Dr Sborov on the Use of Ide-Cel and Cilta-Cel in Relapsed/Refractory Multiple Myeloma

Douglas W. Sborov, MD, MS, associate professor, Department of Internal Medicine—Division of Hematology and Hematologic Malignancies; director, Hematology Disease Center and Plasma Cell Dyscrasias Program, the University of Utah Huntsman Cancer Institute, discusses the use of CAR T-cell therapy for patients with relapsed/refractory multiple myeloma.

The multiple myeloma treatment paradigm is rapidly evolving, with frequent new approvals shifting treatment algorithms, Sborov begins. Until April 2024, FDA-approved therapies including idecabtagene vicleucel (ide-cel; Abecma), ciltacabtagene autoleucel (cilta-cel; Carvykti), and bispecific antibodies targeting BCMA and GPRC5D were indicated for patients who had received 4 or more prior lines of therapy. Treatment recommendations typically involved 3-drug combination regimens based on patients’ prior treatment refractoriness, Sborov added. However, the expanded indications for ide-cel and cilta-cel have widened the net of patients with myeloma who are eligible for these products, he notes. Cilta-cel is now approved for patients with relapsed/refractory multiple myeloma 

 who are refractory to lenalidomide (Revlimid), and ide-cel is now approved 

for patients who have received 2 prior lines of therapy

. These advancements provide more patients with extended treatment-free intervals, including those requiring indefinite myeloma therapy, according to Sborov.

The incorporation of CAR T-cell therapy into earlier lines of therapy could be beneficial for patients with multiple myeloma, as a less heavily pretreated immune system may target cancer cells more effectively, he explains. In his own clinical practice, Sborov discusses the possibility of receiving earlier-line CAR T-cell therapy with all eligible patients due to the therapy’s transformative potential. The earlier-line indications for these products necessitate re-evaluation of existing myeloma treatment algorithms and drug sequencing in the relapsed/refractory setting, he emphasizes. Efforts to refine treatment sequencing strategies are underway and are leveraging both clinical trial outcomes and real-world data, Sborov adds.

When administering CAR T-cell therapy to patients with myeloma, it is crucial to ensure that treatment plans align with patient expectations, Sborov reports. He discusses the entire treatment process with eligible patients, including the workup, time for leukapheresis, manufacturing wait times, lymphodepleting chemotherapy, and CAR T-cell infusion. He also informs his patients that they are required to remain at the Huntsman Cancer Institute for 30 days post-infusion, where they will undergo extended monitoring following the infusion. Sborov also tells patients about potential unique toxicities that are associated with these therapies.

Patient suitability for CAR T-cell therapy is based on age, fitness, disease progression rate, overall disease status, and alignment with personal life plans—considerations that are similar to those for patients undergoing autologous stem cell transplant, Sborov says. Given the availability of BCMA- and GPRC5D-directed bispecific antibodies in later-line myeloma settings, treatment choices often hinge of patient preference, he concludes.

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Douglas W. Sborov, MD, MS, discusses the use of CAR T-cell therapy in patients with relapsed/refractory multiple myeloma.

Douglas W. Sborov, MD, MS, assistant professor, Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah School of Medicine; director, Multiple Myeloma Program and Division of Hematology Biorepository; member, Huntsman Cancer Institute (HCI) Experimental Therapeutics Program; physician leader, Multiple Myeloma/Bone Marrow Transplant arm, HCI Clinical Trials Office; and member, HCI Protocol Review and Monitoring Committee, Huntsman Translational Scholar, University of Utah Health, discusses supportive care approaches for selinexor (Xpovio)-associated toxicities in multiple myeloma. 

Based on available clinical trial data, the XPO1 inhibitor selinexor is an appropriate treatment option for some patients with relapsed/refractory multiple myeloma; however, it is critical to monitor patients for selinexor-associated toxicities, Sborov says. Common adverse effects observed with the agent include cytopenias, hyponatremia, and gastrointestinal events, such as anorexia, nausea, and diarrhea.

Prophylactic treatment during the initial cycles of selinexor administration could include ondansetron (Zofran) on up to day 2 after dosing, olanzapine (Zyprexa) dosed at night, and NK-1 receptor antagonists, Sborov explains. Additionally, encouraging patients to maintain adequate hydration is important, but weekly monitoring for intravenous fluid intervention is also critical. 

Finally, G-CSF or TPO receptor agonists can be considered in patients with significant cytopenias to maintain adequate counts that allow for continued treatment with selinexor, Sborov concludes. 

Douglas W. Sborov, MD, MS, discusses supportive care approaches for selinexor-associated toxicities in multiple myeloma.  



Dr. Sborov on Supportive Care Approaches to Selinexor-Associated Toxicities in Multiple Myeloma 

Douglas W. Sborov, MD, MS, assistant professor, Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah School of Medicine; director, Multiple Myeloma Program and Division of Hematology Biorepository; member, Huntsman Cancer Institute (HCI) Experimental Therapeutics Program; physician leader, Multiple Myeloma/Bone Marrow Transplant arm, HCI Clinical Trials Office; and member, HCI Protocol Review and Monitoring Committee, Huntsman Translational Scholar, University of Utah Health, discusses management strategies for bispecific antibody–related adverse effects in multiple myeloma.

Low-grade cytokine release syndrome (CRS) is one of the main toxicities associated with bispecific antibodies, Sborov says. Early intervention with tocilizumab (Actemra) was met with hesitation initially because it was unknown whether it would negatively affect the efficacy of bispecific antibodies. However, the field now intervenes with tocilizumab even at the onset of grade 1 CRS, which improves the tolerability of the bispecific agent and does not decrease efficacy, Sborov explains. 

However, given the COVID-19 pandemic, many institutions are experiencing a shortage with tocilizumab, which is pushing the field to evaluate other CRS management strategies, such as siltuximab (Sylvant) and anakinra (Kineret), Sborov says.

Douglas W. Sborov, MD, MS, discusses management strategies for bispecific antibody–related adverse effects in multiple myeloma.  



Dr. Sborov on Managing Bispecific Antibody–Related Adverse Effects in Multiple Myeloma 

Douglas W. Sborov, MD, MS, assistant professor, Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah School of Medicine; director, Multiple Myeloma Program and Division of Hematology Biorepository; member, Huntsman Cancer Institute (HCI) Experimental Therapeutics Program; physician leader, Multiple Myeloma/Bone Marrow Transplant arm, HCI Clinical Trials Office; and member, HCI Protocol Review and Monitoring Committee, Huntsman Translational Scholar, University of Utah Health, discusses mitigating toxicities associated with monoclonal antibodies in multiple myeloma.

When utilizing monoclonal antibodies, supportive care measures include prophylactic antivirals, such as acyclovir, given at 400 mg twice daily, Sborov says. Heavily pretreated patients with low absolute lymphocyte counts should be considered for prophylactic antiviral treatment with levofloxacin and trimethoprim/sulfamethoxazole. Additionally, because hepatitis reactivation is a risk in multiple myeloma, checking for hepatitis B and C prior to any treatment is important, Sborov explains.

Additionally, mitigating potential infusion-related reactions with monoclonal antibodies is important and can be done with pretreatment consisting of acetaminophen, diphenhydramine, and an H2 blocker, like clonidine, Sborov adds. Dexamethasone should also be included in the pretreatment regimen, but most patients are receiving the agent as part of their initial treatment regimen.

Regarding daratumumab (Darzalex), patients receive montelukast as supportive care, but the H2 blocker is likely not needed, Sborov says. As subcutaneous daratumumab becomes more utilized vs intravenous daratumumab, the field will continue to refine how long patients need to be monitored for infusion-related reactions following treatment, Sborov concludes.

Douglas W. Sborov, MD, MS, discusses mitigating toxicities associated with monoclonal antibodies in multiple myeloma.  



Dr. Sborov on Mitigating Monoclonal Antibody–Associated Toxicities in Multiple Myeloma 

Douglas W. Sborov, MD, MS, assistant professor, Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah School of Medicine; director, Multiple Myeloma Program and Division of Hematology Biorepository; member, Huntsman Cancer Institute (HCI) Experimental Therapeutics Program; physician leader, Multiple Myeloma/Bone Marrow Transplant arm, HCI Clinical Trials Office; and member, HCI Protocol Review and Monitoring Committee, Huntsman Translational Scholar, University of Utah Health, discusses the toxicities associated with novel therapies in multiple myeloma. 

Although the treatment of patients with multiple myeloma continues to improve with the integration of multiple novel therapies, each regimen is associated with toxicities, Sborov says. Some toxicities, such as cytopenias, infections, and gastrointestinal toxicities, overlap with many available therapies in this paradigm. However, some of the newer therapies offered to patients are associated with unique adverse effects, Sborov explains.

For example, infusion-related reactions are reported in up to 50% of patients treated with CD38-directed monoclonal antibodies, such as daratumumab (Darzalex) and isatuximab-irfc (Sarclisa), and the SLAM7-directed monoclonal antibody elotuzumab (Empliciti), Sborov says. The integration of subcutaneous daratumumab (Darzalex Faspro) has significantly decreased the rate of infusion-related reactions observed with the intravenous formulation, although toxicity remains a risk—particularly during the first 2 doses. 

Novel bispecific antibodies are associated with prominent and consistent low-grade cytokine release syndrome (CRS), Sborov says. As with the monoclonal antibodies, utilizing a subcutaneous formulation of these agents or a step-up dosing strategy could mitigate this toxicity for patients.

Finally, the field is working to develop a better understanding of how to mitigate CAR T-cell therapy–related CRS and immune effort cell–associated neurotoxicity syndrome, Sborov concludes.

Douglas W. Sborov, MD, MS, discusses the toxicities associated with novel therapies in multiple myeloma.  



Douglas W. Sborov, MD, MS

Articles

Dr Sborov on the Use of Ide-Cel and Cilta-Cel in Relapsed/Refractory Multiple Myeloma

Dr. Sborov on Supportive Care Approaches to Selinexor-Associated Toxicities in Multiple Myeloma

Dr. Sborov on Managing Bispecific Antibody–Related Adverse Effects in Multiple Myeloma

Dr. Sborov on Mitigating Monoclonal Antibody–Associated Toxicities in Multiple Myeloma

Dr. Sborov on the Toxicities Associated With Novel Therapies in Multiple Myeloma