The 50th annual meeting of the American Society of Clinical Oncology (ASCO) is in Chicago from May 30th until June 3rd. Compared to the hundreds of myeloma abstracts presented at the annual meeting of the American Society of Hematology (ASH), far fewer ASCO abstracts focus on myeloma. Nonetheless, there are more than 50 myeloma-related abstracts in various oral and poster sessions during the meeting.
Most abstracts reflect recurrent themes from ASH 2013, including: updates on the anti-CD38 agents daratumumab (Abstract #8513) and SAR 650984 (Abstracts #8532 and #8512); the value of continuous (versus fixed duration) therapy, especially with lenalidomide (RevlimidÂ®) (Abstracts #8515 and #8516); predictive and prognostic testing for patients with smoldering myeloma (Abstracts #8587, #8595 and #8604); comparison of novel agents (Abstract #8511 - MPT vs. MPR); and updates on pomalidomide efficacy (Abstracts #8593 and #8589). Data being presented for the first time are the data on the HDAC inhibitor panobinostat from the Panorama I trial in relapsed and refractory myeloma (Abstract #8510).
Let's start with the panobinostat abstract - for which detailed outcome results are presented for the first time, with Dr. Paul Richardson as the first author. This trial is a randomized phase 3 study of panobinostat vs. placebo combined with bortezomib (VelcadeÂ®) plus dexamethasone in relapse/refractory myeloma. The panobinostat significantly improves the progression-free survival (PFS) and duration of response, plus produces higher overall response and especially deeper responses with higher VGPR and/or complete remission (CRs). Important toxicities were increased fatigue, plus platelet-count reductions and diarrhea, which led to discontinuations of therapy in that arm of the trial. There is great anticipation about these results and the implications for potential regulatory review and approval for panobinostat.
Key aspects of the other abstracts presented at ASCO 2014 include the following:
- Anti-CD38 results: The daratumumab and SAR 650984 results continue to be very promising. For daratumumab, the single agent ("monotherapy") results are excellent with administration at higher dose levels (13 patients were given 16mg/kg vs. 30 patients given 8mg/kg), which gave an impressive overall response rate of 46% in relapse/refractory myeloma. For the SAR 650984 antibody, both single agent and combination (with Revlimid/dexamethasone) results will be presented by Dr. Tom Martin from UCSF, again with very good results. The single agent study showed an overall response rate of 33% at the higher dose of 10mg/kg dose (18 patients). In a late-breaking abstract excellent responses will also be reported, including deep responses, with the combination of Revlimid plus dexamethasone.
- There is an interesting study in which continuous therapy is compared to fixed duration therapy. Although ongoing or continuous therapy (such as with Revlimid maintenance) is known to prolong remissions, there has been a concern or question that drug resistance might emerge and negatively impact response to later therapies. In the important study to be reported by Dr. Antonio Palumbo (Abstract #8515), pooled results for 913 frontline patients from two trials (one lenalidomide (Revlimid) based and the other bortezomib (Velcade) based) show outcomes with (452 patients) and without (461 patients) continuous/ongoing maintenance therapy. All outcomes assessed were superior with the continuous therapy, including a key new end point PFS2, defined as the time from start of treatment to the relapse from second therapy (therapy at time of relapse from the continuous maintenance). The PFS2 was 63 months compared to 47 months for the fixed duration therapy patients (P value = 0.0001).
There are two conclusions from this study: 1) The longer first remission (PFS 1) is not cancelled by a shorter second remission (reflected by PFS 2), which is actually also longer; and 2) PFS 2 is an important new assessment tool.
In another abstract, it is important to note that Health Related Quality of Life (HRQOL) in newly diagnosed patients improved along with better PFS and OS outcomes with lenalidomide (Revlimid) maintenance therapy (Abstract #8516: MM020 [FIRST] trial).
- For smoldering myeloma, the predictive role of Freelite, cytogenetics, gene expressing profiling (GEP) and imaging are assessed in different abstracts, helping refine the potential utility of these techniques. Two follow-up abstracts indicate pomalidomide (Pomalyst) benefit in one case predicting a 14-month added survival benefit and the other showing excellent results in combination with bortezomib (Velcade) plus low-dose dexamethasone.
So, a step at a time we continue to see patient benefits with new therapies and improved ability to diagnose and monitor the disease. We await hearing full details at the final ASCO presentations. Stay tuned: I will include all updates in my post-ASCO report on July 26th.