otlogo
​​​​
​​​​​​

Enhancing the Immune System Against Multiple Myeloma to Plug Gaps in Care 

by Jeff Settleman, Ph.D. 

Our children, parents, friends, colleagues – when it comes to the people we love, blood cancers do not discriminate and can strike at any age, with more than a million people worldwide diagnosed in 2020.1,2​ That's why our goal to find effective treatments for all blood cancers is so urgent. 

Although there are many treatments available for multiple myeloma – a blood cancer that affects plasma cells made in the bone marrow – none are currently curative. Relapse is nearly inevitable. Despite treatment advances in the last decade, the median life expectancy for people living with the disease remains just over five years.3​

As multiple myeloma is a cancer of the bone marrow, rapidly expanding tumors crowd out the normal cells that share the same space, causing anemia and immune dysfunction. The cancerous cells also secrete harmful proteins that damage the kidneys and weaken the surrounding bone, leading to fractures and pain.

In addition to the physical symptoms people living with multiple myeloma often endure, the relapsing nature of the disease can feel like an emotional rollercoaster. As their cancer develops resistance to formerly effective therapies, they bounce from one treatment to the next. Each time the cancer comes back, the remission period gets shorter, and the prognosis gets worse. As patients progress, they exhaust the available treatments, creating a need for new options. 

The American Cancer Society estimates approximately 34,000 new cases of multiple myeloma will be diagnosed this year and 13,000 people will die of the disease in the U.S.4​ Multiple myeloma is primarily a disease of the elderly, with a median age at diagnosis of 66–70 years, and it disproportionately impacts ethnic and racial minority groups in both incidence, outcome, and onset, with Black patients tending to have an earlier average age at diagnosis — by 5 to 10 years.5,6​ Yet, elderly patients and ethnic minority groups continue to be underrepresented in cancer clinical trials and studies. 

At Pfizer, we are focused on removing barriers for people living with cancer – especially for underserved communities who historically have not always received optimal care, including people over the age of 65, racial and ethnic minorities, and people living in rural areas. The Pfizer Clinical Development Program aims to enroll participants who represent the real-world patient populations impacted by multiple myeloma, using a variety of collaborations and proactive outreach programs to support recruitment. Our clinical trials are also planned and executed with Pfizer's Diversity in Clinical Trials Center of Excellence, which provides detailed demographic data on the epidemiology of the disease, allowing the teams to make informed decisions when selecting investigators and sites.

Despite the challenges of managing multiple myeloma, the field is constantly innovating, providing patients with novel options. In this era of immunotherapy and precision medicine, the tools at our disposal are better than ever. Pfizer has taken bold new approaches over the past decade to translate scientific research into effective medicines for people living with hematologic malignancies.

​As cancer researchers, our goal is to help our patients live their lives to the fullest. Pfizer is investing in game-changing science to deliver tomorrow's breakthroughs, so our patients are present for those milestone moments, like attending their child's wedding, while also being pain-free and having the energy to dance. Advancements in blood cancer care start with the spirit of never settling. 


A New Target Emerges 

Like most cancers, multiple myeloma was traditionally treated with the blunt tools of chemotherapy and radiation. Later, the advent of proteasome inhibitors, immunomodulatory agents and monoclonal antibodies presented patients with more options, resulting in prolonged life, but relapse is still common. Stem cell transplant can provide long-lasting remission, but is a risky procedure.6​

The field entered a new era with the discovery of a protein on the surface of myeloma cells called B-cell maturation antigen (BCMA).7​ BCMA is highly specific to myeloma cells and expressed in abundance, so it presents cancer researchers with a key to unlock precision medicine, targeting the cancer preferentially.8

There have been several different approaches to exploiting BCMA in the treatment of multiple myeloma. One involves the creation of antibody-drug conjugates, which bind to BCMA on the surface of myeloma cells and deliver a chemotherapy to kill the tumor cells. Another involves chimeric antigen receptor T-cell therapy (CAR-T), where a patient's own T-cells are collected, genetically modified so they can identify BCMA on the surface of myeloma cells, and then put back into the body, where they attack the cancer cells. 


Pulling Immune Cells and Cancer Cells Together 

Nearly a decade ago, Pfizer began investigating a different way to use BCMA to treat multiple myeloma, using bispecific antibodies (BsAbs). BsAbs are a novel type of cancer immunotherapy that bind to and engage two different targets at once. One arm binds directly to specific antigens on cancer cells, and the other arm binds to the T-cell, bringing both cells together. This binding activates the person's own immune system to kill the targeted cancer cells. Data from clinical trials suggest BsAbs have a manageable safety profile, with encouraging efficacy in treating relapsed or refractory multiple myeloma.8​,9 Trials with these agents are ongoing in various settings of multiple myeloma.

We realize the need is immediate for people living with this blood cancer, especially those who have relapsed on previous treatment. Pfizer's in-depth understanding of the science behind blood cancers and our heritage across existing blood cancer medicines positions us for success. We are motivated by the belief that science can win. 


To learn more, please visit www.mmwayforward.com and follow @Pfizer on Twitter
 
Jeff Settleman is the Chief Scientific Officer for Oncology Research and Development at Pfizer. 
 


References: 

1. Worldwide cancer data. World Cancer Research Fund International. https://www.wcrf.org/cancertrends/worldwide-cancer-data/. Accessed April 29, 2022.

2. Sung H, Ferlay J, Siegel Rl, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249.

3. Multiple Myeloma Research Foundation. Understanding survival statistics. https://themmrf.org/multiple-myeloma/prognosis/understanding-survival-statistics/. Accessed May 17, 2022.

4. American Cancer Society. Key statistics about multiple myeloma. https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html. Accessed May 17, 2022.​

6. American Cancer Society. Stem cell or bone marrow transplant side effects. https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/stem-cell-transplant/transplant-side-effects.html. Accessed October 13, 2022

7. Kleber M, Ntanasis-Stathopoulos I, Terpos E. BCMA in multiple myeloma-A promising key to therapy. J Clin Med. 2021;10(18):4088. Published 2021 Sep 10.

8. Carpenter RO, Evbuomwan MO, Pittaluga S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res 15 April 2013; 19 (8): 2048–2060.

9.  Sebag M, Raje NS, Bahlis NJ, et al. Elranatamab (PF-06863135), a B-cell maturation antigen (BCMA) targeted CD3-engaging bispecific molecule, for patients with relapsed or refractory multiple myeloma: Results from MagnetisMM-1. Blood 2021; 138 (Supplement 1): 895. ​​