Challenges in Treating Relapsed/Refractory Multiple Myeloma

Dietmar Berger, Global Head of Development, Sanofi
Sponsored Content by Sanofi
Published: Sunday, Dec 01, 2019

Dietmar Berger, Global Head of Development, Sanofi

Dietmar Berger
Global Head of Development, Sanofi

Multiple myeloma (MM) poses a high burden for more than 138,000 patients and their caregivers around the world each year.1,2 Myeloma is an incurable disease with patients continuing to relapse over time, becoming more difficult to treat with subsequent relapses.3,4 While considered a rare disease, MM is the second most common hematologic malignancy.1 The median age for MM diagnosis is 69 years old, while five-year survival rates range from 71.7% in patients under 50 years of age to 32.9% in patients over 75 years of age.5

In relapsed MM, the cancer returns after treatment, or after a period of remission. Refractory multiple myeloma refers to cancer that is not responding to standard therapy. There are many potential mechanisms that may impact and promote treatment resistance. Clonal evolution of MM cells and bone marrow microenvironment changes are possible contributing factors.6 In addition, patient-specific characteristics, such as older age,7 high-risk cytogenetics,8 and co-morbidities, including renal impairment,9 also impact outcomes.

Living with relapsed/refractory multiple myeloma (RRMM) can take a significant physical and emotional toll on patients, families and the people who help care for them. Patients’ quality of life is often influenced by the balance between disease-related symptoms, treatment-related toxicity, and treatment response.10

Patients living with RRMM have immense unmet medical needs, as poorer outcomes are seen through subsequent lines of therapy.11 There is an urgent need for highly effective and tolerable treatment combinations to break this cycle and help those struggling with this cancer live as normal a life as possible.

Breaking Down Barriers to Better Care

RRMM is a complex disease. It continuously evolves throughout lines of treatment,12 which means the treatment paradigm must also continue to shift in order to overcome resistance. As the scientific community gains a deeper understanding of disease biology, treatment choices are evolving. Unfortunately, this also means that RRMM patients can face a difficult decision-making process at every phase of their disease.13

While drug resistance is still a major barrier in RRMM, there is hope on the horizon. Significant advancements in treatment – including immunomodulating agents, proteasome inhibitors and, more recently, monoclonal antibodies (mAbs) targeting CD38 – all have the potential to change the outlook for patients in terms of improved outcomes, survival, and quality of life, including heavily pre-treated patients with RRMM.

CD38 is a cell surface protein highly and uniformly expressed on multiple myeloma cells and is a receptor target for antibody-based therapeutics for MM and other cancers. Sanofi’s mAb research focuses on uniquely and directly targeting a specific epitope on the CD38 receptor that is believed to promote programmed tumor cell death (apoptosis).

Researchers at Sanofi have found that bridging myeloma cells with immune cells produced three modes of innate immunity: antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP), as well as directly inducing target cell killing through apoptotic mechanisms without the need for cross-linking. In the absence of cross-linking agents or effector cells, the CD38 mAb specifically induced homotypic aggregation-associated cell death in MM cells.14

Due to the intricate nature of RRMM treatment, further research is needed. Ongoing development must take into consideration some of the realities that patients with difficult-to-treat RRMM face: these are often older or elderly patients, patients may have history of chronic obstructive pulmonary disease or asthma, or living with significant renal dysfunction, or patients may be in fragile or frail health. It is a priority for Sanofi to have Phase 3 research in RRMM as reflective of real-world practice as possible. The research behind the treatment of RRMM has become drastically more sophisticated during the course of my time in the field, and I look forward to seeing its impact on patients living with RRMM.

Continued Commitment to Better Care

At Sanofi, we are working on behalf of RRMM patients and caregivers who face the constant challenges this complex cancer presents.15 We are determined to provide better treatment options through a commitment to drug discovery and development that is rooted in advanced disease understanding and driven by innovative science and technologies.

As part of our focus on malignant blood disorders, we are researching therapeutic options for patients with RRMM specifically, including an in-depth exploration of the potential of anti-CD38 treatments to reduce the progression of the disease.

With our research into CD38 and other investigational MM treatments, we are building on our rich legacy in oncology and pipeline of potential therapies to make a meaningful difference where it’s needed most. We are determined to not only understand but overcome MM, and to support patients living with this challenging disease – and our commitment to this ambition drives our work every day.
 

References

  1. Kazandjian. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016;43(6):676-681. doi:10.1053/j/seminoncol.2016.11.004
  2. Cowan AJ, Allen C, Barac A, et al. Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study 2016. JAMA Oncol. 2018;4(9):1221–1227. doi:10.1001/jamaoncol.2018.2128
  3. Abramson HN. Clin Lymphoma Myeloma Leuk 2018;18:611–27.
  4. Kumar SK, et al. Leukemia 2012;26:149–57.
  5. Myeloma 5-year SEER survival. Available at: https://seer.cancer.gov/explorer/index.html [Accessed 18 July 2019];
  6. Yang W, Lin S. Mechanisms of Drug Resistance in Relapse and Refractory Multiple Myeloma. BioMed Research International 2015. doi: 10.1155/2015/341430.
  7. Cancer stat facts: Myeloma. Available at: https://seer.cancer.gov/statfacts/html/mulmy.html [Accessed 18 July 2019].
  8. Sonneveld P, et al. Blood 2016;127:2955–62;
  9. Faiman B et al. Clin J Oncol Nurs 2017;21(5 Suppl):19–36
  10. Maes H, Delforge M. Exp Rev Hematol 2015;8:355–66.
  11. Usmani S, et al. Oncologist 2016;21:1355–61
  12. Larsen J, Kumar S. Evolving Paradigms in the Management of Multiple Myeloma: Novel Agents and Targeted Therapies. Rare Cancers Ther. 2015; 3: 47–68. doi:10.1007/s40487-015-0009-4.
  13. Nooka A, Kastritis E, Dimopoulos M, et al. Treatment options for relapsed and refractory multiple myeloma. Blood 2015 125:3085-3099; doi: https://doi.org/10.1182/blood-2014-11-568923.
  14. Jiang H, et al. Leukemia 2016;30:399–408.
  15. Hulin C, Hansen T, Heron L et al. Living with the burden of relapse in multiple myeloma from the patient and physician perspective. Leuk Res. 2017 Aug;59:75-84. doi: 10.1016/j.leukres.2017.05.019. Epub 2017 May 31.


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