Roberto Mina, MD, Assistant Professor at Winship Cancer Institute at Emory University, discusses results from the MajesTEC-9 and CARTITUDE-4 clinical trials in patients with relapsed/refractory multiple myeloma (RRMM).

MM is a rare blood cancer characterized by the expansion of malignant plasma cells in the bone marrow associated with excessive production of monoclonal immunoglobulins in blood and urine. Individuals with multiple myeloma develop significant osteolytic bone lesions and have immunodeficiency that compromise their longevity and quality of life. The exact underlying cause of disease is currently unknown. Most patients with MM require multiple lines of therapy as patients are prone to relapse and/or refractory to therapy.

CARTITUDE-4 Cytogenetic Subgroup Analysis

CARTITUDE-4 (NCT04181827) is a phase 3 randomized clinical trial comparing Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T Cell (CAR-T) therapy directed against BCMA, versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in patients with relapsed and lenalidomide-refractory MM.

Previous analyses of cilta-cel showed significant overall (OS) and progression-free survival (PFS) benefits of cilta-cel in patients with lenalidomide-refractory MM after 1 to 3 lines of therapy. The data presented at ASCO 2026 looked at the safety and efficacy in patients who received cilta-cel as study treatment with high- and standard-risk cytogenetics who responded to bridging therapy.

Of 176 total patients who received cilta-cel as study treatment, with a median follow-up, of 33.6 months, 64 patients had high-risk cytogenetics and achieved partial response or better to bridging therapy. In these patients, median progression free survival and overall survival were not reached, however, 30-month progression free survival and overall survival rates were 65.1% and 87.2%, respectively. In 40 patients with standard-risk cytogenetics and partial response or better to bridging therapy, median progression free survival and overall survival were not reached, however, 30-month progression free survival and overall survival rates were 85.0% and 92.5%, respectively.

Safety analysis included 64 patients with high-risk and 40 with standard-risk cytogenetics. In the high-risk subgroup, cytokine release syndrome was reported in 73.4% of patients, serious nonhematological adverse events in 64.1%, grade 3/4 infections in 43.8%, and immune effector cell-associated neurotoxicity syndrome in 7.8%. Corresponding rates in the standard-risk subgroup were 70.0%, 57.5%, 30.0%, and 0. Nonrelapse mortality occurred in 9 patients and there were 4 infection-related deaths in the high-risk population. No cases of immune effector cell (IEC)-parkinsonism were reported in either subgroup.

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Roberto Mina, MD, Assistant Professor at Winship Cancer Institute at Emory University, discusses results from the MajesTEC-9 and CARTITUDE-4 clinical trials in patients with relapsed/refractory multiple myeloma (RRMM).

MM is a rare blood cancer characterized by the expansion of malignant plasma cells in the bone marrow associated with excessive production of monoclonal immunoglobulins in blood and urine. Individuals with multiple myeloma develop significant osteolytic bone lesions and have immunodeficiency that compromise their longevity and quality of life. The exact underlying cause of disease is currently unknown. Most patients with MM require multiple lines of therapy as patients are prone to relapse and/or refractory to therapy.

MajesTEC‑9 Phase 3 Results

MajesTEC-9 (NCT05572515) is a phase 3 randomized clinical trial comparing teclistamab monotherapy, a bispecific T-cell engager (BiTe) antibody, versus pomalidomide, bortezomib, dexamethasone (PVd) or carfilzomib, dexamethasone (Kd) in patients with relapsed or refractory MM who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide.

A total of 593 patients were randomized and had a median follow-up of 17.3 months. Teclistamab was observed to significantly improve both progression free survival and overall survival versus PVd/Kd. Of 174 patients treated with PVd/Kd who received subsequent treatment, 68.4% received BsAb or CAR-T. Progression free survival favored teclistamab across all prespecified subgroups, including anti-CD38-refractory patients and len-refractory patients. Complete response or better rate was significantly higher with teclistamab versus PVd/Kd.

At data cutoff, 65.3% of patients remained on teclistamab versus 24.0% on PVd/Kd. Treatment emergent adverse events were similar for teclistamab and PVd/Kd. Grade 3/4 adverse events (84.9% vs 76.3%) and grade 5 adverse events (6.5% vs 3.5%) were higher with teclistamab vs PVd/Kd, noting the median treatment duration was 13.1 months with teclistamab 7.0 months with PVd/Kd. Treatment discontinuation lower with teclistamab versuss PVd/Kd. CRS occurred in 66.0% of pts with teclistamab and ICANS in 4.1%.

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Roberto Mina, MD, Assistant Professor at Winship Cancer Institute at Emory University, discusses results from the MajesTEC-9 and CARTITUDE-4 clinical trials in patients with relapsed/refractory multiple myeloma (RRMM).

MM is a rare blood cancer characterized by the expansion of malignant plasma cells in the bone marrow associated with excessive production of monoclonal immunoglobulins in blood and urine. Individuals with multiple myeloma develop significant osteolytic bone lesions and have immunodeficiency that compromise their longevity and quality of life. The exact underlying cause of disease is currently unknown. Most patients with MM require multiple lines of therapy as patients are prone to relapse and/or refractory to therapy.

MajesTEC‑9 Phase 3 Results

MajesTEC-9 (NCT05572515) is a phase 3 randomized clinical trial comparing teclistamab monotherapy, a bispecific T-cell engager (BiTe) antibody, versus pomalidomide, bortezomib, dexamethasone (PVd) or carfilzomib, dexamethasone (Kd) in patients with relapsed or refractory MM who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide.

A total of 593 patients were randomized and had a median follow-up of 17.3 months. Teclistamab was observed to significantly improve both progression free survival and overall survival versus PVd/Kd. Of 174 patients treated with PVd/Kd who received subsequent treatment, 68.4% received BsAb or CAR-T. Progression free survival favored teclistamab across all prespecified subgroups, including anti-CD38-refractory patients and len-refractory patients. Complete response or better rate was significantly higher with teclistamab versus PVd/Kd.

At data cutoff, 65.3% of patients remained on teclistamab versus 24.0% on PVd/Kd. Treatment emergent adverse events were similar for teclistamab and PVd/Kd. Grade 3/4 adverse events (84.9% vs 76.3%) and grade 5 adverse events (6.5% vs 3.5%) were higher with teclistamab vs PVd/Kd, noting the median treatment duration was 13.1 months with teclistamab 7.0 months with PVd/Kd. Treatment discontinuation lower with teclistamab versuss PVd/Kd. CRS occurred in 66.0% of pts with teclistamab (Gr and ICANS in 4.1%.

CARTITUDE-4 Cytogenetic Subgroup Analysis
CARTITUDE-4 (NCT04181827) is a phase 3 randomized clinical trial comparing Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T Cell (CAR-T) therapy directed against BCMA, versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in patients with relapsed and lenalidomide-refractory MM.

Previous analyses of cilta-cel showed significant overall (OS) and progression-free survival (PFS) benefits of cilta-cel in patients with lenalidomide-refractory MM after 1 to 3 lines of therapy. The data presented at ASCO 2026 looked at the safety and efficacy in patients who received cilta-cel as study treatment with high- and standard-risk cytogenetics who responded to bridging therapy.

Of 176 total patients who received cilta-cel as study treatment, with a median follow-up, of 33.6 months, 64 patients had high-risk cytogenetics and achieved partial response or better to bridging therapy. In these patients, median progression free survival and overall survival were not reached, however, 30-month progression free survival and overall survival rates were 65.1% and 87.2%, respectively. In 40 patients with standard-risk cytogenetics and partial response or better to bridging therapy, median progression free survival and overall survival were not reached, however, 30-month progression free survival and overall survival rates were 85.0% and 92.5%, respectively.

Safety analysis included 64 patients with high-risk and 40 with standard-risk cytogenetics. In the high-risk subgroup, cytokine release syndrome was reported in 73.4% of patients, serious nonhematological adverse events in 64.1%, grade 3/4 infections in 43.8%, and immune effector cell-associated neurotoxicity syndrome in 7.8%. Corresponding rates in the standard-risk subgroup were 70.0%, 57.5%, 30.0%, and 0. Nonrelapse mortality occurred in 9 patients and there were 4 infection-related deaths in the high-risk population. No cases of immune effector cell (IEC)-parkinsonism were reported in either subgroup.

CHAPTERS
Introduction 00:00
Unmet Needs in Multiple Myeloma 00:31
MajesTEC-9 Clinical Trial 2:04
CARTITUDE-4 Clinical Trial 5:12
T-Cell Directed Therapies in the Treatment Journey 7:26
Impact on Clinical Practice and Patient Outcomes 8:46

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David Kuter, MD, DPhil, Director of Clinical Hematology at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, discusses cognitive impairment in patients with immune thrombocytopenia (ITP).

ITP is an autoimmune bleeding disorder characterized by too few platelets in the blood. Symptoms may include bruising, nosebleeds or bleeding in the mouth, bleeding into the skin, and abnormally heavy menstruation. It has been traditionally managed with corticosteroids, medicines that stimulate the bone marrow to increase platelets, and immunoglobulin infusions to restore critically low platelet counts.

Data presented at the European Hematology Association (EHA) 2026 meeting highlights that focusing on platelet counts alone does not fully capture the disease burden of ITP. The objective of the study was to determine the frequency, nature, and severity of cognitive impairment in chronic primary ITP in a real-world setting.

Of 104 patients screened, 97 were eligible to participate in the study and completed the Cognitive Brief Battery (CBB) test, a validated test evaluating psychomotor function, visual attention, visual learning, and visual working memory. The median duration of ITP was 10 years. 82 patients reported receiving active ITP treatment at index, including TPO-RAs, corticosteroids, other immunosuppressants, fostamatinib, rituximab, and/or other. Median platelet count was 143×109/L and median hemoglobin was 139 g/L. 80 participants had comorbidities, including arterial hypertension, anxiety, obesity, depression, and hypercholesterolemia. The mean ITP bleeding scale total score was 0.04 and mean scores for FACIT-Fatigue, ITP-PAQ psychological health (PH), and ITP-PAQ overall QOL were 37, 76, and 65, respectively.

Clinically important cognitive impairment was observed in 26% of patients, with 68% aged less than 65 years. Among the 97 patients evaluated, 7 patients, ages 39-78 years, had z-score of less than or equal to -1 for both composite scores; 12 patients, aged 25-75 years, had z-score of less than or equal to -1 for learning/working memory only, and 6 patients, aged 25-80 years, had z-scores of less than or equal to -1 for psychomotor function/attention only.

Overall, the analyses showed that patients continue to experience persistent fatigue and cognitive impairment even with stable platelet counts. This highlights the need for more comprehensive disease management in ITP that focuses more on a patient's quality of life beyond hematologic lab results.

CHAPTERS
Introduction 00:00
Looking Beyond Platelet Counts 00:51
Cognitive Impairments in ITP 2:15
Fatigue in ITP 3:35
Underlying Immune Dysfunction 5:09
Better Assessment of These Symptoms 6:32
Comprehensive Disease Control 7:44

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Joanne Quan, MD, Chief Medical Officer of Mirum Pharmaceuticals, discusses results from the PROGRESS study of zilurgisertib in patients with fibrodysplasia ossificans progressiva (FOP).

FOP is a disorder in which skeletal muscle and connective tissue are gradually ossified. This condition leads to bone formation outside the skeleton that restricts movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and moving down the body and into the limbs. People with FOP are born with abnormal big toes which can be helpful in making the diagnosis. Trauma, such as a fall or invasive medical procedure, or a viral illness may trigger episodes of muscle swelling and inflammation. These flareups last for several days to months and often result in permanent bone growth in the injured area. FOP is almost always caused by a genetic change at the same place in the ACVR1 gene.

Phase 2 results from Cohort 1 of the PROGRESS study (NCT05090891) evaluating zilurgisertib in adolescents and adults with FOP were presented at the ENDO 2026 annual meeting. Zilurgisertib is an investigational oral activin receptor-like kinase 2 (ALK2) inhibitor.

Of 63 patients who received one dose of zilurgisertib (n = 32) or placebo (n = 31), 62 enrolled in the extension. The primary endpoint was the proportion of patients with new heterotopic ossification (HO) lesions on whole-body CT scan at week 24.

At week 24, there was an 81.2% reduction in patients with new lesions receiving zilurgisertib versus 16.7% receiving placebo. Total new lesion volume decreased by 99.6% with zilurgisertib, while placebo was associated with a marked increase. The mean annualized total number of new flares was also lower for zilurgisertib.

In the open-label period, no new lesions were reported regardless of treatment assignment. From week 24-48, mean decreases in total volume of all HO lesions were observed in both zilurgisertib-randomized and crossover patients. The mean number of annualized new flares was low for both patient groups.

The most common adverse events in the zilurgisertib group were FOP flare-up or aching/pain due to FOP, headache, upper respiratory tract infection, arthralgia, epistaxis, and nausea, with a similar profile in the extension. Most adverse events were mild or moderate and none led to dose reduction or discontinuation with zilurgisertib across both periods.

CHAPTERS
Introduction 00:00
FOP Overview 00:10
Zilurgisertib Overview 1:38
PROGRESS Clinical Trial 2:24
What Physicians Should Know 6:05

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Robert Hal Scofield, MD, Professor of Medicine, at the University of Oklahoma and Oklahoma Medical Research Foundation, discusses the DAHLIAS clinical trial evaluating nipocalimab in Sjögren’s disease (SjD).

SjD is an autoimmune disorder that largely impacts secretory glands, such as those that produce tears and saliva. It is also associated with rheumatic disorders such as rheumatoid arthritis or systemic lupus erythematosus. Hallmark symptoms include dry mouth and dry eyes, but the condition may cause skin, nose, and vaginal dryness. SjD may also affect other organs of the body including the kidneys, blood vessels, lungs, liver, pancreas, and brain.

Nipocalimab is a monoclonal antibody, designed to block FcRn and reduce levels of circulating IgG antibodies. It is currently approved for the treatment of generalized myasthenia gravis.


At the European Alliance of Associations for Rheumatology (EULAR) 2026 Congress new biomarker exploratory analyses from the DAHLIAS phase 2 study (NCT04968912) evaluating nipocalimab in SjD was presented.

Results included clinical improvements observed across all patients. The most significant responses were observed in patients with elevated known disease-driving autoantibodies and IgG levels. Patients in the autoantibody-high subgroup who were treated with nipocalimab achieved higher response rates than the overall population, at 62.5% versus 51.9%. Previously reported results demonstrated statistically significant improvement in ClinESSDAI scores with nipocalimab versus placebo.

Nipocalimab is being further evaluated in patients with systemic SjD in the ongoing DAFFODIL phase 3 clinical trial (NCT06741969).

CHAPTERS
Introduction 00:00
Sjögren’s Disease Overview 00:53
Key Findings From DAHLIAS Clinical Trial 2:01
Stronger Responses in Autoantibody Subgroups 3:34
Identifying Patients Who Will Benefit 4:48
Next Steps 5:22
Take Home Message 6:46

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H. Miles Prince, MD, MBBS, Professor at the University of Melbourne, Australia, and Director, Peter MacCallum Cancer Center, and Director of Molecular Oncology and Cancer Immunology, Epworth HealthCare describes the objectives and results of a new investigation which studied the previous results from the MAVORIC trial in patients with cutaneous T-cell lymphoma with those of patients in an Australian cancer registry.

The mogamulizumab versus vorinostat therapy in previously treated cutaneous T-cell lymphoma (MAVORIC) trial sought to compare the efficacy of the monoclonal antibody mogamulizumab against the standard of care (vorinostat) in patients with mycosis fungoides or Sézary syndrome, which together comprise cutaneous T-cell lymphoma (CTCL).

Patients were eligible if they had failed at least one previous systemic therapy. They were randomized to one of two treatment arms: mogamulizumab or vorinostat. Researchers found that the study was superior in terms of the main clinical endpoint of the study—progression-free survival (PFS) (7.7 mo vs. 3.1 mo; hazard ratio = 0.53; P less than .0001).

The study also included a crossover arm for patients who could not tolerate vorinostat or whose disease progressed. Total overall survival (OS) for the intent-to-treat population taking mogamulizumab was just less than 5 years, but the difference from the comparator group was not statistically significant, possibly due to the crossover arm, according to Dr. Prince. Yet, the regulatory authorities of several countries, including those in northern Europe and Australia, require OS as primary clinical endpoint when seeking market authorization.

To determine whether mogamulizumab exhibited a true OS benefit, his team of researchers evaluated an Australian cancer registry, seeking patients who took vorinostat and who fulfilled MAVORIC study inclusion criteria. Matched to those in the study arm of MAVORIC, they were able to confirm a distinct improvement in OS in those taking mogamulizumab.

The results of this research help fulfill the OS data requirements for regulatory approval of mogamulizumab, but it also raises questions as to whether it should be used first line, especially in patients with aggressive forms of CTCL. Furthermore, it might be interesting to consider mogamulizumab as a foundation for drug combinations in managing this difficult-to-treat cancer.

CHAPTERS
Introduction 00:00
Mogamulizumab Clinical Trial 00:35
Role in Relapsed/Refractory Mycosis Fungoides and Sézary Syndrome 3:24
Influencing Treatment Decisions and Research Efforts 4:53
Regulatory Impact 6:43

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Lena Specht, MD, DMSc, Professor of Clinical Oncology, and Chief Oncologist at Rigshopitalet, University of Copenhagen, Denmark, discusses her Danish study supporting the use of mogamulizumab in Danish patients with CTCL.

Mogamulizumab was approved in 2018 in Europe based on the results of the MAVORIC trial, which was a randomized study comparing progression-free survival outcomes against vorinostat, an FDA-approved treatment, in patients with CTCL.

Vorinostat was never approved in Europe, because it was associated with data issues and was not considered a valid study comparator. As a result, the Danish regulatory authorities approved mogamulizumab for use only after a trial of one prior line of systemic chemotherapy. In comparison, the US FDA approved mogamulizumab for use as first-line treatment of CTCL.

Dr. Specht’s group of researchers attempted to compare the randomized phase 3 trial comparing mogamulizumab and the Danish standard of care by utilizing the MAVORIC study data along with data from a real-world registry of Danish patients with CTCL from 1996 to 2024. They selected comparator patients from the registry according to MAVORIC inclusion criteria (including patients with either myocosis fungoides or Sézary syndrome who failed at least one line of systemic therapy). In addition, they evaluated data from the vorinostat arm in MAVORIC (i.e., those patients who did not switch over to mogamulizumab therapy).

The main outcome of interest was overall survival. They found overall survival to be longer (with a statistically significant difference) for those receiving mogamulizumab first line compared with the Danish patients with CTCL in the real-world registry. Although making treatment comparisons using nonrandomized patient data is problematic, Dr. Specht and her researchers were reassured that there was not any significant difference in the outcomes of those in the vorinostat treatment arm of MAVORIC and in the Danish registry population receiving standard of care.

Normally, Sézary syndrome is very difficult to treat, but mogamulizumab seems to work better in these patients than in those with mycosis fungoides, which is generally considered a less-aggressive cancer. According to Dr. Specht, this is a strong argument for first-line access to mogamulizumab in patients with Sézary syndrome.

CHAPTERS
Introduction 00:00
Mogamulizumab Clinical Trial 00:58
Key Findings in Overall Survival 3:15
Patient Subgroup Analysis 4:29
Key Takeaway 6:11

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Christiane Querfeld, MD, PhD, dermatologist and and Director, Multidisciplinary Cutaneous Lymphoma Program, Professor at the City of Hope National Medical Center and the Beckman Research Institute, discusses the results of a new drug trial that increased the dosing interval of mogamulizumab in patients with CTCL.

Currently, treatment with the oncolytic agent mogamulizumab-kpkc (Poteligeo) in patients with Sézary syndrome and mycosis fungoides, which is collectively called cutaneous T-cell lymphoma (CTCL), consists of weekly infusions during the first month of therapy, followed by double doses administered twice monthly. A new trial, called the MOGA-2 mg q4w study, sought to evaluate the effectiveness and safety of mogamulizumab given by weekly infusions for the first month, followed by once monthly injections of 2-mg doses, for each subsequent month.

Another aspect of the study is to gather data around the appearance of a rash that is associated with mogamulizumab use. This seems to be an indication of an “immune flare,” which varies in severity by patient but can be debilitated in those most affected. Dr. Querfeld pointed out that the rash is more common in patients who respond to mogamulizumab therapy than those with do not.

By reducing the number of infusions, this may improve patient’s quality of life and lessen the transportation burden on patients and their caregivers. The key, according to Dr. Querfeld, is using the data obtained from the study to determine if certain subgroups of patients respond favorably to this regimen. She hopes these cohorts may be identified by their gene signatures, or classifications of variants in multiple genes.

Currently, 65 gene mutations have been identified as drivers of CTCL. The trial found that patients who responded well to the modified mogamulizumab regimen had more mutations compared with nonresponders.

It is thus critical for any diagnosed patient to have their skin biopsied and evaluated on a molecular level, identifying gene mutations, and especially CCR4 status. It will allow patients earlier access to personalized, targeted medicine, and perhaps optimally effective treatment.

CHAPTERS
Introduction 00:00
MOGA-2MG-Q4W Clinical Trial 00:39
Determining Patients Most Likely to Benefit 6:31
The Future of Personalized Care 8:18
Key Takeaway for Physicians 9:28
Next Steps 10:52

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