Debu Tripathy, M.D.

Dr. Debu Tripathy, Professor of Medicine Chair, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center.

An innovative and groundbreaking cancer treatment has been made available earlier to patients with multiple myeloma, as chimeric antigen receptor (CAR)-T cell therapy is propelled ever closer to the front line of treatment.

In this special issue of CURE, we spotlight the use of CAR-T cell therapy in recent years to treat multiple myeloma, a cancer of the plasma cells — a type of immune cell that produces antibodies. CAR-T cell therapy involves extracting, modifying and reinfusing a patient’s own T cells, a type of immune cell, to specifically recognize and attack cancer cells.

“Cancers of the immune system often know all the tricks of the immune system and are able to bypass them,” Dr. Rahul Banerjee, assistant professor in the division of hematology and oncology at the University of Washington and assistant professor in the clinical research division at the Fred Hutch Cancer Center, both in Seattle, told CURE. “With CAR-T, you level the playing field.”

The first Food and Drug Administration (FDA) approval of a CAR-T cell therapy to treat multiple myeloma, Abecma (idecabtagene vicleucel),came in 2021, followed by Carvykti (ciltacabtagene autoleucel) in 2022. Both were approved for patients who had received at least four prior lines of treatment, but earlier this year, the FDA approved Abecma for patients who had received two prior lines of therapy and Carvykti for patients who had received one prior line of treatment. Successful treatments are often eventually tested at earlier stages of therapy, although

safety and toxicities are important factors in sorting out the optimal sequence of deployment.

We spoke with experts about current clinical trials evaluating CAR-T cell therapy in even earlier lines of therapy as well as developments in treatment strategies. We also discuss the challenges,

side effects and potential of these treatments as they currently exist.

“I would say [for] CAR-T cells in general, not just for myeloma but for all cancers, we’re in the same place as we were for stem cell transplantation back in the ’70s and early ’80s,” Dr. Saad Usmani, chief of myeloma service at Memorial Sloan Kettering Cancer Center in New York City, said.

“We have a long way to go. And I think we’ll be able to develop very effective therapies using this technology in the future.”

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Articles

Three years after the first FDA approval of CAR-T cell therapy, patients with multiple myeloma are starting to see the therapy emerge in earlier lines. 

Moving Forward in Multiple Myeloma: Earlier Lines of CAR-T Cell Therapy

Dr. Debu Tripathy of The University of Texas MD Anderson Cancer Center and CURE Editor-in-Chief discussed the changing landscape as cancer vaccines enter the picture.

In the pursuit of groundbreaking cancer therapies, the spotlight has shifted to a promising frontier: cancer vaccines. In this issue, we explore the revolutionary potential of personalized mRNA-based vaccines as well as off-the-shelf options, offering a glimpse into the evolving landscape of immuno-oncology.

The combination of mRNA technology and immunotherapy, exemplified by mRNA-4157 paired with Keytruda (pembrolizumab), has emerged as a new potential treatment option for melanoma, with results from the landmark KEYNOTE-942 trial underscoring the efficacy of this combination. This is essentially a one-two punch of distinct pathways of the immune system — one mutation-specific and another that generates a broader immunological reaction.

“The main reason why this is exciting is the fact that this is the clearest sign that these vaccines can be likely active, and they can actually prevent a melanoma recurrence from happening,” said Dr. Patrick Ott, of the Dana-Farber Cancer Institute in Boston.

While researchers are pioneering personalized vaccines, such as mRNA-4157, that target unique mutations present in tumor cells, there have also been strides made in the development of off-the-shelf vaccines, such as ELI-002 2P, which is intended to enable a patient’s immune system to identify and destroy pancreatic and colorectal cancer cells with cancer-driving KRAS G12D and G12R mutations commonly seen in these cancer types.

The timeline for cancer vaccines’ general availability is unknown, with Dr. Jay Berzofsky of the National Cancer Institute telling 

such treatments won’t be available this year, or probably even next year.

“But, on the other hand, I think if something is really successful, the [Food and Drug Administration] has ways of fast-tracking approval,” Berzofsky said. “So, if there’s a real home run, then it might happen faster than we think, and that would be wonderful.”

We have come a long way in cancer immunology with newer discoveries of the intricacies of how our bodies recognize cancer cells and mount an immune response, along with innovative ways to boost that further. This is a result of sustained research with newer tools that will accelerate this trend. I suspect a growing fraction of the next generation of cancer drugs will be immunological.

With many groundbreaking cancer therapies on the horizon, it's also time to focus on up and coming cancer vaccines. 

Shifting the Spotlight to Cancer Vaccines

"In the landscape of cancer treatment, stories of dedication and breakthroughs often intertwine, offering hope amid the challenges faced by patients." 

Professor of Medicine Chair, Department of Breast Medical Oncology
The University of Texas MD Anderson Cancer Center

In the landscape of cancer treatment, stories of dedication and breakthroughs often intertwine, offering hope amid the challenges faced by patients. In this 

, we examine the impressive potential of antibody-drug conjugates (ADCs) in the treatment of bladder cancer, a class of drugs showing greater activity that we have seen with prior chemotherapy agents.

Antibody-drug conjugates, described by Dr. Yousef Zakharia of the University of Iowa as “targeted chemotherapy,” are designed to deliver a payload of chemotherapy directly to cancer cells, thereby intended to spare healthy cells from the impact of toxic treatments.

with the discovery of bladder cancer three years ago, leading to a series of treatments including surgery, chemotherapy and immunotherapy. Despite these efforts, she experienced multiple recurrences, but has had no evidence of disease for more than a year since starting treatment with Padcev (enfortumab vedotin-ejfv), an ADC that is reshaping the landscape of bladder cancer treatment.

Padcev’s transformative impact was high- lighted by the remarkable results of the EV-302 clinical trial, which revealed significantly improved outcomes compared to traditional chemotherapy, a near doubling of the median time to tumor progression.

Padcev and Keytruda (pembrolizumab) combination therapy 

by the Food and Drug Administration in December 2023 for patients with locally advanced or metastatic bladder cancer represents a pivotal event, one described as a “eureka moment” by Dr. Bamidele Adesunloye, medical oncologist at City of Hope Atlanta.

Yet, as Zakharia aptly notes, the quest for a cure remains ongoing. While ADCs represent a significant stride forward, they are not without their challenges. Unmet needs persist, reminding us of the imperative to continue the pursuit of innovation and progress in cancer care.

“Certainly, we are heading [in] that direction,” he said, “but we are far away from curing everybody.” Further innovations in the more precise delivery of increasingly more potent drugs directly to tumor cells while protecting normal cells and tissue are expected over time.

Reshaping the Landscape of Bladder Cancer Treatment

In this issue of CURE, we examine the science behind bispecific antibodies such as Tecvayli (teclistamab-cqyv) — how they work and the impact they have had on patients with multiple myeloma.

Those patients include Cindy Brown, who in 2020 joined a clinical trial at the City of Hope Comprehensive Cancer Center in Los Angeles for Tecvayli, an immunotherapy drug that targets a protein called B-cell maturation antigen, or BCMA, found specifically on multiple myeloma cells. Tecvayli activates a patient’s immune system by binding to the CD3 receptor on T cells and the BCMA protein on myeloma cells. Bispecific antibodies act as a bridge and can bring cells or proteins on the cell membrane together to facilitate certain processes like triggering the immune system.

Therapies such as Tecvayli offer providers a targeted approach, honing in on cancer cells while sparing healthy tissues with the goals of fewer side effects and better outcomes for patients. With the FDA approval of Tecvayli and other BCMA-targeted therapies like Elrexfio (elranatamab-bcmm), a new era in multiple myeloma treatment has arrived.

However, questions persist regarding the optimal timing and sequencing of these therapies, as well as potential mechanisms of resistance and long-term management strategies. Ongoing research continues to examine these complexities, pointing the way toward potential future breakthroughs and treatment options.

More CURE® coverage on multiple myeloma:

Early Intro to Carvykti Is 'Promising' for Patients With Myeloma

Linvoseltamab to Be Reviewed for Relapsed, Refractory Myeloma

FDA Approves Dosing Reduction of Tecvayli in Relapsed, Refractory Myeloma

Blenrep Combo for Relapsed, Refractory Myeloma Improves Outcomes

Newer technologies can speed up innovations needed to refine this approach, and the next generation of drugs are likely to be even more powerful and applicable to a growing list of cancer types.

Cindy’s story is illustrative of the impact that immunotherapy has had in transforming the lives of patients with cancer.

“It’s been remarkable for me in terms of success. It’s super well-tolerated,” Brown says. “If you met me and didn’t know who I was, you would have no idea I was sick.”

Professor of Medicine Chair, Department of Breast Medical Oncology

The University of Texas MD Anderson Cancer Center

Here is a run-down of some topics we covered in the Spring 2024 issue of CURE.

Debu Tripathy, M.D.

Moving Forward in Multiple Myeloma: Earlier Lines of CAR-T Cell Therapy

Shifting the Spotlight to Cancer Vaccines

Reshaping the Landscape of Bladder Cancer Treatment

The Impact of Immunotherapy on Multiple Myeloma

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