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CAR T-Cell Therapy: Promising Treatments in Development for DLBCL
There have been several recent developments in the treatment of B-cell lymphoma; however, one of the most significant advances has been the development of chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a type of personalized immunotherapy that can help cure some people with aggressive non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), the most common form of aggressive NHL. CAR T-cell therapy has revolutionized the treatment of hematologic malignancies over the past 5 years, with impressive response rates and durable remissions for patients who previously had no viable options. This strategy is highly effective in patients with relapsed/refractory DLBCL, as well as mantle cell lymphoma, follicular lymphoma, acute lymphoblastic leukemia (ALL), and multiple myeloma, as evidenced by recent regulatory approvals.
In 2021, the FDA also approved lisocabtagene maraleucel (liso-cel), a new CAR T-cell therapy for the treatment of adults with relapsed or refractory (nonresponsive) large B-cell lymphoma (LBCL) have been treated with at least 2 prior lines of therapy. These products have design differences, including differences in the costimulatory domain, mechanism of gene/transgene delivery, ability for cryopreservation, and need for T-cell selection.
The CAR T-cell therapy axi-cel demonstrated superior results in the ZUMA-7 clinical trial, which compared CAR T-cell therapy directly to traditional chemotherapy with intended autologous stem cell transplant (ASCT). About 55% of patients were still alive 4 years after receiving axi-cel, compared with 46% of those who initially received the standard treatment for relapsed disease. Based on these results, axi-cel is now the preferred treatment for people whose DLBCL has recurred with 12 months of front-line treatment or who are resistant to standard initial treatment.
Additionally, the BELINDA trial was a randomized phase 3 trial that compared CAR T-cell therapy with liso-cel with second-line chemotherapy with planned ASCT. Like ZUMA-7, this study also demonstrated an improvement in progression-free survival (PFS) compared to standard treatment. As such, CAR T-cell therapy represents the new standard of care for second-line treatment in appropriate patients with refractory or early relapsing LBCL.
There have been several other recent studies on the use of CAR T-cell therapy for B-cell lymphoma. One study, published in Blood Advances (2023), found that receiving a greater number of therapies prior to CAR T-cell therapy is associated with poorer outcomes in patients with aggressive relapsed/refractory B-cell NHL. The study, which included 514 patients from 13 centers treated with CAR-T for aggressive B-cell NHL between 2015 and 2021, found that a greater number of lines of therapy before CAR-T apheresis and bridging therapy were predictive of inferior PFS and overall survival.
Another study compared 2 CD19-targeting CAR T-cell treatments, axi-cel and tisa-cel, with ASCT in the second line setting for LBCL. The study found that axi-cel was superior to ASCT, with longer median event-free survival and a higher response rate. However, tisa-cel was not found to be superior to ASCT. Further studies will be needed to definitively characterize the relative benefits of CAR-T cell therapies and standard second-line treatments for different subgroups of patients with LBCL.
An increasing number of effective targeted agents for DLBCL, including novel monoclonal antibodies (tafasitamab) and antibody-drug conjugates (polatuzumab vedotin and loncastuximab teserine), are being used in earlier lines of therapy. Additionally, 2 anti-CD20 bispecific antibodies (epcoritamab and glofitamab) have gained approval for relapsed/refractory DLBCL due to high response rates. Future studies will be needed to determine if treatment with these agents can produce durable remissions like that of CAR-T cell therapy.
There have been several recent developments in the treatment of B-cell lymphoma; however, one of the most significant advances has been the development of chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a type of personalized immunotherapy that can help cure some people with aggressive non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), the most common form of aggressive NHL. CAR T-cell therapy has revolutionized the treatment of hematologic malignancies over the past 5 years, with impressive response rates and durable remissions for patients who previously had no viable options. This strategy is highly effective in patients with relapsed/refractory DLBCL, as well as mantle cell lymphoma, follicular lymphoma, acute lymphoblastic leukemia (ALL), and multiple myeloma, as evidenced by recent regulatory approvals.
In 2021, the FDA also approved lisocabtagene maraleucel (liso-cel), a new CAR T-cell therapy for the treatment of adults with relapsed or refractory (nonresponsive) large B-cell lymphoma (LBCL) have been treated with at least 2 prior lines of therapy. These products have design differences, including differences in the costimulatory domain, mechanism of gene/transgene delivery, ability for cryopreservation, and need for T-cell selection.
The CAR T-cell therapy axi-cel demonstrated superior results in the ZUMA-7 clinical trial, which compared CAR T-cell therapy directly to traditional chemotherapy with intended autologous stem cell transplant (ASCT). About 55% of patients were still alive 4 years after receiving axi-cel, compared with 46% of those who initially received the standard treatment for relapsed disease. Based on these results, axi-cel is now the preferred treatment for people whose DLBCL has recurred with 12 months of front-line treatment or who are resistant to standard initial treatment.
Additionally, the BELINDA trial was a randomized phase 3 trial that compared CAR T-cell therapy with liso-cel with second-line chemotherapy with planned ASCT. Like ZUMA-7, this study also demonstrated an improvement in progression-free survival (PFS) compared to standard treatment. As such, CAR T-cell therapy represents the new standard of care for second-line treatment in appropriate patients with refractory or early relapsing LBCL.
There have been several other recent studies on the use of CAR T-cell therapy for B-cell lymphoma. One study, published in Blood Advances (2023), found that receiving a greater number of therapies prior to CAR T-cell therapy is associated with poorer outcomes in patients with aggressive relapsed/refractory B-cell NHL. The study, which included 514 patients from 13 centers treated with CAR-T for aggressive B-cell NHL between 2015 and 2021, found that a greater number of lines of therapy before CAR-T apheresis and bridging therapy were predictive of inferior PFS and overall survival.
Another study compared 2 CD19-targeting CAR T-cell treatments, axi-cel and tisa-cel, with ASCT in the second line setting for LBCL. The study found that axi-cel was superior to ASCT, with longer median event-free survival and a higher response rate. However, tisa-cel was not found to be superior to ASCT. Further studies will be needed to definitively characterize the relative benefits of CAR-T cell therapies and standard second-line treatments for different subgroups of patients with LBCL.
An increasing number of effective targeted agents for DLBCL, including novel monoclonal antibodies (tafasitamab) and antibody-drug conjugates (polatuzumab vedotin and loncastuximab teserine), are being used in earlier lines of therapy. Additionally, 2 anti-CD20 bispecific antibodies (epcoritamab and glofitamab) have gained approval for relapsed/refractory DLBCL due to high response rates. Future studies will be needed to determine if treatment with these agents can produce durable remissions like that of CAR-T cell therapy.
There have been several recent developments in the treatment of B-cell lymphoma; however, one of the most significant advances has been the development of chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a type of personalized immunotherapy that can help cure some people with aggressive non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), the most common form of aggressive NHL. CAR T-cell therapy has revolutionized the treatment of hematologic malignancies over the past 5 years, with impressive response rates and durable remissions for patients who previously had no viable options. This strategy is highly effective in patients with relapsed/refractory DLBCL, as well as mantle cell lymphoma, follicular lymphoma, acute lymphoblastic leukemia (ALL), and multiple myeloma, as evidenced by recent regulatory approvals.
In 2021, the FDA also approved lisocabtagene maraleucel (liso-cel), a new CAR T-cell therapy for the treatment of adults with relapsed or refractory (nonresponsive) large B-cell lymphoma (LBCL) have been treated with at least 2 prior lines of therapy. These products have design differences, including differences in the costimulatory domain, mechanism of gene/transgene delivery, ability for cryopreservation, and need for T-cell selection.
The CAR T-cell therapy axi-cel demonstrated superior results in the ZUMA-7 clinical trial, which compared CAR T-cell therapy directly to traditional chemotherapy with intended autologous stem cell transplant (ASCT). About 55% of patients were still alive 4 years after receiving axi-cel, compared with 46% of those who initially received the standard treatment for relapsed disease. Based on these results, axi-cel is now the preferred treatment for people whose DLBCL has recurred with 12 months of front-line treatment or who are resistant to standard initial treatment.
Additionally, the BELINDA trial was a randomized phase 3 trial that compared CAR T-cell therapy with liso-cel with second-line chemotherapy with planned ASCT. Like ZUMA-7, this study also demonstrated an improvement in progression-free survival (PFS) compared to standard treatment. As such, CAR T-cell therapy represents the new standard of care for second-line treatment in appropriate patients with refractory or early relapsing LBCL.
There have been several other recent studies on the use of CAR T-cell therapy for B-cell lymphoma. One study, published in Blood Advances (2023), found that receiving a greater number of therapies prior to CAR T-cell therapy is associated with poorer outcomes in patients with aggressive relapsed/refractory B-cell NHL. The study, which included 514 patients from 13 centers treated with CAR-T for aggressive B-cell NHL between 2015 and 2021, found that a greater number of lines of therapy before CAR-T apheresis and bridging therapy were predictive of inferior PFS and overall survival.
Another study compared 2 CD19-targeting CAR T-cell treatments, axi-cel and tisa-cel, with ASCT in the second line setting for LBCL. The study found that axi-cel was superior to ASCT, with longer median event-free survival and a higher response rate. However, tisa-cel was not found to be superior to ASCT. Further studies will be needed to definitively characterize the relative benefits of CAR-T cell therapies and standard second-line treatments for different subgroups of patients with LBCL.
An increasing number of effective targeted agents for DLBCL, including novel monoclonal antibodies (tafasitamab) and antibody-drug conjugates (polatuzumab vedotin and loncastuximab teserine), are being used in earlier lines of therapy. Additionally, 2 anti-CD20 bispecific antibodies (epcoritamab and glofitamab) have gained approval for relapsed/refractory DLBCL due to high response rates. Future studies will be needed to determine if treatment with these agents can produce durable remissions like that of CAR-T cell therapy.