This Clinician’s View is written by AdventHealth Cancer Institute Medical Director of Stem Cell Transplant and Cellular Therapy Rushang Patel, MD, PhD.
Historically, multiple myeloma has been considered a chronic, incurable blood cancer marked by inevitable relapse. Now, some clinicians are asking whether a functional cure for some patients may be within reach.
Over the past decade, we have made remarkable advances in targeted immunotherapy and are now producing outcomes that were once considered unattainable. For the first time, emerging therapies are achieving deep, sustained minimal residual disease (MRD)-negative remissions in multiple myeloma, and in some cases, without the need for continuous treatment. These results are redefining our expectations.
At AdventHealth Cancer Institute (AHCI), we are utilizing comprehensive genomic and molecular profiling at the time of diagnosis to better understand each patient's disease biology and tailor treatment accordingly. We are also providing our patients access not only to newly approved therapies, but also to next-generation investigational treatments through clinical trials.
This combined approach is moving us toward truly personalized therapy as we continue to shape the future of myeloma treatment. Most importantly, these innovations are translating into longer remissions, improved quality of life, and new hope for patients and families.
The rise of immunotherapy has been one of the most significant drivers of this progress.
The Role of Immunotherapy in Treating Multiple Myeloma
Multiple myeloma is a complex hematologic malignancy driven by the expansion of abnormal plasma cells within the bone marrow. Patients have historically been treated with combinations of proteasome inhibitors, immunomodulatory drugs (IMiDs) and monoclonal antibodies, often supplemented by stem cell transplantation in appropriate candidates. However, the disease is marked by cycles of remission and relapse, with treatment resistance often emerging over time, limiting the long-term effectiveness of the conventional treatment strategies.
Unlike traditional chemotherapy, which directly attacks both malignant cells and healthy cells, immunotherapy harnesses and enhances the body's own immune system to recognize, target and destroy mainly the harmful cells. Some of the most exciting immunotherapies that have emerged for treating multiple myeloma include CAR-T cell therapy, bispecific antibodies and emerging trispecific antibodies.
These new treatment options are changing what is possible for patients with multiple myeloma. However, maximizing their effectiveness begins with better understanding each individual patient’s disease biology and using that information to personalize treatment decisions.
Delivering Precision Medicine to Personalize Cancer Care
In addition to advancing the development and delivery of novel immunotherapies for multiple myeloma, AdventHealth has been focused on integrating advanced genomic testing and molecular profiling into our treatment decision-making.
Next-generation sequencing (NGS) technologies now enable highly sensitive assessment of MRD, allowing our clinicians to pair increasingly effective therapies with precise detection and quantification of residual malignant cells. This provides us with deeper insight into disease biology and treatment response, helping to inform both current management and future therapeutic strategies.
Our goal is to leverage our precision diagnostics to individualize care, optimize treatment selection and identify the most appropriate clinical trial opportunities for each patient.
Advancing CAR-T Cell Therapy
Among the most transformative immunotherapy advances in multiple myeloma are chimeric antigen receptor T-cell (CAR-T) therapies. These personalized treatments begin by collecting a patient’s own T cells and genetically engineering them in a specialized laboratory to express receptors that recognize proteins on myeloma cells, most commonly B-cell maturation antigen (BCMA). Once expanded, the engineered cells are infused back into the patient, where they can identify, attack and eliminate cancer cells.
AHCI currently offers both FDA-approved CAR-T therapies for multiple myeloma:
- Ciltacabtagene autoleucel (cilta-cel; Carvykti®)
- Idecabtagene vicleucel (ide-cel; Abecma®)
What makes CAR-T therapy particularly exciting is its potential to achieve deep, durable responses following a single infusion. For many patients, this approach may significantly reduce treatment burden by eliminating the need for continuous therapy while delivering prolonged disease control.
AHCI was the first program in Central Florida to offer Carvykti for patients with relapsed or refractory multiple myeloma, beginning in 2022 shortly after its commercial launch. Clinical data have continued to reinforce the promise of this therapy. In the Phase 3 CARTITUDE-4 trial, which compared Carvykti with physician’s choice of standard therapies in patients with lenalidomide-refractory multiple myeloma who had received one to three prior lines of treatment, Carvykti significantly improved progression-free survival, increasing the rate from 48.6% in the standard-care arm to 75.9%. The therapy also demonstrated superior overall response rates and higher rates of MRD negativity, leading to its FDA approval as a second-line treatment in April 2024.
Building on these results, AHCI is participating in the CARTITUDE-5 Phase 3 clinical trial to evaluate Carvykti’s efficacy and safety as a frontline therapy for newly diagnosed multiple myeloma. We are also preparing to participate in the QUINTESSENTIAL-2 study, which will evaluate arlocabtagene autoleucel (arlo-cel; BMS-986393), a next-generation CAR-T therapy targeting the GPRC5D (G protein-coupled receptor class C group 5 member D) antigen, compared with standard regimens in patients with relapsed or refractory, lenalidomide-exposed multiple myeloma after one to three prior therapies.
While CAR-T therapies can cause adverse effects such as cytokine release syndrome and neurotoxicity, our experience has shown that early recognition and prompt intervention enable these to be effectively managed. We have also worked to expand access to CAR-T therapy by safely administering it in the outpatient setting, reducing the costs and logistical challenges associated with hospitalization while maintaining excellent outcomes.
Looking ahead, we expect continued innovation in CAR-T therapy, including the development of multi-targeted approaches designed to reduce disease escape and improve the durability of response. Through ongoing clinical trial participation, AHCI remains committed to ensuring patients have access to the most advanced cellular therapies available.
While CAR-T therapy represents a major breakthrough, it is not the only immunotherapy reshaping the treatment landscape for multiple myeloma. Bispecific antibodies offer another highly promising approach, harnessing the immune system to target myeloma cells without the individualized manufacturing process required for CAR-T therapy. Their growing role is expanding patients’ access to effective immunotherapy across multiple stages of disease.
How Bispecific Antibodies are Changing the Treatment Landscape
Bispecific antibodies offer a novel means of redirecting a patient's own immune system against malignant plasma cells. Unlike conventional monoclonal antibodies, which recognize a single target, bispecific antibodies are engineered to simultaneously bind two distinct antigens, creating a more precise and active immune attack. One arm targets CD3 on T cells, while the other recognizes a myeloma-associated antigen such as BCMA or GPRC5D.
By bringing T cells and myeloma cells together, bispecific antibodies help the immune system do what it is naturally designed to do: recognize and eliminate abnormal cells. Once these cells are connected, the T cell becomes activated and begins attacking the myeloma cell directly. In many ways, bispecific antibodies act like an immunologic bridge, enabling a more precise and potent anti-cancer response.
Unlike CAR-T cell therapy, bi-specific antibodies are readily available, off-the-shelf immunotherapies, making them faster to deploy, which can reduce delays in care. Delivered as subcutaneous injections, they have demonstrated impressive efficacy even in heavily pretreated patients, making them an increasingly important treatment option.
AT AHCI, we offer access to three FDA-approved bi-specific antibodies. Teclistamab (Tecvayli®) and erlanatamab (Elrexfio®) target BCMA, while talquetamab (Talvey®) targets GPRC5D. The strong clinical outcomes achieved with these therapies are increasing our confidence in this approach and driving efforts to expand their use across earlier lines of treatment.
The Expanding Role of Bispecific Antibodies in Combination Therapy
While bispecific antibodies have demonstrated significant activity as single agents, the field is rapidly moving toward combination strategies that layer targeted therapies, immunotherapies and corticosteroids to attack myeloma through multiple mechanisms simultaneously. Given the complexity of multiple myeloma, multi-drug approaches have the potential to deepen responses, prolong remission and reduce the likelihood of treatment resistance.
The promise of this strategy was highlighted by the Phase 3 MajesTEC-3 trial, published in the New England Journal of Medicine. Patients with one to three prior lines of therapy were randomized to receive either teclistamab plus daratumumab or a standard regimen of daratumumab, dexamethasone and the investigator's choice of pomalidomide or bortezomib. The results were striking.
Estimated 36-month progression-free survival was 83.4% in the teclistamab-daratumumab arm compared with 29.7% in the standard-treatment arm. Complete response rates were also substantially higher, with 81.8% of patients achieving a complete response or better compared with 32.1% in the comparator group. These findings underscore the transformative potential of bispecific antibody-based combinations and represent a giant leap forward in myeloma care.
As with CAR-T cell therapy, success of bispecific antibodies has accelerated their use from fifth-line treatment into earlier stages of disease management. What began as an option for heavily pretreated patients is now being evaluated in second-line therapy and in newly diagnosed patients.
AHCI is currently participating in two of those studies:
- MajesTEC-4 is a multicenter, randomized, open-label Phase 3 study evaluating teclistamab plus lenalidomide, or teclistamab alone, compared with lenalidomide alone as maintenance therapy following autologous stem cell transplantation in patients with newly diagnosed multiple myeloma.
- MajesTEC-7 is evaluating teclistamab plus daratumumab and lenalidomide, as well as talquetamab plus daratumumab and lenalidomide, against the standard combination of daratumumab, lenalidomide, and dexamethasone in newly diagnosed patients.
The rapid evolution of bispecific antibody therapy has fundamentally changed our expectations for what immunotherapy can achieve in multiple myeloma. Yet even as these therapies continue to move into earlier lines of treatment, researchers are already developing next-generation approaches designed to further enhance immune targeting, overcome resistance mechanisms, and improve the depth and durability of response. Among the most promising of these innovations are trispecific antibodies, which build upon the success of bispecific therapies by simultaneously engaging multiple immune and tumor targets.
The Next Frontier: Trispecific Antibodies and Immunomodulatory Drugs
Trispecific therapies are the next evolution in immunotherapy for multiple myeloma. Unlike bispecific antibodies that attach to one target on the cancer cell and one on the T-cell, trispecific antibodies bind to two distinct protein targets on the myeloma cell and one immune cell. This tri-targeting approach is designed to maximize tumor selectivity, limit antigen escape and prevent T-cell exhaustion for more durable responses.
Clinical trials of investigational trispecific therapies are beginning, and at AHCI, we plan on participating in several of these studies soon.
We also have a new combination therapy trial coming soon that will explore a novel type of immunotherapy – an oral cereblon E3 ligase modulator (CELMoD) called mezigdomide – that was designed to work as an immunomodulatory drug and targeted protein degrader. This Phase 1b/2a multicenter, open-label study is designed to determine the recommended dose and schedule along with evaluating the safety and preliminary efficacy of mezigdomide in combination with elranatamab in patients with relapsed and/or refractory multiple myeloma.
While these therapies remain investigational, each new clinical trial expands the options available to our patients and brings us closer to achieving deeper, longer-lasting disease responses.
Redefining What’s Possible for Patients with Multiple Myeloma
Multiple myeloma care is advancing at an extraordinary pace. The emergence of CAR-T therapies, bispecific antibodies, precision diagnostics and next-generation immunotherapies is fundamentally changing what can be achieved. We are reaching milestones that once seemed unattainable: unprecedented response rates, deep MRD-negative remissions, and for some patients, durable disease control without continuous treatment. Most importantly, these innovations are translating into longer remissions, improved quality of life and renewed hope for patients and families.
However, there is more work to do. Looking ahead, AHCI plans to continue pursuing earlier intervention studies, including for high-risk smoldering multiple myeloma, a pre-malignant stage. We are also excited about next-generation cellular therapies and continued expansion of immunotherapy approaches.
At AHCI, we are committed to ensuring our patients have access to these innovations today while helping shape the treatments of tomorrow through clinical research. And every advance brings us closer to a future where multiple myeloma is not simply managed but potentially cured.
