March 4, 2021

On February 26, the Food and Drug Administration (FDA) approved melphalan flufenamide (Pepaxto®) in combination with dexamethasone for the treatment of relapsed or refractory myeloma in patients who have received at least four lines of prior therapy, including an IMiD, proteasome inhibitor and a CD38-directed monoclonal antibody. 

According to the March 1, 2021 issue of the Journal of Clinical Oncology, Pepaxto® is a next-generation nitrogen mustard agent, a first-in-class agent evaluated in the phase II HORIZON trial. The trial involved 157 patients and resulted in an overall response rate of 29% and PFS (progression-free survival) of 8.5 months in responding patients. The safety profile was acceptable and the conclusion from lead author Dr. Paul Richardson is that Pepaxto is an important new treatment for patients for relapsed or refractory disease. Results are being further evaluated in the OCEAN randomized trial, in which results are compared to pomalidomide plus dexamethasone. 

BOTTOM LINE: It is great to have another option available with a unique new mechanism of action. We look forward to further trials with different combinations in earlier disease settings. 

Published in NEJM: Results of the idecabtagene vicleucel CAR T-therapy trial

On February 28, the results of the phase II ide-cel trial in patients with refractory myeloma were published in the NEJM. In this study patients were treated with T cells (autologous, meaning their own) engineered to target B cell maturation antigen (BCMA) on the surface of the myeloma. Of 140 patients enrolled, 128 received ide-cel treatment. The overall response rate (OR) was 73%, with 33% experiencing complete response (CR) and 26% achieving negative MRD (minimal residual disease) at the 10 to the -5 level. Reduced blood-count levels and cytokine release syndrome (CRS) were the most common toxic effects. However, grade 3 or greater (severe) CRS occurred in only 5% of patients. 

Overall, the results were extremely promising, with a median response duration of 10.7 months, progression-free survival (PFS) of 8.8 months and overall survival of 19.4 months. Patients achieving a complete response or better had a longer response duration of 19 months. 

The good news is that approximately one-third of patients achieved meaningful responses in the one-to-two-year range or better, allowing an excellent quality of life period of time off from any type of conventional anti-myeloma therapy—a major benefit! 

Ide-cel therapy is currently under review at the FDA and recommendations regarding possible official approval will be available later this month.

Other recently published papers 

  • Immune dysregulation in myeloma 
    An excellent review in the journal Blood with Kyehei Nakamura as first author provides an understanding of the complexity and dynamic nature of the immune response in patients with myeloma. The host (or normal) immune system “acts as a rheostat that fine-tunes the balance between dormancy and disease progression,” he writes. Each of the different stromal cells (those surrounding the myeloma in the bone marrow) have unique functions in modulating myeloma cell growth and persistence. 
  • Results of deep MRD profiling 
    An important article with an accompanying editorial in Blood emphasizes the different aspects and significance of MRD testing patients with standard risk versus higher risk myeloma. Achieving a negative MRD status (at the 10 to -5 level or better) is crucial for patients with high-risk disease to maximally improve the chances of a better outcome. Patients with standard risk disease are more likely to achieve an MRD-negative status and benefit from a much-improved outcome in this setting.
  • Treatment recommendations from the IMWG Bone Working Group 
    Earlier in February, the Bone Therapy Recommendations were published in Lancet Oncology This important update includes a discussion of the new agent denosumab, an alternative to bisphosphonates such as Aredia or Zometa. The duration of bone therapies and the role of radiation therapy and surgery are also discussed. 

Bottom line 

It is wonderful to see myeloma research move strongly forward with the approval of another new agent and potential approval of a first CAR T-cell therapy for myeloma in the near future. In the meantime, patients must stay strong and resilient (watch the IMF Living Well webinar on resilience) during this MYELOMA ACTION MONTH

Working to enhance resilience is definitely a key objective these days. “The yearlong crisis has taken at terrible toll on mental health,” writes Melinda Wenner Moyer in the current issue of Scientific American. “Coping methods based in disaster and trauma psychology can help.” Moyer quotes Mana Ali, a psychologist at MedStar Rehabilitation Hospital: “You can feel scared and fearful and angry and resentful and simultaneously be a victor and resilient.” If you are feeling alone, the article suggests, sign up for Caring Calls, a nonprofit service that facilitates weekly phone conversations, by calling (212) 769-2850. 

It is important for patients to get vaccinated for COVID-19 as soon as feasible and to continue wearing a mask and using other precautions. Please note that it is OK to receive whichever vaccine is available first. Getting vaccinated is the key goal!

Be well and stay safe.


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Image of Dr. Brian G.M. DurieDr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.

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