International Myeloma Working Group Summit
A summary report from the 2021 IMWG annual meeting which took place virtually.
The IMWG convened virtually for its Annual Summit on June 22-23, 2021. More than 100 IMWG members were invited to join an online platform that supported optimal participation in current discussions of greatest importance in myeloma. Experts in the myeloma field led discussions on the 2/20/20 risk stratification model for high-risk smoldering multiple myeloma, four-drug combination therapies, minimal residual disease as a surrogate endpoint, immunotherapies and the IMF's immune therapy registry, the IMF's virtual tissue biobank, and more.
The Chairpersons of the IMWG Summit
Dr. Brian G.M. Durie
IMF Chairman of the Board and Chief Scientific Officer
Dr. S. Vincent Rajkumar
Mayo Clinic – Rochester, MN
The IMWG Summit Co-leaders
Dr. Jesús San Miguel
Clínica Universidad de Navarra — Navarra, Spain
Dr. Philippe Moreau
University Hospital Hotel Dieu — Nantes, France
Dr. Nikhil Munshi
Dana-Farber Cancer Institute — Boston, MA
The first session was led by Dr. Shaji Kumar (Mayo Clinic — Rochester, MN) — a discussion of the 2/20/20 risk stratification model for high-risk smoldering multiple myeloma (HRSMM). This important advancement came because of an IMWG research project and was published in Blood Cancer Journal in October 2020.
2/20/20 risk stratification model
To find out which patients have progressed and which have not, data was collected from several international sites. The 2/20/20 system was a team effort between Dr. Kumar and Dr. Durie along with the Spanish team — led by Dr. Jesus San-Miguel (Clinica Universidad de Navarra — Navarra, Spain) and Dr. María-Victoria Mateos (University of Salamanca — Salamanca, Spain). The 2/20/20 risk stratification model can predict the development of HRSMM to active myeloma.
The IMWG also produced a point-scoring system and an online calculator app to identify ultra-high-risk SMM (Smoldering Multiple Myeloma) — a group for which immediate treatment can be strongly taken into consideration. Patients who score 12 or more points have ultra-high-risk SMM and qualify for treatment.
The discussion of 4-drug vs 3-drug combination therapies was led by Dr. Philippe Moreau (University Hospital — Nantes, France). Outcomes from the CASSIOPEIA study (D-VTd vs. VTd) as well as the GRIFFIN study (D-VRd vs VRd) made it clear that 4-drug therapies are doing far better than 3-drug therapies.
Early vs. delayed autologous stem cell transplant
Dr. S. Vincent Rajkumar (Mayo Clinic — Rochester, MN) did a presentation on early vs. delayed autologous stem cell transplant (ASCT). While remissions are longer with early ASCT (as shown by the outcome of the French IFM study of VRd with/without transplant), overall survival of patients who delayed ASCT are about the same as those who had early ASCT — therefore, patients who opt for a later transplant or other therapies can still catch up. With the earlier use of CAR T-cell therapy or other immunotherapies as a consolidation approach, this may be the best time to re-evaluate the role of ASCT in myeloma more closely.
However, it may likely take longer than 20 years to justify the value of 3-drug or 4-drug combinations or other aggressive approaches to achieve long-term, disease-free remission or cure.
Dr. Bruno Paiva (Universidad de Navarra — Navarra, Spain) addressed the standardization of MRD testing in clinical trials. Continuous MRD negativity during remission is an excellent measure of long-term benefit. Thus, the importance of MRD in prognosis is highly valued. Discussions about the ideal protocol to assess and demonstrate MRD-negativity as a great alternative to indicate treatment benefit instead of progression-free survival (PFS) are ongoing. The IMF’s Black Swan Research Initiative® is currently investigating even higher MRD sensitivity.
Discussions on current and next-generation CAR T cells and other cellular therapies, such as bispecifics, were led by Drs. Nikhil Munshi (Dana-Farber Cancer Institute — Boston, MA), Tom Martin (UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, CA), and Yi Lin (Mayo Clinic — Rochester, MN).
With CARTITUDE protocol, deep responses to CAR T-cell therapy are up to more than 90 percent, with sustained responses for those having the deepest responses. However, there are concerns about early cytokine release syndrome (CRS) and neurotoxicity among some patients in the trial. An important question about the availability of CAR T-cell therapy in the community setting was raised — it remains unclear how patients will have access to specialized centers at this time.
The role of bispecific antibodies was also tackled in a detailed discussion and took a closer look at exciting data showing several bispecifics to be very active. But toxicities are still a cause of concern — some bispecific products have been taken out of clinical trials because of neurotoxicity.
However, several studies involving teclistamab (a bispecific antibody which targets both B-cell maturation antigen/BCMA and CD3) have gotten excellent responses and are moving forward.
Unlike the “one and done” approach of CAR T-cell therapy, bispecifics therapy is high-intensity and ongoing, which can be tough on patients. There are discussions about limiting the length of treatment with bispecifics (for example, to 6 months or so) and about newer and next-generation products that are non-BCMA targeted.
Drs. Tom Martin and Yi Lin presented a report on the IMWG Immune Therapy Committee, sharing exciting news on major projects. A framework for a new IMWG Immune Therapies Registry has been established by the Committee, to be housed at UCSF, which will collect data on patients receiving the new immune therapies that are used in succession (including those with BCMA as a target, the anti-BCMA CAR T-cell therapies, and the bispecific antibodies currently in clinical trials). The Immune Therapies Registry will become increasingly important in the coming years, as more agents receive FDA approval.
As part of the Asian Myeloma Network (AMN) — an IMF research division and clinical trials group — a Virtual Tissue Bank is currently being developed. Dr. Wee Joo Chng (Cancer Science Institute of Singapore — Singapore) set up a system which standardizes tissue collection — participating centers can retain tissue samples at their sites. Collaboration through information sharing and analyses will be able to measure the efficacies and toxicities that occur in immune therapies.
The Mass Spectrometry Committee was represented by Dr. David Murray (Mayo Clinic — Rochester, MN) and IMF Chairman of the Board Dr. Brian G.M. Durie. The hope is that mass spectrometry or other innovative testing can become a reliable indicator of potential early relapse. Tiny monoclonal proteins can be detected by mass spectrometry at a very early time point. As many as 30 percent of these “tiny spikes” can disappear over time, triggered by infection or some other immune reaction. Topics of the discussion included best implementation of mass spectrometry, how to make it routinely available, and how to interpret the results and detect early relapse.
The Summit Keynote Lecture on the role of COVID-19 vaccination for myeloma patients was delivered by Dr. Evangelos Terpos (Department of Clinical Therapeutics, University of Athens, School of Medicine — Athens, Greece). Unfortunately, vaccination does not produce the levels of neutralizing antibodies that we’d like to see.
There was much disappointment in learning that some of the newer immune therapies (such as anti-CD38 and anti-BCMA products) impaired neutralizing antibody responses required for immunity against COVID-19. Considerations for third “booster” shots were discussed for at-risk patients who are on such therapies and/or who have low blood-lymphocyte levels, which is another risk factor.
A study that will assess booster shots will begin shortly in Greece. Another potential study will include the use of monoclonal antibodies against COVID-19 as early intervention (such as Regeneron, which is available in the U.S.) or even a preventive approach for those who are considered at highest risk of COVID-19 complications.
Dr. Morie Gertz (Mayo Clinic — Rochester, MN) raised the question of how to manage relapsing patients in the real-world setting. Most patients with advanced disease are not eligible for clinical trials because their health status needs to be good to assess potential toxicities of drugs or drug combinations. Early and careful testing of new agents is required for safety reasons, but next-level studies can explore more challenging situations (such as patients with exceptionally low blood-count levels or have compromised kidney or liver function).
The IMWG researchers are also greatly interested in addressing disparities in access to clinical trials as well as accruals. There is a major drive to improve access for all disadvantaged groups.
To help address key clinical trial issues, IMWG researchers and the IMF’s industry partners suggested inviting representatives from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to future meetings. More real-world data analyses will also be incorporated, including quality of life assessments. From these, better priorities can be established when it comes to drug selection and the creation of optimal doses and schedules for emerging agents and combinations.
Other highlights of the 2021 IMWG Annual Summit
Other highlights of the Summit include the presentation of the IMF’s 20th Annual Robert A. Kyle Lifetime Achievement Award to Dr. Nikhil Munshi, the Kraft Family Chair and Professor of Medicine at the Harvard Medical School and the Director of Basic and Correlative Science, and the Associate Director of the Jerome Lipper Myeloma Center at the Dana-Farber Cancer Institute in Boston, MA. This award honors an individual whose body of work has made significant contributions to myeloma research and patient care.
The Brian G.M. Durie Outstanding Achievement Award, recognizing excellence in myeloma research, was awarded to Dr. Shaji Kumar — a consultant in the Division of Hematology and the Mark and Judy Mullins Professor of Hematological Malignancies at Mayo Clinic in Rochester, MN. Dr. Kumar is also the Chair of the Myeloma, Amyloidosis, and an Associate Chair for research in the Department of Medicine at Mayo Clinic.
The 2021 IMWG Summit was a wonderfully successful and productive event with lively interactions among participants who took full advantage of the opportunities to make plans for future research collaborations. It was clear that everyone is looking forward to getting back to an in-person program in 2022!