in the salvage setting and with otherwise resistant disease.
Carfilzomib (Kyprolis®) is another important topic of several presentations. Carfilzomib combinations produce impressively deep responses. One day per week and higher dose schedules produce excellent results. The use of different combinations is helpful for clinician awareness.
The truly newer novel agents are covered in a series of oral and poster sessions. For daratumumab, the ASH presentations are a bit anticlimactic in light of the FDA approval announced this past Monday, November 16, 2015. Daratumumab, the anti-CD38 monoclonal antibody, is now approved for use in the relapse/refractory setting. As we await the possible further approval of elotuzumab (anti-SLAMF7 MoAB) and ixazomib (oral proteasome inhibitor), the newest data presented at ASH are of keen interest. Dr. Meletios Dimopoulous presents the Eloquent-2 trial data in which the Elo-Rd combination produces longer remissions (in patients with 1-3 prior lines of therapy) versus Rd alone (ASH abstract# 28). Dr. Philippe Moreau presents the Tourmaline study results (ASH abstract #727) in which the Ixaz-Rd combination produces longer remissions versus Rd alone. Both are very promising findings which have been submitted for FDA consideration. Early results with the anti-PD-1 (checkpoint inhibitor) are presented with encouraging results with Pembrolizumab plus Rd and pomalidomide/dexamethasone combinations (ASH abstract #506).
Finally, there are quite a number of helpful clinical tips at this year’s ASH meeting: What I call Clinical “Pearls.” The benefit of using the antibiotic doxycycline to treat amyloidosis is unexpected and helpful. There are several helpful tips about the use of newer imaging techniques. Although PET/CT was clearly helpful in the IFM/DFCI trial for response monitoring, MRI was helpful for baseline and relapse assessment in two other studies (ASH abstract #1758 and abstract #4178). It was very reassuring to note that reduction of dosing of dexamethasone reduced toxicity, but also retained efficacy when undertaken in a proactive fashion to sustain ongoing therapy. A summary of Clinical “Pearls” is provided in Table 2—so, many interesting points to consider!
This year’s ASH will definitely be an exciting one and, I suspect, an exhausting meeting, with sequential and parallel sessions from morning to night each day! The new information absolutely improves our understanding of myeloma and will lead to better patient outcomes.
There will be a full report post-ASH! Stay tuned.
Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.