Editor’s note: This blog was originally published by Jack Aiello on the International Myeloma Foundation’s website.
Today’s events began with 9:30 a.m. education program on 1) managing Newly Diagnosed High-Risk (HR) Multiple Myeloma patients 2) Sequencing treatments, and 3) the role of stem cell transplant (SCT) and maintenance. Dr Angela Dispenzieri spoke on the first topic, and she reminded the audience that “High-Risk” doesn’t just mean cytogenetic factors like del(17p), but also patient frailty or a patient’s access to and the cost of drugs must be considered. She also reminded folks that the ISS staging using albumin and beta 2 was revised, denoted as R-ISS, to include serum lactate dehydrogenase (LDH) and cytogenetic HR factors that make up much of stage 3. Now, multiple myeloma patients in stage 1 = 28%, 2 = 62% and 3 = 10%. And prognostic 5 year OS rates for stages 1-3 are 81%, 60%, and 40%, respectively, which explains why there’s a significant effort to determine better treatments for stage 3 patients. Evidence shows that HR patient should be treated with Velcade®-based regimens at induction, consolidation, and maintenance.
Dr. Noopur Raje (SF Support Group folks will know her because she spoke at our past Oct ’16 support group meeting) tackled the second topic. She stated that treatment goals should always be to obtain good and deep responses while maintaining/improving quality of life. Should MRD- be a goal? Yes, because it translates into better progression free survival (PFS) and overall survival (OS). However, she said, “Not all patients will obtain a Complete Response (CR) and MRD-, and this needs to be considered.” Relapsed/refractory MM patients need to assess past treatments and responses before selecting future treatments. Should everyone get an MRD test? The panel of experts suggested that this isn’t ready for “prime-time” yet, but rather should be done within a clinical trial.
Finally, Dr. Philip McCarthy spoke about transplants, beginning with “Every 5 years folks ask if the SCT is dead. But it isn’t…not yet.” He proceeded to show many trial results displaying PFS and OS benefits with transplant as well as maintenance.
Next, I attended some oral presentations that provide some provocative information: 1) Using flow cytometry may represent a better way to classify HR SMM (Abstract #373); 2). Next generation sequencing can produce more accurate results than FISH when classifying HR MM patients (Abstract #374); 3) For those with Light Chain Myeloma, the serum free light chain tests offer improved sensitivity and better correlation with clinical outcomes than does the 24 HR urine assessment (Abstract #376). That last one provides the patient both benefit and ease of FLC test instead of a urine collection…a real winner.
In the middle of the afternoon, I had a great meeting with folks at Sanofi. If you’ve had a transplant, you may well have used the Sanofi drug called Mobilzil which mobilizes your stem cells from your marrow into your blood stream for harvest. But I also picked up a flyer that shows Sanofi beginning a randomized phase 3 trial with Isatuximab (CD38 mAb) +/- Pom & dex for RR MM patients. All the drug costs are being covered by Sanofi so in addition to being closely monitored by your oncologist, there’s no drug costs. In the Bay Area, we’re quite familiar with Isatuximab because UCSF has conducted several earlier trials with this drug, previously known as SAR650984. Down the road it will be interesting to see how this drug compares with the other CD38 mAb Darzalex® (Daratumumab).
The afternoon ended with more oral presentations, this time on new therapies: 1) Nelfinavir is an old, generic oral drug that the FDA approved as an HIV protease inhibitor. A group in Switzerland has shown that when combined with Velcade and dex (NVd) and given to Velcade-refractory patients, ORR was 65% (Abstract #487); 2) Venetoclax (BCL-2 inhibitor) has single agent activity for MM patient but in particular has an ORR of 40% in patients with t(11:14) (Abstract #488); 3) Selinexor (XPO1 inhibitor) plus low-dose dex (Sd) shows about a 20% ORR for patients refractory to Rev, Velcade, Pom, and Cfz (“quad-refractory”) and even Dara (“penta-refractory”) (Abstract #491). The exciting thing about all 3 of these drugs is that they represent different mechanisms of action than we have in today’s therapy arsenal. However, it’s important to note that these were all small trials (20-70 pts) and all drugs had some significant, but hopefully manageable, side effects. Finally, Pembrolizomib (checkpoint inhibitor) with Pom-dex for RR MM pts showed ORR in 65% of patients, but it too, also had side effects that required half the patients to dose-reduce (Abstract #490).
Finally, poster #3558 caught my attention “Real-World Trends in Treatment Use, Healthcare Costs, and Overall Survival Among Patients with Multiple Myeloma.” One of the conclusions states that total healthcare costs have risen steadily since 2000. However, drug costs increased slower than other cost components and remained a minority of the costs.
On that note, it’s been a long day and tomorrow’s first oral presentation is at 7 a.m.