Jeffery Zonder, MD, is the leader of the Multiple Myeloma Sub-Committee at Barbara Ann Karmanos Cancer Institute and a professor of medicine in the Department of Hematology and Oncology at Wayne State University School of Medicine.

Jeffery Zonder, MD, leader, the Multiple Myeloma Sub-committee, the Barbara Ann Karmanos Cancer Institute, professor of medicine, the Departments of Hematology and Oncology, Wayne State University School of Medicine, discusses the process of choosing between CAR T-cell therapy and bispecific antibody approaches for the treatment of patients with relapsed/refractory multiple myeloma.

Two CAR T-cell therapies are currently approved by the FDA for patients with multiple myeloma: 

ciltacabtagene autoleucel (cilta-cel; Carvykti)

, which was approved in February 2022. Additionally, in October 2022, 

the regulatory agency granted accelerated approval to the bispecific antibody teclistamab-cqyv (Tecvayli)

 for adult patients with relapsed or refractory multiple myeloma. All 3 treatments are indicated for patients who have received at least 4 prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Notably, both ide-cel and cilta-cel are BCMA-targeted CAR T-cell therapies, and teclistamab targets both BMCA and CD3.

Among BCMA-targeted therapies, CAR T-cell therapy has the advantage of being administered at as a single infusion, and both ide-cel and cilta-cel have been associated with high response rates, Zonder begins. However, access to CAR T-cell therapy remains an obstacle for this patient population, Zonder says, adding that their is a waiting period for treatment slots at most cancer centers that can administer CAR T-cell therapy. Additionally, after T cells are collected and sent for manufacturing, there is another waiting period prior to their administration, Zonder continues. These time constraints may make CAR T-cell therapy unfeasible for some patients who fall under the approved indication, since a patient who has rapidly progressing disease after 4 prior lines of therapy may not be able to wait for CAR T-cell therapy, Zonder says. Oftentimes, bridging therapy will be needed keep the disease at bay during the waiting process.

Although teclistamab, in particular, is administered weekly, bispecific antibodies are an off-the-shelf therapy, so the treatment process can be started right away. Although response rates are not as high for bispecific antibodies compared with CAR T-cell therapy, these agents represent a significant leap forward compared to previous treatment options in this setting, Zonder says. Choosing between CAR T-cell therapy and a bispecific antibody comes down to how urgently the therapy is needed for a patient, Zonder concludes.

Videos

Jeffery Zonder, MD, discusses the process of choosing between CAR T-cell therapy and bispecific antibody approaches for the treatment of patients with relapsed/refractory multiple myeloma.

Dr Zonder on CAR T-cell Therapy Vs Bispecific Antibodies in Relapsed/Refractory Myeloma 

Jeffrey Zonder, MD, professor of hematology-oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, discusses the ZUMA-2 trial in mantle cell lymphoma (MCL) and the ZUMA-5 trial in indolent non-Hodgkin lymphoma (iNHL).

The phase 2 ZUMA-2 trial evaluated brexucabtagene autoleucel (Tecartus) in patients with relapsed/refractory MCL who received up to 5 prior lines of therapy. Almost all patients had received prior anthracycline or bendamustine, and 100% of patients had received a prior anti-CD20 antibody and BTK inhibitor treatment with ibrutinib (Imbruvica) or acalabrutinib (Calquence).

The ​phase 2 ZUMA-5 trial evaluated axicabtagene ciloleucel (axi-cel; Yescarta) in patients with relapsed/refractory, low-grade, iNHL,including follicular lymphoma or marginal zone lymphoma, that has progressed after at least 2 lines of treatment, says Zonder. 

Although these studies used different CD19-directed CAR T-cell products, they both demonstrated high response rates in patients who had received multiple prior lines of therapy. Moreover, the majority of patients who achieved a complete response experienced durable response, Zonder concludes.

Jeffrey Zonder, MD, discusses the ZUMA-2 trial in mantle cell lymphoma and the ZUMA-5 trial in indolent non-Hodgkin lymphoma. 

Dr. Zonder on the ZUMA-2 and ZUMA-5 Trials in MCL and iNHL 

Jeffrey Zonder, MD, associate professor of oncology and medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, discusses induction therapy in the treatment of patients with newly diagnosed multiple myeloma.

Both carfilzomib (Kyprolis) and bortezomib (Velcade) can be used as part of a patient’s induction regimen, explains Zonder, but there is a split in opinion regarding early incorporation of carfilzomib into treatment. The ongoing phase III ENDURANCE trial will be an important aspect in answering this question. In the trial, patients will be randomized to receive lenalidomide (Revlimid) and dexamethasone with either bortezomib (VRD) or carfilzomib for 9 months, followed by lenalidomide maintenance therapy.

Zonder says that his default has traditionally been VRD, though some physicians will substitute carfilzomib in for patients with high-risk disease. Zonder adds that this is an option—it is not yet the default standard across the country.

Jeffrey Zonder, MD

Articles

Dr Zonder on CAR T-cell Therapy Vs Bispecific Antibodies in Relapsed/Refractory Myeloma

Dr. Zonder on the ZUMA-2 and ZUMA-5 Trials in MCL and iNHL

Dr. Zonder on Induction Therapy in Newly Diagnosed Multiple Myeloma