Amandeep Godara, MBBS, a medical oncologist, Huntsman Cancer Institute, assistant professor, Division of Hematology and Hematologic Malignancies, University of Utah, discusses important patient factors to consider when deciding between a CAR T-cell therapy vs bispecific antibody in relapsed/refractory multiple myeloma. Godara also elaborates on the importance of mitigating treatment-related toxicities associated with the administration of bispecific antibodies in this disease setting.

When selecting between CAR T-cell therapy or treatment with a bispecific antibody, whether a patient's relapse can be characterized as aggressive or not should first be addressed, Godara begins. Bispecific antibodies are recommended for the treatment of patients with aggressive relapsed/refractory disease if no other effective therapies are available, Godara states. In this scenario, a bispecific antibody approach could allow patients to begin treatment sooner, thereby increasing the likelihood that they will achieve responses in a shorter period, he explains.

CAR T-cell therapy could also be considered for patients with aggressive relapsed disease, but it may be necessary to use bridging therapies to control the disease during any accompanying delay in product manufacturing, Godara clarifies.

Although bispecific antibodies are a viable option for the treatment of patients with relapsed/refractory myeloma, they are associated with some safety concerns, Godara notes. Opportunistic infections such as pneumocystis, pneumonia, or cytomegalovirus are rarely observed in patients with multiple myeloma, he says. However, bispecific antibodies are linked with a higher incidence of infection in this patient population, Godara says. This risk of infection is further increased with the use of bispecific antibodies in combination with daratumumab (Darzalex) or lenalidomide (Revlimid). Such infections typically occur month to month after treatment initiation, Godara details.

Intensive supportive care measures, such as the administration of anti-microbials or prophylactic intravenous immunoglobulin, can be prescribed to reduce the risk of infection, as well as treatment-related discontinuations or delays, Godara continues.

Therefore, it is important to improve the management of these toxicities before appointing bispecific antibodies as the new standard of care in myeloma treatment, Godara concludes.

Godara reports serving in a consulting or advisory role for X4 Pharma.

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Amandeep Godara, MBBS, discusses important patient factors to consider when deciding between a CAR T-cell therapy vs bispecific antibody in relapsed/refractory multiple myeloma, and the importance of mitigating treatment-related toxicities associated with the administration of bispecific antibodies in this disease setting. 


Dr Godara on the Selection of CAR T-Cell Therapies vs Bispecific Antibodies in R/R Multiple Myeloma

Amandeep Godara, MBBS, a medical oncologist, the Huntsman Cancer Institute, assistant professor, the Division of Hematology and Hematologic Malignancies, the University of Utah, discusses CAR T-cell therapies currently available for patients with multiple myeloma.

There are currently 2 CAR T-cell therapies that are FDA approved for the treatment of patients with multiple myeloma, including idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti), Godara explains. 

 in February 2022, both for patients with relapsed/refractory multiple myeloma. Both CAR T-cell therapies are indicated for patients who have received 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD 38 antibody. Ide-cel and cilta-cel were approved based on the results of the phase 2 KarMMA trial (NCT03361748) and the phase 1b/2 CARTITUDE-1 trial (NCT03548207), respectively, Godara adds.

When looking at the patient populations included in these clinical trials, patients enrolled were generally younger than the average patient with multiple myeloma, Godara explains. Patients also received a median of 5 to 6 prior lines of therapy during these trials, Godara notes.

Looking to real-world data for patients with multiple myeloma, findings presented at the 2022 ASH Annual Meeting showed that these patients are older than those enrolled on these clinical trials, and they are more likely to have other comorbidities, such as chronic kidney disease. These characteristics may have otherwise made these real-world patients ineligible for enrollment on these clinical trials that led to the approval of ide-cel and cilta-cel, Godara notes. However, there are real-world data indicating that CAR T-cell therapy can be safely used in patients who may be older or have additional comorbidities, and these CAR T-cell therapies have become options for these patients, Godara concludes.

Amandeep Godara, MBBS, discusses CAR T-cell therapies currently available for patients with multiple myeloma.

Dr. Godara on Approved CAR T-cell Therapies in Multiple Myeloma

Amandeep Godara, MBBS, a medical oncologist, the Huntsman Cancer Institute, assistant professor, the Division of Hematology and Hematologic Malignancies, the University of Utah, discusses the current treatment strategies following first relapse for patients with multiple myeloma.

When a patient with multiple myeloma experiences their first disease relapse, it is important to determine if the relapse occurred while a patient was on treatment with lenalidomide (Revlimid) or if relapse took place when the patient was off lenalidomide, Godara begins. Lenalidomide is used in the maintenance setting for patients who have undergone autologous stem cell transplant (ASCT), as well as those who are not eligible for transplant, Godara expands. Whether a patient is sensitive or refractory to lenalidomide will help inform the next choice of treatment, Godara adds.

For patients who are sensitive to lenalidomide and have not been exposed or are not refractory to an anti-CD38 antibody, subsequent treatment can consist of a combination of daratumumab (Darzalex), lenalidomide, and dexamethasone, Godara continues. However, for patients who are sensitive to lenalidomide but are refractory to an anti-CD38 antibody, lenalidomide could be combined with another proteasome inhibitor, such as carfilzomib (Kyprolis).

For patients who progress and are refractory to lenalidomide, the combination of daratumumab with another type of proteasome inhibitor, such as carfilzomib, could be an option. Godara notes. Notably,

bortezomib (Velcade) could be combined with an anti-CD38 antibody for these patients, only if they patient are not yet refractory to bortezomib, Godara adds.

Given the number of combination therapies available in the relapse setting, it is important to understand these factors when selecting subsequent therapy after first relapse, Godara concludes.

Amandeep Godara, MBBS, discusses the current treatment strategies following first relapse for patients with multiple myeloma.

Amandeep Godara, MBBS

Articles

Dr Godara on the Selection of CAR T-Cell Therapies vs Bispecific Antibodies in R/R Multiple Myeloma

Dr. Godara on Approved CAR T-cell Therapies in Multiple Myeloma

Dr. Godara on Treatment Strategies Following First Relapse in Multiple Myeloma