There are several wonderful pieces of myeloma-related news this week that deserve to be shared. From Iceland to China, here are the highlights.
Iceland’s iStopMM Project Published in ‘Nature Medicine’
There is great news for the IMF-supported iStopMM (Iceland Screens Treats or Prevents Multiple Myeloma) Project in Iceland which is headed by Principal Investigator Dr. Sigurdur Y. Kristinsson (Professor of Hematology, University of Iceland— Reykjavík, Iceland).
A new report documenting for the first time the prevalence (occurrence) of smoldering myeloma (SMM) in a screened population has just been published in the prestigious monthly journal, Nature Medicine
This is very important for both the iStopMM Project and the myeloma community at large.
As noted by the lead author of the study, Sigrún Thorsteinsdóttir (University of Iceland— Reykjavík, Iceland): “We are proud to report the prevalence of Smoldering Multiple Myeloma (SMM)…Importantly, although two-thirds of the patients have a low-risk of progression to multiple myeloma, we show in this screening study that screening can identify [the remainder or one-third of the] possible candidates for early treatment… [and potential curative approaches].”
Unexpected High Prevalence
A major strength of the iStopMM study is being able to screen over 75,000 individuals of the Icelandic population. The prevalence of SMM was 0.5 percent among those aged 40 years or older—more than what was anticipated. Prevalence increased with age, with 1.1 percent among those aged 70 years or older, and 1.6 percent among those aged 80 years or older. The median age of individuals diagnosed with SMM is 70 years—in line with prior reports.
It is notable that all SMM patients in this screened cohort had > 10 percent plasma cells in the bone marrow. This can be the key indicator of the disease beyond the monoclonal gammopathy of undetermined significance (MGUS) stage—an important finding since there is such discordance in the 20/20/20 and PETHEMA (Programa para el Tratamiento de Hemopatías Malignas) clinical risk models for SMM.
The authors want to emphasize that the iStopMM Project has produced very encouraging results, demonstrating the value of population screening. However, any strong recommendation to implement systematic screening for MGUS and SMM must await the outcomes of the randomized trial that evaluates survival and quality of life.
In addition, we need improved biology-oriented strategies to better assess the risk of progression for individual patients.
Nonetheless, there is great optimism that many new innovative approaches will emerge and lead to enhanced outcomes for screened individuals, especially those with high-risk SMM. As was evident in the reports from ASH, many more projects are ongoing in iStopMM and multiple additional publications are anticipated in the coming months. Exciting times, indeed, for this unique screening project.
China’s CAR T Product (GC012F) Receives FDA Clearance for IND Application
In a press release, Gracell Biotechnologies made a recent important announcement that it has received clearance for its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to commence a Phase 1b/2 clinical trial for the treatment of relapsed refractory multiple myeloma (RRMM).
“GC012F is an autologous CAR-T therapeutic candidate dual-targeting B cell maturation antigen (BCMA) and CD19, and utilizes Gracell's proprietary FasTCAR next-day manufacturing platform… GC012F is currently being studied in multiple investigator-initiated trials (IIT) evaluating its safety and efficacy in RRMM, newly diagnosed multiple myeloma, and B-cell non-Hodgkin's lymphoma. At the European Hematology Association 2022 Hybrid Congress, Gracell presented longer-term follow-up clinical data of GC012F in RRMM that showed a 100% minimal residual disease (MRD) negativity rate in all patients treated,” according to Gracell’s press release.
GC012F is a unique CAR T approach developed and has already been tested in China. It should be noted that GC012F did receive Orphan Drug Designation from the FDA in November 2021.
GC012F simultaneously targets B cell maturation agent (BCMA) and another antigen, CD 19. BCMA is widely expressed on myeloma cells and is targeted by many other immune therapies.
The CD 19 expressed on more immature cells. The hope is that this would encompass cells closer to myeloma stem cells or to the origin of the myeloma clone.
In addition, this autologous CAR T candidate uses FasTCAR— a next-day manufacturing process developed by the company. The rapid availability of this CAR T product is a very exciting development and will speed up access for patients.
The myeloma community became aware of this CAR T therapy at the 2022 American Society of Hematology Annual Meeting which I discussed in my previous blog as well as in the Post-ASH Conference Series. The results of the study in frontline high-risk myeloma patients were presented by Juan Du, MD, PhD, Director of the Department of Hematology, Changzheng Hospital of the Naval Medical University in Shanghai, China. Dr. Juan Du is also an International Myeloma Working Group (IMWG) investigator and a member of the IMF’s Immune Therapies Committee.
The product proved to be well-tolerated among the initial cohort of 17 patients, with 100 percent achieving MRD negativity— a pretty remarkable outcome! This trial continues to expand as the team awaits approval by the FDA in China.
[ UPDATE: On February 13, Gracell Biotechnologies announced through a press release that "the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has cleared Gracell's Investigational New Drug (IND) application for GC012F, an autologous CAR-T therapeutic candidate, for the treatment of relapsed/refractory multiple myeloma (RRMM)." ]
This is an encouraging new CAR T approach. Further developments in both China and the US are eagerly awaited.
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