Advances in Multiple Myeloma, Lymphoma, and Histiocytosis among Results Presented at 2017 ASH Meeting

By Jim Stallard,

Tuesday, December 12, 2017

A crowd at the meeting of the American Society for Hematology

With more than 20,000 attendees, the American Society of Hematology (ASH) annual meeting is the world’s largest event devoted to the study of blood cancers. At the 2017 meeting, held December 9 to 12 in Atlanta, Memorial Sloan Kettering researchers reported important progress in the treatment of several blood cancers.

Multiple Myeloma: Developing the Best CAR T Cell Therapy

Chimeric antigen receptor (CAR) T cell therapy, which uses genetically engineered versions of a person’s own immune cells to fight cancer, has already shown great promise in treating some types of leukemia and lymphoma. Medical oncologist Eric Smith presented encouraging results from efforts to design and test CAR T cell therapy to treat advanced multiple myeloma.

Current treatments can control multiple myeloma, but the disease is incurable. When it does relapse, it becomes resistant to further treatment.

To address this, researchers are engineering CAR T cells to recognize and attack a protein called BCMA. The CAR therapies that have been FDA approved thus far target a molecule called CD19. It is found on other blood cancers but not multiple myeloma. BCMA, however, is found on the surface of myeloma cells, representing a new target for CAR T cell therapy.

Side-by-side body scans of woman. Left scan shows tumors throughout body. Right scan shows tumors nearly gone.

To find a treatment that targets BCMA with great precision, the MSK team screened many receptors to see which made the most effective CAR T cells. They tested the top candidates against human myeloma cells and in mouse models for the disease.

“This CAR is very specific for BCMA and not other human proteins. It really only targets myeloma cells and not other primary human cell types,” Dr. Smith says.

Preliminary results from a phase I clinical trial at MSK have shown the BCMA-targeted CAR T therapy to be safe at low levels. MSK researchers are slowly raising the dosage to find the ideal amount and there has already been one striking outcome. PET scans had initially showed myeloma all over a female patient’s body, but four weeks after receiving CAR T cells, the tumors had shrunk dramatically or vanished. She remains in a complete remission more than three months after treatment. (The woman had to discontinue from the clinical trial for unrelated reasons.)

“That’s an exciting result that shows this therapy can be effective,” Dr. Smith says.

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Hodgkin Lymphoma: A New Frontline Treatment Approach

A better treatment may soon be available for people with Hodgkin lymphoma, according to results from ECHELON-1, a randomized, multicenter, phase III clinical trial. The study compared the standard chemotherapy regimen ABVD against the drug brentuximab vedotin (Adcetris®) with the chemotherapy regimen AVD.

The trial tested how well brentixumab vedotin plus AVD would work as an initial treatment in people with advanced Hodgkin lymphoma, many of whom were enrolled at MSK. In the trial, 1,334 people were randomly split into two groups. One got brentuximab vedotin plus AVD. The other got the standard ABVD therapy.

After decades of stalemate, we will have an important new treatment option to offer people with advanced-stage Hodgkin lymphoma.
Anas Younes
Anas Younes Chief, Lymphoma Service

Results showed that brentuximab vedotin plus AVD increased the proportion of people with advanced Hodgkin lymphoma who were disease free after two years by approximately 5% (from 77% to 82%) compared with the standard treatment.

Anas Younes, Chief of the Lymphoma Service at MSK, and medical oncologist David Strauss are co-authors on the study, which was published in the New England Journal of Medicine.

“This is an important milestone for Hodgkin lymphoma treatment, which was based on promising results from a phase I trial that we led a few years ago,” Dr. Younes says. “After decades of stalemate, we will have an important new treatment option to offer people with advanced-stage Hodgkin lymphoma.”

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Follicular Lymphoma: PET Imaging Guides Therapy

Another study, led by Dr. Younes and presented by MSK medical fellow Anna Alperovich, sheds important light on follicular lymphoma, one of the most common forms of non-Hodgkin lymphoma. The disease is typically slow-growing and does not always need treatment right away. It sometimes turns into a more aggressive disease called diffuse large B cell lymphoma, which calls for intensive treatments.

Computed tomography (CT) is used routinely on people after they receive their first treatment. CT can determine if the therapy is working and predict survival. In recent years, research has shown that people whose follicular lymphoma progresses within two years of initial therapy have poor survival rates. A consensus was starting to build among lymphoma experts that these people might need aggressive treatment, such as a bone marrow transplant or CAR T cell therapy. The two-year mark was becoming an important factor in treatment decisions.

But Dr. Younes’s team found that the limitations of CT scans may have muddied the issue. When PET scans were used to stage follicular lymphoma, people whose disease progressed within two years did not fare much worse than others. This suggests that the significance of two-year progression should be re-examined.

Dr. Younes thinks the discrepancy arose because CT scans were failing to detect follicular lymphoma cases that had become diffuse large B cell lymphoma, and both types — aggressive and slower growing — were being lumped together. PET imaging, used widely today, does a better job than CT scans of detecting the transformed cases.

“For the last five or six years, everyone has wondered whether we need to change the standard treatment for people with follicular lymphoma who progressed within two years,” he says. “Our data suggest that in today’s PET-staging era, progression of disease within two years from the start of treatment may not be as bad as we initially thought. More work needs to be done to confirm these results before we change the standard of care for these people.”

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Histiocytosis: Expanding the Spectrum of Treatable Cases

MSK neuro-oncologist Eli Diamond reported on promising news for people with rare blood diseases known as histiocytic disorders. This group includes Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis. Histiocytic disorders have long lacked effective treatments. But recently a targeted therapy became available, and another may soon be on the way.

In November 2017, the FDA approved vemurafenib (Zelboraf®) for the treatment of ECD. Vemurafenib blocks a genetic mutation called BRAF V600, which is present in about half of people with histiocytic disorders.

But many people with histiocytosis don’t carry the mutation, or if they do, they are unable to take vemurafenib because of side effects. For this group, another target was needed to block the cancer growth. Genetic analysis of their tumors using a test called MSK-IMPACT™ revealed that nearly all of them have mutations in a cancer pathway called MAPK. One of the main proteins in this pathway is called MEK. Drugs targeting MEK have already proven effective in people with melanoma.

Dr. Diamond presented results from a phase II trial testing a MEK inhibitor called cobimetinib (Cotellic®) in people with histiocytic diseases. Most did not have the BRAF mutation, although some did. In the study, 14 of 16 people with histiocytosis had improvement in their PET scans, indicating shrinkage of their tumors. This suggests that cobimetinib could be effective regardless of BRAF status. It could provide another effective treatment option for these rare diseases.

“These results broaden the spectrum of people with histiocytosis who can be effectively treated with a single targeted drug,” Dr. Diamond says.

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