Day 2 ASH: Transplant is still a promising treatment, but MRD is King

Jack Aiello |

Today began with watching ASH abstract presentations from yesterday.  This is actually one of the benefits of attending the meeting virtually. Presentations are often scheduled at the same time and at the in-person meeting, you need to make a decision which to attend.  But being virtual, I’m able to watch a replay of a session I missed yesterday that focused on transplants.

Perhaps the most important presentation reviewed the IFM2009 trial after nearly 8 years of follow-up.  This trial tries to answer the question “To transplant or not (or at least delay)?”, given we have newer drugs.  Specifically, 700 newly diagnosed patients after getting Rev-Vel-dex induction were randomized to either get a transplant or additional cycles of RVd.  And then everyone would get a year of Rev maintenance. One important note: If you were in the non-transplant arm and relapsed, you could “cross-over” and get a transplant, since everyone’s stems cells were harvested at the beginning of the trial.

The results were presented in abstract 143, the abstract number.  While there was initially a progression-free survival (PFS) benefit, after 8 years, there was still no Overall Survival (OS) benefit. Rather, the benefit was seen in patients who achieve MRD-negativity, no matter how you got there, transplant up-front, delayed, or none at all.  One thought is that if patients achieve MRD-negative after induction, perhaps that might be used to identify patients who don’t need a transplant. And remember, even though OS was the same for up-front vs delay transplant, a patient is typically able to handle a transplant earlier than when they’re older. However, there’s more. The U.S. (Dana-Farber Cancer Institute — Boston) also participated in this trial, adding another 700 patients, with one big difference: maintenance treatment was given till progression rather than the one-year fixed timeframe. Will this make a difference?  We don’t know yet because the US got a later start and patient follow-up is shorter. My personal conclusion is that MRD, specifically depth of response, is what matters and getting a transplant can help achieve that goal for most patients.

Other transplant abstracts showed: 1) In the Forte trial which originally showed similar responses between KRd_SCT and KRd_12 cycles, longer follow-up shows the transplant arm shows improvements in both 45 mos MRD (10-5) and 3yr PFS…68% vs 54% and 78% vs 66% respectively [141]; and 2) The all-oral regimen (except SCT) of Ixa-Rev-dex followed by SCT followed by IRd consolidation followed by Rev for Standard risk and IxaRev for High Risk resulted in good efficacy with limited follow-up (13 mos).

Here are a few of the studies presented today, all for relapsed/refractory multiple myeloma patients:

  • Apollo, phase III, DaraSubQ+Pom+d vs Pom+d resulting in benefit for both 12mos PFS (52% vs 35%) and OS (69% vs 44%) [412]
  • Phase II, Dara+Cytoxin+dex+Pom vs Dara+Cytoxin+dex showed advantages in the Pom arm among ORR, PFS, and OS. In addition, if a patient progressed on the Dara+Cytoxin+dex, adding Pom helped many patients. [413]
  • Ikema, Isatuximab+Cfz+dex vs Cfz+dex showed depth of response improvement in the Isa-Kd arm, and while follow-up is too short, median PFS is expected to exceed 30 mos. A few Dara-exposed patients but not refractory are part of this trial. [414]
  • KyCydex vs Kydex showed particular PFS benefit for the Rev-refractory patients (26 vs 9 mos). [415]
  • ANCHOR, A phase 1/2a trial examining 2 treatment regimens: Melflufen+dex combined with either Dara (33 patients) or Vel (13 patients). Melflufen RP2D (Recommended Phase 2 Dosage) will be 30mg for the Dara arm and has not yet been determined for the Velcade arm. Both arms showed ORR of 73% and 60% respectively and the med PFS for the Dara arm was 13 mos. [417]

One other study I want to mention is abstract [437], which focused on Quality-of-Life results over the first 15 months post CAR-T treatment of the Ide-cel (bb2121) platform. The results showed that Ide-cel resulted in meaningful QoL benefits. It’s important to understand that many trials these days include an analysis of Patient Reported Outcomes (PRO’s) which is valuable to all future patients.

That’s it for tonight. Tomorrow’s first meeting starts at 7:00 a.m., and they run through mid-afternoon. And then on Tuesday morning at 8:00 a.m., patients, caregivers, and doctors around the world can view the IMF’s popular livestream IMWG Conference Series from ASH 2020. IMF Chairman Dr. Brian G.M. Durie, Dr. Joseph Mikhael, IMF Chief Medical Officer, Dr. Maria V. Mateos, and Dr. Thomas Martin distill, debate, and discuss the latest news and trends in the treatment of multiple myeloma from the 62nd Annual ASH Meeting. If you haven’t already done so, you should register at: https://www.myeloma.org/videos/imwg-conference-series-ash-2020

Be your own best patient advocate.

— Jack Aiello, on Twitter @JackMAiello

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