Close

Double your impact Match My Donation

Immunotherapy for Multiple Myeloma

Let's spread the word about Immunotherapy! Click to share this page with your community.
Copy Link
  • Multiple Myeloma
  • Treatment Options
  • CRI's Impact
  • Clinical Trials

How is Immunotherapy Changing the Outlook for Patients with Multiple Myeloma?

Reviewed By: Hearn Jay Cho, M.D., Ph.D.
Details
Assistant Professor of Medicine, Mount Sinai School of Medicine, and Attending Physician, Multiple Myeloma Service, Mount Sinai Tisch Cancer Institute
Share

Multiple myeloma is one of the major cancer types for which new immune-based cancer treatments are currently in development. This page features information on multiple myeloma and immunotherapy clinical trials for multiple myeloma patients, and highlights the Cancer Research Institute’s role in working to bring effective immune-based cancer treatments to people with multiple myeloma.

Myeloma—also referred to as multiple myeloma or plasma cell myeloma—is a cancer that originates in plasma cells, a type of white blood cell that makes antibodies. The myeloma cells grow in an out-of-control manner and accumulate in the bone marrow throughout the body. Over time, the tumor cells may directly damage the bones, causing fractures and dangerously elevated blood calcium levels, and may damage the kidneys. Myeloma cells interfere with blood production, resulting in anemia or low red blood cell counts. They also suppress normal antibody production, interfering with normal immunity and leaving the patients vulnerable to infections.

Urgent Need

Multiple myeloma is the second-most common form of blood cancer in the U.S, comprising about 1% of all cancers. There are approximately 30,330 new cases of myeloma in the U.S. every year, and 12,650 deaths caused by the disease. In the U.S., it is estimated that 1 in 150 men and women will develop myeloma at some point in their lifetimes.

Treatment

The diagnosis of multiple myeloma is made by the presence of elevated abnormal plasma cells in the bone marrow. However, treatment decisions are based on symptoms of organ damage from the disease, such as bone damage, high blood calcium, anemia, kidney failure, and/or recurrent infections. In some cases, individuals present with “smoldering” or asymptomatic myeloma. These patients are subject to “watchful waiting,” observation without therapy while monitoring for the development of symptoms. Standard treatments for symptomatic myeloma include chemotherapy with drugs like bortezomib (Velcade®), lenalidomide (Revlimid®), ixazomib (Ninlaro®), and panobinostat (Farydak®), autologous stem cell transplantation, and, in some cases, radiation therapy.

In 2015, daratumumab (Darzalex™) and elotuzumab (Empliciti™) were approved by the FDA. Daratumumab is an antibody that binds to CD38, a protein found in most multiple myeloma cells. It was approved for patients who have received at least three prior lines of therapy. Elotuzumab targets the SLAMF7 receptor, which is present on both myeloma cells and natural killer (NK) cells. This enhances the immune response through multiple mechanisms: by attaching to the myeloma cells, it marks them for destruction, and by attaching to the NK cells, it primes the immune cells to search for and attack the myeloma cells. It was approved, in combination with two other therapies, for patients who have received one to three prior medications.

CRI Contributions and Impact

Through its multiple myeloma initiative and other grant programs, CRI is supporting several basic and clinical studies that are advancing the understanding and immunologic treatment of multiple myeloma. Investigations currently focusing on multiple myeloma include:

  • CRI postdoctoral fellow Diego Acosta-Alvear, Ph.D., at the University of California, San Francisco, is studying how a mechanism called the unfolded protein response contributes to multiple myeloma progression. Through his studies, Dr. Acosta-Alvear has successfully developed a mouse model for multiple myeloma, overcoming a key challenge in myeloma research to date. The model recapitulates manifestations of the disease, allowing for whole body, non-invasive, real-time measurements of tumor progression.
  • At Memorial Sloan Kettering Cancer Center, CRI predoctoral fellow Eleanor Tyler is studying the involvement of T cell responses specific to the myeloma antigens CT7/MAGE-C1 and WT1 in disease regression following stem cell transplantation. Their results demonstrate the consistent co-expression of CT7 and WT1 with CD138 in malignant plasma cells. Importantly, their findings suggest a correlation between the emergence of CT7- and WT1-specific T cells post-transplantation, and disease regression in patients being treated for relapsed multiple myeloma. These data support the development of adoptive immunotherapeutic approaches utilizing myeloma-specific T cells for patients with multiple myeloma.
  • Djordje Atanackovic, M.D. (CRI Investigator, 2007-2011), and colleagues at the University Medical Center Hamburg-Eppendorf, in Hamburg, Germany, identified the cell receptor CD229 as the most strongly over-expressed antigen in multiple myeloma, suggesting that it could be a promising target for anti-myeloma therapies. Further studies demonstrated that limiting the expression of this receptor could decrease the number of myeloma cells and enhance the anti-tumor activity of conventional chemotherapies, and that blocking CD229 with a monoclonal antibody resulted in the destruction of myeloma cells. These results are a significant first step toward the development of a novel and promising targeted anti-myeloma therapy.
  • The recipient of a CRI Coordinated Cancer Initiative grant, Hearn Jay Cho, M.D., Ph.D. (Multiple Myeloma Working Group Grant), at Mount Sinai School of Medicine, is conducting clinical trials of promising immunotherapies for myeloma targeting the MAGE-A3 antigen. In work funded by the CRI, Dr. Cho discovered that two of the type I Melanoma Antigen Genes (MAGE), MAGE-A3 and CT7/MAGE-C1, are expressed in the tumors of more than 75 percent of myeloma patients. He and his colleagues also demonstrated that MAGE-A3 is a critical survival factor in multiple myeloma that makes these cells resistant to normal cell death and killing by chemotherapy agents, providing further evidence that MAGE proteins may be excellent candidates for tumor vaccines targeting multiple myeloma. In particular, he discovered a functional role for MAGE-A3. In a paper published online in May 2011 in the journal Clinical Cancer Research, Dr. Cho demonstrated that MAGE-A3 contributes to cancer progression by rendering myeloma cells more resistant to apoptosis, the cell death program that is one of the body’s major defenses against cancer. These studies provide strong evidence for MAGE-A3 as a target for anti-myeloma therapy, and that strategies targeting MAGE-A3 may result in myeloma cell death and prevent disease recurrence. Combination immunotherapy targeting myeloma-associated MAGE antigens is anticipated to become an important weapon to combat this incurable disease.

“Being able to monitor patient immune responses to myeloma antigens over the course of their disease, and to correlate these responses to disease load, means that our work really moves from the bedside to the bench and back. Few cancers have such a readily available disease marker to follow. It is exciting to see this work evolve into new therapeutic approaches.”

- Eleanor Tyler, CRI Predoctoral Fellow

Featured Patient

Once you choose hope, anything is possible.

Kristin Kleinhofer
Leukemia  |  Diagnosed 2010
Read My Story
Featured Scientist
Markus Muschen, M.D., Ph.D.
City of Hope National Medical Center
CLIP Investigator  |  2016
View Funding Profile

Multiple Myeloma Statistics

2nd Most common form of blood cancers
1 in 150 Men and women will develop myeloma in their lifetime
6 Types of immunotherapy clinical trials

AmazonSmile Holiday Shopping Ad

Amazon donates 0.5% of the price of your eligible AmazonSmile purchases to the charitable organization of your choice. AmazonSmile is the same Amazon you know. Same products, same prices, same service. Support Cancer Research Institute by shopping at smile.amazon.com.

Clinical Trials for Multiple Myeloma

Immunotherapies are a promising new strategy to fight multiple myeloma. The only documented long-term complete remissions reported in multiple myeloma patients have occurred with allogeneic bone marrow transplantation, where a donor’s blood stem cells (graft) are transplanted into the patient (host) with multiple myeloma. The new immune system that grows from the donor stem cells can recognize myeloma cells as “foreign” and kill them, which is known as the “graft-vs-myeloma” effect. This demonstrates that the immune system can eradicate multiple myeloma cells.

Most multiple myeloma patients, however, are ineligible for allogeneic transplantation due to age and medical restrictions. Innovative approaches to harness the immune system to fight multiple myeloma and stimulate a “host-vs-myeloma” effect will benefit the majority of myeloma patients.

Therapies
  • Checkpoint Inhibitors
  • Cancer Vaccines
  • Cytokines
  • Adoptive Cell Therapy
  • Antibodies
  • Oncolytic Virus Therapies

A promising avenue of clinical research in multiple myeloma is the use of immune checkpoint inhibitors. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.

Nivolumab (Opdivo®): A PD-1 Antibody +/- Ipilimumab (Yervoy®): A CTLA-4 Antibody
  • A phase III trial of nivolumab, elotuzumab, pomalidomide, and dexamethasone in patients with multiple myeloma (NCT02726581).
  • A phase I/II study of nivolumab plus ipilimumab after a stem cell transplant in patient with multiple myeloma at high-risk for recurrence (NCT02681302).
  • A phase I trial testing nivolumab and ipilimumab in patients with blood cancers, including multiple myeloma (NCT01592370).
  • A phase I clinical trial of the nivolumab in patients with hematological malignancies, including myeloma (NCT01592370).
Durvalumab (MEDI4736): A PD-L1 Antibody +/- Tremelimumab: A CTLA-4 Antibody
  • A phase I/II trial to test durvalumab (MEDI4736) and daratumumab in patients with relapsed or refractory multiple myeloma (NCT02807454).
  • A phase I trial to test tremelimumab and durvalumab, with high-dose chemotherapy and a stem cell transplant, in patients with relapsed or refractory multiple myeloma (NCT02716805). The Cancer Research Institute is sponsoring this trial.
  • A phase I trial to test durvalumab as monotherapy or in combination with pomalidomide in patients with relapsed or refractory multiple myeloma (NCT02616640).
  • A phase I trial of durvalumab plus lenalidomide +/- dexamethasone in patients with newly diagnosed multiple myeloma (NCT02685826).
Pembrolizumab (Keytruda®, MK-3475): A PD-1 Antibody
  • A phase III trial to test pomalidomide +/- pembrolizumab in patients with relapsed or refractory multiple myeloma (NCT02807454).
  • A phase III trial to test lenalidomide and dexamethasone +/- pembrolizumab in patients with newly diagnosed treatment-naïve multiple myeloma (NCT02579863).
  • A phase II trial for patients with multiple myeloma with residual disease (NCT02636010).
  • A phase I trial for patients with multiple myeloma (NCT02036502).
  • A pilot trial in patients with smoldering multiple myeloma (NCT02603887).
  • A phase I trial for patients with blood cancers, including multiple myeloma (NCT01953692).
Atezolizumab (Tecentriq™, MPDL3280A): A PD-L1 Antibody
  • A phase I study in patients with asymptomatic myeloma (NCT02784483).

Cancer vaccines are designed to stimulate an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens.

  • A phase II trial of dendritic cell vaccine in patients with in multiple myeloma (NCT02728102).
  • A phase II trial of a cancer vaccine, PVX-410, after a stem cell transplant in patients with multiple myeloma (NCT02700841).

 

Cytokines are messenger molecules that help control the growth and activity of immune system cells. Several antibodies that block or stimulate cytokine pathways important to myeloma are under development.

  • ALT-803, an interleukin 15 (IL-15) agonist, is being studied in relapsed or refractory multiple myeloma in two phase I/II trials (NCT02099539NCT01885897).
  • A phase I/II trial of SL-401, an interleukin 3 receptor (IL-3R), present on a wide range of hematologic cancers, in patients with relapsed or refractory multiple myeloma (NCT02661022).

 

Another major avenue of immunotherapy for multiple myeloma is adoptive cell transfer. In this approach, T cells are removed from a patient, genetically modified or treated with chemicals to enhance their activity, and then re-introduced into the patient with the goal of improving the immune system’s anti-cancer response. Several trials of adoptive T cell transfer techniques are currently under way for patients with multiple myeloma, including:

  • A phase II study to test chimeric antigen receptor (CAR) T cell therapy targeting CD19 for patients with multiple myeloma (NCT02794246).
  • A phase I trial of CAR T cell therapy targeting tumor necrosis factor (TNF) receptor superfamily member 17 (TNFRSF17), also called CD269, in patients with multiple myeloma (NCT02658929).

 

Monoclonal antibodies are molecules, generated in the lab, that target specific antigens on tumors. Many antibodies are currently used in cancer treatment, and some appear to generate an immune response.

  • A phase I trial testing AMG 224, an antibody-drug conjugate, in patients with relapsed or refractory multiple myeloma (NCT02561962).
  • Two phase I trials testing isatuximab (SAR650984), a CD38 antibody, in patients with newly diagnosed multiple myeloma (NCT02513186) and relapsed or refractory multiple myeloma (NCT02514668).

 

Oncolytic virus therapy uses a modified virus that can cause tumor cells to self-destruct and generate a greater immune response against the cancer.

  • A phase I trial of reovirus, plus bortezomib and dexamethasone, for patients with relapsed or refractory multiple myeloma (NCT02514382).

For a complete list of open clinical trials for multiple myeloma, see our Clinical Trial Finder.

 

Find an immunotherapy clinical trial
  • Search Online
  • Phone
  • Email

Create a profile and fill out a questionnaire to identify immunotherapy clinical trials for which you may be eligible.

CALLING HOURS  |  M-F 8:30 a.m. to 6 p.m. ET
Se habla espanol

Request a call from a Clinical Trial Navigator

LEARN MORE ABOUT CLINICAL TRIALS

American Cancer Society; SEER Cancer Statistics Factsheets: Myeloma; Weir HK et al. Annual report to the nation on the status of cancer, 1975-2000, featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst. 2003; Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004; Altor Bioscience Corp.; ClinicalTrials.gov; CRI documents

Updated September 2016

*Immunotherapy results may vary from patient to patient.

Top