ASCO 2018: Helpful Guidance, But No Breakthroughs
May 17, 2018
ASCO 2018: Helpful Guidance, But No BreakthroughsWRITTEN BY: Brian GM Durie MD
The abstracts for the 2018 American Society of Clinical Oncology (ASCO) annual meeting next month have just been released. Among the 7 oral presentations, 62 posters, and educational sessions focusing on multiple myeloma, no dramatic new findings are reported. But there are several important updates and helpful discussions to guide practicing clinicians and inform patients.
Perhaps the most important updates are found in abstracts #8008 (oral), #8010 (poster) and #8021 (poster), which present and review immune-related adverse events (irAEs) and responses in trials combining the checkpoint inhibitor pembrolizumab with pomalidomide (KEYNOTE183) and with lenalidomide (KEYNOTE185). In the FDA analysis (abstract #8008), the increased death rates with the combinations are summarized. The individual trial results include details of the unexpected irAEs, with emphasis on four pembrolizumab-related deaths in the study with lenalidomide (one cardiac arrest, one cardiac failure, one myocarditis, and one pneumonia) and four treatment-related deaths (two linked to pembrolizumab) in the study with pomalidomide (one myocarditis, one Stevens Johnson Syndrome—a severe allergic reaction that affects the skin). The summary is that there is a highly unfavorable benefit-risk profile for these combinations, which are no longer recommended.
On a more positive note, the initial results of the ARROW trial (abstract #8000) are reported by Dr. María-Victoria Mateos from Salamanca, Spain. In this trial, once weekly Kyprolis/dexamethasone (Kd) using a dosage up to 70 mg/m2 proved to be superior and with equivalent toxicities versus the standard twice-weekly dosing schedule (20/27 mg/ m2). It is definitely helpful to know that this more convenient, once-weekly schedule is effective in the relapsed/refractory setting.
Other positive results include those with daratumumab (abstracts #8002, #8058, #8011 and e20005). Results with the combination of daratumumab plus Kyprolis/dexamethasone (Kd) weekly (#8002) are promising, and the combination is well tolerated. Two abstracts summarize daratumumab administered by the subcutaneous route (#8058 and #8011), with limited data available thus far. An important clinical note (e20005) is the increased occurrence of upper respiratory infections and pneumonia in patients receiving daratumumab treatment. Certainly important to be aware of!
CAR T-therapy data
Two abstracts (#8007 and #8024) focus on follow-up data with bb2121 anti-BCMA CAR T therapy, earlier results having been presented at the ASH 2017 meeting. Not much new is presented in abstract #8007, with early results in 21 treated patients, of which 18 were evaluable. Responses continue to be promising.
A fuller analysis of depth of response with MRD testing in the bb2121 trial is provided in abstract #8024. Nine of ten evaluable patients are noted to be MRD negative. However, of these, 1 was at the 10-4 level, 6 were at the 10-5 level, and 2 were at the important, deep-response level of 10-6 (negative at 1/million level), which is predictive of more sustained MRD negativity. Strangely, this group of patients had very mixed traditional response levels: 2 stable disease, 3 PR, 2 VGPR, 2 CR or sCR. These data are hard to reconcile with the MRD results, and there will surely be keen interest in evaluating all details at the ASCO meeting next month, when more follow-up information will be available.
Results with the combination of venetoclax plus Kd are presented in abstract #8004 and continue to look promising, as do results with PVd (pomalidomide, Velcade® [bortezomib], and dexamethasone) in abstract #8001. Selinexor®, Velcade, and dexamethasone (SVd) (abstract #8056) is also a promising combination in RRMM, as has been previously reported, as is the isatuximab, pomalidomide, and dexamethasone combination, for which results in a phase Ib trial in RRMM (abstract #8038) are presented.
A wide range of topics are covered in the 2018 Educational sessions, as well as the Discussion and Meet the Professor sessions. Attendees will have access to many prominent experts in the field. Particularly interesting topics include “CAR T and Cellular Therapy” presentations; “Outcome Disparities in African Americans”; “Is Skeletal Survey Evaluation in Myeloma Dead?”; “Should Everyone Receive Monoclonal Antibody Therapy in First Relapse (Yes or No)?”; and a highly anticipated debate between Dr. Vincent Rajkumar and Dr. Rafael Fonseca on “The Value and Cost of Myeloma Therapy—Can We Afford It? (Yes or No).”
The topic of value and cost is very much in the news. A major concern is that few if any realistic solutions to the problem of high drug costs are being offered. It is therefore of particular note that new solutions discussed in the May 17, 2018 New England Journal of Medicine may, in fact, gain some traction as viable options. Primary among them is the suggestion to establish a nonprofit manufacturer for generic drugs. A consortium of hospitals is already following this approach. In this high-stakes arena, where many options can succeed over time, it is very hard to predict which will work best. All we know is that high prices both restrict access and severely burden an already overwhelmed heath delivery system.
A look ahead
We look forward to the expanded data that will be presented during the ASCO meeting, June 1-5, in Chicago. Full details of the most important myeloma studies from ASCO will be discussed during the IMWG Conference Series, which will air live online on June 13 from the IMWG Summit in Stockholm (check back here for details). Our Conference Series broadcast will also incorporate data that will be presented at the 2018 European Hematology Association Annual Meeting in June.
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