The International Myeloma Working Group (IMWG) convened for its Annual Summit this year from June 7-9, 2022, in Vienna, Austria where more than a hundred IMWG members participated in current discussions that are of greatest importance in myeloma research.
This was the first in-person IMWG Summit in two years—myeloma investigators and partners were very excited to be able to meet and discuss pressing questions face to face this time around.
A degree of normality has returned, and everyone is glad to exclaim, “We’re back!” Every effort was made to achieve the usual schedule while ensuring everyone’s safety from COVID-19. Each participant had to test negative for COVID-19 each day, and masks were required in order to participate in the formal summit meetings. I am very pleased to report that no participant tested positive for COVID-19 during the summit and that everyone was able to proceed safely to the European Hematology Association (EHA) Congress or to wherever their next destination was, after the IMWG Summit.
Additionally, the International Myeloma Foundation (IMF) held its annual awards ceremony on Wednesday, June 8th, for the recipients of this year’s Robert A. Kyle Achievement Award and Brian G.M. Durie Outstanding Achievement Award.
On behalf of the IMF, I would like to warmly congratulate this year's Robert A. Kyle Lifetime Achievement Awardee, Hervé Avet-Loiseau, MD, PhD, (University Hospital Center of Toulouse—Toulouse, France; University Hospital of Nantes—Nantes, France) and Brian G.M. Durie Outstanding Achievement Awardee, Bruno Paiva, PharmD, PhD (CIMA Universidad De Navarra—Pamplona, Spain).
Dr. Avet-Loiseau and Dr. Paiva are truly deserving of these IMF achievement awards, which are presented each year to outstanding individuals who have made significant contributions in the field of myeloma research.
Key Takeaways: A 2022-2026 Perspective
The Summit’s format this year for presentations was considerably shorter, to accommodate more time for an open discussion. This resulted in more active engagement from the audience and many helpful points were discussed. Five plenary topics and four working group Committee reports were presented.
Session 1: Early Disease
Sigurdur Kristinsson, PhD (University of Iceland—Reykjavik, Iceland) did a presentation on “Is Screening the Way to Go?,” summarizing the results of the Black Swan Research Initiative® (BSRI)-supported iStopMM (Iceland Screens, Treats, Or Prevents Multiple Myeloma) Project which screened over 80,000 individuals.
The unexpected finding was that the screening not only identified monoclonal gammopathy of undetermined significance (MGUS), but it also found both smoldering multiple myeloma (SMM) and full-blown myeloma. SMM turned out to be very common—with a prevalence of 0.5% in individuals aged 40 years and older. This means early intervention could be offered to those with high-risk SMM, with excellent outcomes expected—even a cure.
Is screening currently recommended? The consensus is that, although the results look promising, we must await the outcome of the iStopMM randomized trial to be able to assess improvements in overall survival and quality of life. It does seem that screening will be one way forward in 2026.
Bruno Paiva, PharmD, PhD (CIMA Universidad De Navarra—Pamplona, Spain) evaluated if simple precise testing is needed to identify high-risk smoldering multiple myeloma (HR SMM). The answer is yes, with the incorporation of blood testing for the presence of circulating monoclonal plasma cells [myeloma]. With very sensitive testing, it is possible to use a precise cut-off of 0.015%. Less than this identifies patients with a very low likelihood of progression to active myeloma. It is extremely important to exclude patients from unnecessary intervention.
María-Victoria Mateos, MD, PhD (University Hospital of Salamanca—Salamanca, Spain) discussed the results of various treatments for HR SMM. The aggressive CESAR Trial (KRd + ASCT) produced excellent results, with only 3 out of 90 patients having disease progression to active myeloma after an average follow-up of over 4 years.
Is simpler treatment using lenalidomide alone also an option? Early data from an ECOG trial (E3A06) is promising. As pointed out by Dr. S. Vincent Rajkumar (Mayo Clinic—Rochester, MN), it will take a very long follow-up to assess the full impact of treatments for HR SMM. This creates a dilemma for future planning and no consensus solution has been offered so far!
Session 2: Minimal Residual Disease (MRD)
Jesús San Miguel, MD, PhD (Clínica Universidad de Navarra—Pamplona, Spain) chaired the session on assessing the current status of MRD testing.
Alberto Orfao, MD, PhD (University of Salamanca—Salamanca, Spain) noted comparable information achievable, using either NGF or NGS testing methods with negativities at the 10-5 to 10-6 levels being the most important. Perhaps the most important new information is that the NGF (Flow MRD) test has been approved as a test in Europe (IVDD compliant) since Becton Dickinson (BD) took over the original commercial entity Cytognos. This means that NGF can be available at a cost of $100 to $200 which is much more manageable versus $900-$1,000 for NGS (the sequencing method).
Hervé Avet-Loiseau, MD, PhD (University Cancer Center of Toulouse—Toulouse, France) emphasized that the MRD endpoint should be considered as a “stand-alone” indicator to establish the best correlations, especially at the 10-5 to 10-6 levels of sensitivity. He did, however, note that in the CASSIOPEIA Trial, MRD negativity did not indicate a better outcome for patients with high-risk cytogenetics [17p- / t(4;14)].
In his personal presentation, Dr. San Miguel, drew attention to the caution required linked to decisions for individuals identified as MRD-positive versus MRD-negative. Not only are there important technical difficulties which need to be standardized, but low-level MRD positivity can be linked to a good outcome. There is a need to identify such patients perhaps, on the basis of an MGUS-like phenotype on flow testing which indicates a very good prognosis and more importantly, NO need for additional potentially toxic therapy.
Session 3: Frontline Therapy
Dr. S. Vincent Rajkumar (Mayo Clinic—Rochester, MN) reviewed if sufficient data exist to indicate that the use of four drugs (a quadruplet) in the frontline setting is a standard of care (SOC).
Although four drugs such as daratumumab (Dara) or isatuximab (Isa), VRd or VTd clearly produce a longer initial remission (progression-free survival, PFS), longer-term survival data are awaited.
Along the same lines, it was noted that the DETERMINATION Trial was presented as a plenary abstract at the recent ASCO Meeting in Chicago in which Dr. Paul G. Richardson (Dana-Farber Cancer Institute—Boston, MA) discussed that PFS was significantly prolonged after early transplant (versus delayed ASCT), but that overall survival (OS) is not impacted.
Thus, there are pros and cons to more intense initial treatment options—leaving very important considerations open such as patient choice, costs, convenience, and access in many healthcare systems.
Dr. Thierry Facon (Chu De Lille—Lille, France) emphasized that for non-transplant eligible (NTE) patients (especially for the more elderly or frail), the three-drug combination of Dara Rd (the so-called MAIA regimen) is very effective and well-tolerated and perhaps, sufficient for the time being.
Other discussants: Tom Martin, MD (University of California San Francisco—San Francisco, CA) Yi Lin, MD, PhD (Mayo Clinic—Rochester, MN); Dr. Richardson and Prof. Mario Boccadoro (University of Turin—Turin, Italy) made additional important comments.
First, the early introduction of CAR T-cell therapy and/or the use of bispecific antibodies may really improve both PFS and overall survival, if introduced early. Although this may be true, many cautions were raised in terms of access, potential toxicities, and costs.
Overall, there was a sense we need to await the outcomes of trials such as CARTITUDE-5 and CARTITUDE-6 evaluating CAR T therapy in the transplant-eligible (TE) and non-transplant-eligible (NTE) settings.
Session 4: Early Relapse
This session, led by Philippe Moreau, MD, PhD (Nantes University Hospital—Nantes, France), evaluated the impact of earlier use of important agents such as anti-CD38 monoclonal antibodies (Dara or Isa). Choices include and it seems will continue to include combinations with IMiDs, such as pomalidomide (for example pomalidomide + belantamab), bispecific monoclonals, as well as a range of new novel agents.
Session 5: Later Relapse
This session, led by Nikhil Munshi, MD (Dana-Farber Cancer Institute—Boston, MA) includes a future look by Kenneth Anderson, MD (Dana-Farber Cancer Institute—Boston, MA). An evaluation of how to include a broader range of patients in clinical trials (at later relapse stages) and a summary of the new IMWG initiatives to establish an immune therapy database and a virtual tissue biobank.
With a future-oriented perspective, Dr. Anderson emphasized the need to understand and treat immune defects in myeloma patients to have a chance to re-establish long-term disease control or cure.
There was a consensus that these types of immune approaches will be crucial to achieving better, longer-term outcomes. There was also tremendous enthusiasm about the immune therapy database and virtual biobank which will provide collaborative opportunities and improve our understanding towards achieving next-generation treatment choices.
Just some brief comments:
- Smoldering myeloma and immune therapies have already been well-discussed
- Bone disease: an important new innovation was the plan to establish a virtual computer database for imaging studies, to be based at Roswell Park Comprehensive Cancer Center in Buffalo, NY. This can be an important step.
- Mass Spectrometry: an important project is to better understand the meaning or significance of low-level spikes detected by very sensitive MS technology. It is likely that many low-level spikes are transient and a normal immune response to infections, but comprehensive studies are required and are already planned. Clearly, MS can detect and track, and at very low levels, know monoclonal myeloma proteins which is a major step forward. We eagerly await a fully commercialized MS product.
Hopefully, this gives flavor to what was an intense but extremely productive 13th IMWG Summit.