December 4, 2018
Before presenting my ASH summary, I’ll mention a late-breaking abstract presentation that I was unable to attend early this morning focused on a phase III trial using Darzalex (daratumumab) in front-line therapy plus Rev-dex versus Rev-dex only for transplant-ineligible patients. The abstract # LBA-2 showed that the addition of Dara decreased the risk of progression and death by 45%. In this interim analysis of 737 patients, median progression-free survival (PFS) for the Rd was 32 months while the D-Rd arm mPFS had not yet been reached. Although one cannot compare trials, PFS improvement for Dara-Rd over Rd is similar to VRd over Rd. In addition, Dara-Rd CR responses were deeper than Rd with CR of 48% vs 25%. In summary, we may see Dara being used more in induction therapy.
Here’s my preliminary summary of ASH 2018, and I emphasize “preliminary” because I’ll be learning more about the interpretation ASH 2018 results as I listen to follow-up presentations by MM expert oncologists over the next 1-2 months.
Induction: In addition to the aforementioned D-Rd, early trial results were also presented using Dara-VRd and Dara-CyBorD in newly diagnosed patients. Will standard induction become a four-drug regimen one day?
Maintenance: Ninlaro (ixazomib) was shown to have improvement over no maintenance after a transplant. So for those 30% of patients unable to take or continue on Revlimid maintenance, Ninlaro can be considered.
Relapsed/Refractory: Longer follow-up for Pollux (Dara-Rd) and Castor (Dara-Vd) continued to show efficacy for relapsed/refractory multiple myeloma patients. Other regimens for these patients include Vel-Pom-dex, Cfz-Rev-dex, Cfz-Elo-dex, and more.
- CAR-T therapy: Many different CAR-T programs were presented but the numbers are still small. We still need results from more patients, a better understand of response measurement tools (for example, perhaps CAR-T cell persistence/longevity is better than minimal residual disease (MRD), and longer term results.
- New Drugs: Selinexor demonstrated good responses in penta-refractory patients and will likely be the next new drug approved for this category of pt. Melflufen (a unique alkylating agent) also showed good responses for pts who are refractory to 3 other categories of drugs. Isatuximab and Venetoclax showed promising results. A BITE AMG420 shows initial promised but the delivery system of 4 weeks continuous infusion needs work.
- There was considerable focus on high-risk multiple myeloma as well as unfit & frail MM patients, both groups having unique needs.
Wishing you the best of health!