Muhamed Baljevic, MD, FACP and Jorge Cortes, MD, discuss upcoming studies and emerging data being presented at the 2024 ASH Annual Meeting.

I look forward to seeing the [data for] single-agent daratumumab in smouldering multiple myeloma, with long-term follow-up results. I have the privilege of presenting a couple of different abstracts with some colleagues around the country.”

Muhamed Baljevic, MD, FACP, hematologist, medical oncologist; associate professor, medicine, Division of Hematology Oncology; director, Plasma Cell Disorders Research; director, Vanderbilt Amyloidosis Multidisciplinary Program, Vanderbilt-Ingram Cancer Center, shares key studies in multiple myeloma that will be presented at the 2024 ASH Annual Meeting.

Among these highly-anticipated trials is the randomized, phase 3 AQUILA study (NCT03301220), which evaluated daratumumab (Darzalex) monotherapy vs active monitoring in patients with high-risk smoldering multiple myeloma. Primary results from the study are expected to inform future management strategies in this patient population. These long-term follow-up data are crucial for understanding the efficacy of single-agent daratumumab in delaying disease progression, Baljevic emphasizes.

Baljevic will also present updated results from the phase 1b/2 STOMP trial (NCT02343042). The dataset will comprise cohorts that received weekly 40 mg or 60 mg doses of selinexor (Xpovio) plus pomalidomide (Pomalyst) and dexamethasone.

We are going to be presenting an update at the 2024 ASH Annual Meeting. We're going to be presenting the 96 weeks data. That's going to be very important in terms of efficacy and safety.

Jorge Cortes, MD, director of the Georgia Cancer Center at Augusta University, also previewed the 96-week data update from the phase 3 ASC4FIRST trial (NCT04971226) evaluating asciminib (Scemblix) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP).

This update, which will be presented at the meeting, will focus on the efficacy and safety of asciminib compared with investigator-selected TKIs as frontline therapy.

On October 29, 2024, the FDA granted accelerated approval to asciminib, a first-in-class STAMP inhibitor targeting the ABL myristoyl pocket, based on data from the phase 3 ASC4FIRST trial. Previously reported data from the study showed that patients treated with asciminib (n = 201) experienced a 48-week major molecular response (MMR) rate of 68% (95% CI, 61%-74%) vs 49% (95% CI, 42%-56%) in those treated with investigator’s choice of TKI (n = 204). These included imatinib (Gleevec), nilotinib (Tasigna), dasatinib (Sprycel), or bosutinib (Bosulif; difference, 19%; 95% CI, 10%-28%; P < .001).

Cortes notes that this update will provide insights into the long-term efficacy and safety profile of asciminib as a frontline therapy for newly diagnosed CML-CP. He concludes that the FDA approval of asciminib represents a pivotal step towards improving patient outcomes and cure rates for this disease.

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Drs Baljevic and Cortes Preview Upcoming Studies and Emerging Data From ASH 2024

, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, 

 covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, we had the pleasure of speaking with Binod Dhakal, MD, and Muhamed Baljevic, MD, about updates regarding patient identification for optimal multiple myeloma treatment. Dr Dhakal is an associate professor of medicine in the Division of Hematology at the Medical College of Wisconsin in Milwaukee. Dr Baljevic is an associate professor of medicine in the Division of Hematology Oncology, director of Plasma Cell Disorders Research, director of the Vanderbilt Amyloidosis Multidisciplinary Program, co-chair of the Protocol Review and Monitoring System, and disease team lead for plasma cell dyscrasias and lymphomas at the Vanderbilt-Ingram Cancer Center, part of the Vanderbilt University Medical Center in Nashville, Tennessee. 

In our exclusive interview, Drs Dhakal and Baljevic discussed first- and subsequent-line treatment options for patients with multiple myeloma, treatment options beyond CAR T-cell therapy for unfit patients, and ongoing research that may expand the myeloma treatment paradigm in the future.

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Drs Dhakal and Baljevic discuss first- and subsequent-line treatment options for patients with multiple myeloma. 

How to Optimize Patient Selection for Multiple Myeloma Therapies: With Binod Dhakal, MD; and Muhamed Baljevic, MD

Dr Baljevic on the PERSEUS Trial in Untreated Multiple Myeloma

Muhamed Baljevic, MD, FACP, hematologist, medical oncologist, associate professor, medicine, Division of Hematology Oncology, director, Plasma Cell Disorders Research, director, Vanderbilt Amyloidosis Multidisciplinary Program, Vanderbilt-Ingram Cancer Center; co-chair, the Vanderbilt-Ingram Cancer Center Protocol Review and Monitoring System, discusses the phase 3 PERSEUS trial (NCT03710603) in patients with previously untreated multiple myeloma.

The PERSEUS trial examined daratumumab (Darzalex) followed by autologous stem cell transplant (ASCT) and daratumumab, bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (D-VRd), Baljevic begins. A unique aspect of the PERSEUS trial design was that patients who achieved sustained minimal residual disease (MRD) negativity for 12 months, following at least 2 years of maintenance with daratumumab, were allowed to discontinue daratumumab and continue with lenalidomide alone, he reports. If these patients lost their MRD-negative status or complete response, they had the option to restart daratumumab. This feature of the trial is particularly significant because it reflects the current trend toward developing more refined and potentially less intensive treatment strategies, Baljevic states.

An important takeaway regarding quadruplet therapies, which are the standard of care in North America for patients with treatment-naive multiple myeloma, is their limited global accessibility due to high costs, according to Baljevic. Although costs are a crucial consideration, the PERSEUS trial still demonstrated positive efficacy outcomes, showing a comparative PFS benefit with the quadruplet therapy over triplet therapy with VRd induction and consolidation followed by maintenance with lenalidomide alone after a median follow-up of 47.5 months, Baljevic explains.

Another valuable aspect of the PERSEUS trial is the data on sustained MRD negativity after at least 12 months, he continues. These data are significant as they align with the 

FDA’s Oncologic Drugs Advisory Committee's emphasis on MRD

 as a crucial end point in multiple myeloma, Baljevic notes. The trial revealed that approximately 64% of patients in the D-VRd group discontinued daratumumab after achieving sustained MRD negativity, highlighting the potential for de-escalating treatment, Baljevic says.

This trial provides critical data to guide clinical decisions, Baljevic emphasizes. It raises essential questions about when and to what extent oncologists can safely reduce therapy in patients with multiple myeloma, he explains. Understanding when to de-escalate therapy, the appropriate steps for maintenance, and the circumstances under which therapy should be resumed are all vital considerations, Baljevic concludes.

Muhamed Baljevic, MD, FACP, discusses the phase 3 PERSEUS trial in patients with previously untreated multiple myeloma.

Muhamed Baljevic, MD, discusses the consideration of patient comorbidities and preferences during treatment selection in newly diagnosed myeloma.

Dr Baljevic on Key Considerations for Treatment Selection in Newly Diagnosed Multiple Myeloma

Muhamed Baljevic, MD, FACP, hematologist and medical oncologist,associate professor of medicine, Division of Hematology Oncology; director, Plasma Cell Disorders Research of Vanderbilt-Ingram Cancer Center; director, Vanderbilt Amyloidosis Multidisciplinary Program, Vanderbilt-Ingram Cancer Center; co-chair, VICC Protocol Review and Monitoring System, discusses patient comorbidities and preferences to take into consideration when determining personalized treatment approaches in newly diagnosed multiple myeloma. Baljevic expanded on these topics in his presentation at the Vanderbilt Stem Cell Transplant and Cellular Therapy Symposium.

In the era of personalized medicine, understanding patient comorbidities and factors influencing therapy choice is paramount, Baljevic begins, emphasizing that considering patient preferences and their logistical capabilities for therapy delivery is crucial. The COVID-19 pandemic has significantly altered approaches to patient care, including therapeutic choices and administration methods. Although the primary goal of treatment is still to deliver effective therapeutics, individual perceptions of quality of life and treatment priorities can vary, he states.

Currently, quadruplet regimens are the standard of care (SOC) for the management of newly diagnosed multiple myeloma, Baljevic continues. The phase 2 GRIFFIN study (NCT02874742), which evaluated the addition of daratumumab (Darzalex) to the combination of lenalidomide (Revlimid), dexamethasone, and bortezomib (Velcade; D-RVd) plus autologous stem cell transplant (ASCT), has shown promising long-term follow-up results, he says. Specifically, the study reported a significantly better 4-year progression-free survival (PFS) with the quadruplet regimen compared with RVd alone, although PFS was not the primary end point of the GRIFFIN study, Baljevic states.

Despite the lack of difference in overall survival between these regimens, there was a notable improvement in the depth of responses over time, Baljevic reports. From the end of induction through post-transplant consolidation, and even to the final analysis, both the triplet and quadruplets demonstrated continued deepening and improving responses. However, the quadruplet regimen showed a greater ability to induce deep minimal residual disease (MRD) responses, Baljevic notes.

The evolving landscape of multiple myeloma treatment underscores the importance of personalized approaches that balance efficacy, patient preferences, and logistical considerations, Baljevic concludes.

Muhamed Baljevic, MD, discusses key trial updates and advancements with quadruplet therapy in newly diagnosed multiple myeloma.

Dr Baljevic on Advancements in the Management of Newly Diagnosed Multiple Myeloma

Muhamed Baljevic, MD, associate professor of medicine, Division of Hematology Oncology; director, Plasma Cell Disorders Research of Vanderbilt-Ingram Cancer Center; director, Vanderbilt Amyloidosis Multidisciplinary Program, Vanderbilt-Ingram Cancer Center; co-chair, VICC Protocol Review and Monitoring System, discusses key trial updates and advancements with quadruplet therapy in newly diagnosed multiple myeloma, as detailed in his presentation at the Vanderbilt Stem Cell Transplant and Cellular Therapy Symposium.

Over the past decade, progress has been made in achieving deep and durable responses to treatment in newly diagnosed multiple myeloma patients, Baljevic begins. Trials such as the phase 2 GRIFFIN study (NCT02874742) have explored the use of quadruplet induction therapy for patients in this population, he states, adding that these regimens typically comprise a proteasome inhibitor, an immunomodulatory drug, an anti-CD38 monoclonal antibody, and a steroid. Results from these trials have demonstrated substantial improvements in time to first progression-free survival (PFS), with median PFS extending from approximately 40 months to as long as 90 months, Baljevic details. Moreover, in some trials, the median PFS has not yet been reached due to sustained responses, he notes.

Placing emphasis on achieving optimal patient outcomes early in the disease course is particularly crucial in the management of multiple myeloma, Baljevic continues. Studies such as the Intergroupe Francophone du Myelome 2009 (NCT01191060) and phase 3 DETERMINATION (NCT01208662) trials have highlighted the importance of optimal upfront treatment; not all patients have the opportunity to undergo stem cell transplantation later in their disease course, Baljevic emphasizes.

Moreover, significant attrition has been observed in select datasets of non-transplant eligible patients, underscoring the urgency of initiating effective treatments to maximize long-term outcomes, Baljevic says. Ultimately, early intervention and achieving deep responses with novel combinations are critical steps towards optimizing the management of newly diagnosed myeloma, he concludes.

Muhamed Baljevic, MD, assistant professor, Department of Internal Medicine, Division of Oncology and Hematology, College of Medicine, University of Nebraska Medical Center, discusses the current limitations of CAR T-cell therapy in multiple myeloma.

In the clinical trials evaluating CAR T-cell therapy in multiple myeloma, some patients who underwent apheresis and CAR T-cell collection were unable to receive the treatment because their disease was too aggressive and dynamic, Baljevic says. Even with bridging therapy, these patients were unable to wait the 4 to 5 weeks required to generate the CAR T-cell therapy.

Additionally, a significantly number of patients were not referred for CAR T-cell therapy because they lived too far away from an academic center that offers the treatment, Baljevic explains. These patients, as well as older patients and those with poor performance statuses, represent a population with unmet need for CAR T-cell therapy in multiple myeloma. 

However, emerging constructs that have been optimized to be potentially safer and more effective could have clinical utility in these patient populations, Baljevic concludes.

Muhamed Baljevic, MD, discusses the current limitations of CAR T-cell therapy in multiple myeloma.  



Dr. Baljevic on the Current Limitations of CAR T-Cell Therapy in Multiple Myeloma 

Muhamed Baljevic, MD, assistant professor, Department of Internal Medicine, Division of Oncology and Hematology, College of Medicine, University of Nebraska Medical Center, discusses the FDA approval of isatuximab-irfc (Sarclisa) in combination with pomalidomide (Pomalyst) and low-dose dexamethasone in relapsed/refractory multiple myeloma. 

In March 2020, the FDA approved isatuximab in combination with pomalidomide and low-dose dexamethasone for the treatment of patients with multiple myeloma who received at least 2 prior therapies, including lenalidomide (Revlimid) and a proteasome inhibitor. The regulatory decision was based on findings from the phase 3 ICARIA-MM trial (NCT02990338), in which the triplet regimen led to a 40% reduction in the risk of disease progression or death compared with pomalidomide and dexamethasone alone in this patient population. 

The approval was significant in that it introduced a novel CD38-directed monoclonal antibody beyond daratumumab (Darzalex) to the paradigm and combined it with pomalidomide, a novel immunomodulatory agent, Baljevic says. The triplet fulfills a significant unmet need for patients with relapsed/refractory multiple myeloma who meet the specific prior therapy requirements needed to receive the regimen, Baljevic concludes.

Muhamed Baljevic, MD, discusses the FDA approval of isatuximab-irfc in combination with pomalidomide and low-dose dexamethasone in relapsed/refractory multiple myeloma.  



Muhamed Baljevic, MD

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