List of top 10 plasma cell dyscrasia ASH23 abstracts by Manni Mohyuddin

Manni Mohyuddin, Assistant Professor at the Huntsman Cancer Institute at the University of Utah, shared on X/Twitter:

”List of top 10 plasma cell dyscrasia ASH23 abstracts. List may reflect positive/negative studies, but all have influenced thinking. I will summarize each study with teaching point. If you are wondering if there are any practice changing myeloma studies- IMO answer is NO.

Lets start!

1. The definitions of normal versus abnormal light chain levels have changed, and many patients who would previously be called as light chain MGUS now have light chains within normal limits. Excellent practice changing iStopMM (Iceland screens, treats or prevents multiple myeloma) study.

2.In the real-world setting, the performance of dara-len-dex is much poorer compared to the MAIA trial. At 2 yrs of follow-up, only 60% of patients remain on DRd  (This is NOT a 5+ year PFS that we saw in the MAIA trial).

3. In an older, transplant ineligible (based on age) population, Dara-KRd increased rate of MRD negativity (an endpoint of debatable clinical significance in older population), but overall survival was poorer because of high treatment related mortality. If anything- makes a compelling case against indiscriminate use of quads, perils of a single timepoint of MRD as a primary endpoint (and the sheer disconnect with OS) and highlights importance of randomization to see a mortality signal. Much more cardio tox too. For the article click here.

4. Pom/Cy/Dex beats Pom/Dex in a Phase 3 study-PFS- 10.9 versus 5.8 months. Useful all-oral regimen-and highlights how cyclophosphamide remains an under-rated but important part of treatment regimen. Doubt melflufen or selinexor would do better. For the article click here.

5. In a RCT that assessed a single-timepoint of MRD negativity (a questionable endpoint), a 4 drug combo of Isa-KRd beat KRd, but led to 4x higher treatment related deaths. Unclear if this makes a convincing case for quads for all-comers, without better long-term data. Trial aimed to answer a triviality (at least today)- 4 drugs obviously would lead to better MRD negativity. No equipoise anymore for 4 versus 3 when endpoint is MRD negativity- answer obvious. Longer-term answers of PFS and OS remain unknown. For the article click here.

6. Long-term data of ide-cel from KARMMA-3 continues to underwhelm- but overall survival data missing in the abstract. Considering that an FDA ODAC meeting has been called to discuss this, I worry regarding what the overall survival data shows.

7. Patients who progress on up-front quad therapy have poor outcomes- a median overall survival of 6-12 months. These are patients in need for novel therapies soon- and have very poor outcomes with whatever is given after progression on quad. For the article click here.

8. In a small randomized study (very underpowered for formal comparisons) for 11;14, dara/ven/dex led to 33 month PFS of 73% versus 38% with dara/velcade/dex, with 38% MRD negativity rates at 10-5. Tons of caveats, but data holds promise.

9. Extremely intensive therapy with DKRd, transplant, more DKRd, a second transplant and Dara-Len for high-risk myeloma was associated with a rather high-rate of study discontinuation, treatment failures, and (still some) early progressions. Although the 2 year PFS is 87%, I think similar results could have been achieved with much less intense therapy. More work needs to be done to find ideal approach for these patients. For the article click here.

10. The death of salvage auto? The only RCT done on this shows no efficacy of salvage transplant compared to just continuing therapy. Vast majority of patients not even exposed to lenalidomide- so don’t know how this extrapolates- but sobering data.

Thanks for reading! END.”

Source: Manni Mohyuddin/Twitter