By Jack Aiello, Myeloma Survivor Diagnosed 1995
This is my third time attending an International Myeloma Workshop (IMW) meeting which is held every 2 years. This 4-day meeting consists of 3200 attendees from 41 countries, mostly hematologists (70%) with smaller numbers of pharma reps (15%), researchers, and nurses who were there to present and learn from 620 submitted abstracts, each one focusing totally on myeloma! Like ASH, there are also exhibitors and posters but the focus is very much on the oral presentations. This 17th IMW meeting contrasts with the first one held in 1987 with 34 attendees (including Drs. Robert Kyle and Brian Durie).
Dr. Richardson shared his perspectives about the IMW meeting. I've included more details on individual sessions and topics below:
Although this was one of the final sessions, I believe it to be quite illustrative of questions we have today about myeloma. For each debate, one myeloma expert takes “Yes” side and another argues for “No”, with each doctor presenting their arguments and then offering rebuttals. Before each debate, the audience is polled and polled again after the debate. I’ll report the questions below and the final debate results, with some discussion.
However, had this question been phrased as “High Risk” smoldering multiple myeloma, I believe the voting would have been reversed. Key unanswered questions include:
The thinking was the KRd induction should be reserved for high risk multiple myeloma patients, whereas VRd should be given to the older population. Key unanswered questions include:
This is an important question being asked in clinical trials now (e.g. S1803) but we really don’t have data yet to tell us that we can stop treatment, even after years of being MRD negative. Using MRD negativity as a clinical trial endpoint was also discussed in the context of earlier FDA new drug approval. Key unanswered questions include:
The primary arguments for limiting duration were an increase of secondary cancers after 2 years and that refractory Revlimid is difficult to treat.
Up front daratumumab either as Dara/Rev/Dex (DRd) or Dara/Rev/Velcade/Dex) (DRVd) has shown benefit except in high risk myeloma.
It was noted that while today it is standard of care today, newer treatment approaches like the Forte trial (KRd x 12 cycles) and quad induction therapies, more MRD negative patients might be seen after induction therapy (the preparatory treatment before transplant). And Dr. Richardson added that long-term MDS and acute myeloid leukemia are possible transplant outcomes. Dr. Bensinger theorized that a CAR-T followed by a RIC (Reduced Intensity Condition “Mini”) Allo might be a reasonable treatment plan.
Dr. Kyle remarked “90% of MGUS patients will die of other causes” so treatment for smoldering myeloma patients is being investigated. The classic definition of smoldering myeloma is an M-protein > 3g/dL and no myeloma defining events. Dr. San Miguel noted “There are 51 clinical trials assessing early treatment in SMM.” Researchers are focusing on high-risk multiple myeloma where the definitions of high-risk vary.
Dr Rajkumar said “High risk smoldering myeloma is whatever factors result in a 50% progression to multiple myeloma within 2 years.” Some doctors look at M-protein and call it high-risk if it’s increasing by more than 10% within 6 mos. Others use the 20-2-20 definition of 20% plasma cell, 2% M-protein, and 20 free light chain (FLC) ratio. Genomic profiling may further improve the definition. Treatments being offered to high risk smoldering myeloma patients include “preventive” regimens such as Rev (+ dex) and “curative” regimens with trials.
IMW provided updates on newly diagnosed transplant eligible myeloma that included KCRd (Myeloma XI trial) and DaraVRd (Griffen trial) as well as added convenience with weekly Kyprolis and subQ Dara. And for patients who are not transplant eligible, RVd is better than Rd, which is better than Vd (except for high-risk patients).
While there are many treatment options, choosing therapy should be guided by:
At the IMW conference, updates and posters included:
Cytogenic/FISH tests are used to look at chromosomal changes but newer tests (GEP, NGS) can assess changes in the DNA and may well be the future, especially if results can be tied to treatment decisions. At IMW, the MMRF CoMMpass study is showing early results of a new high-risk subtype and predictors of early relapse.
MRD continues to be discussed and shown to be excellent for prognostic purposes but not used on any regular basis to guide therapy outside of clinical trials. However, I thought an interesting point was made that the role of maintenance is to sustain MRD-. And maintenance trials at IMW showed that either Revlimid or Velcade or even Kyprolis can be given as effective maintenance.
Beyond what I’ve written, even more was discussed, such as targeting mutations and pathways like RAS (KRAS, NRAS), BRAF, MEK, BCL2 (found in t(11;14) and treated with Venetoclax), and MCL-1. Some drugs already exist for these and are incorporated in the MMRF’s MyDRUG precision medicine trial.
PS. I try to be accurate with my note taking but material is presented quickly. If you have any questions, please feel free to email me email@example.com
about the author
Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can help accelerate a cure by weighing in and participating in clinical research. Founder of HealthTree Foundation (formerly Myeloma Crowd).