Dr Herrera on Nivolumab vs Brentuximab Vedotin Plus AVD in Hodgkin Lymphoma

Alex Herrera, MD, chief, Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, associate medical director, Briskin Center for Clinical Research, associate professor, Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, discusses safety and efficacy outcomes from the phase 3 SWOG S1826 trial (NCT03907488) of treatment with nivolumab (Opdivo) vs brentuximab vedotin (BV; Adcetris), both given with combination chemotherapy, in adolescent and adult patients with advanced classic Hodgkin lymphoma.

Notably, the investigation evaluated the 2 treatment options given with doxorubicin, vinblastine, and dacarbazine (AVD). The initial findings were reported with only 12.1 months of follow-up (range, 0-38.6), Herrera begins. The goal in treating patients with advanced-stage Hodgkin lymphoma is to cure the disease, and most recurrences typically occur within the first 2 years post-therapy, he reports. One goal of SWOG S1826 was to determine whether the benefit of nivolumab plus AVD (N+AVD) vs BV plus AVD (BV+AVD) would continue over time. Now, with 2.1 years of follow-up (range, 0-4.2), investigators saw that the progression-free survival (PFS) benefit of N+AVD over BV+AVD was sustained, Herrera shares. Specifically, the 2-year PFS rate with N+AVD reached 92% (95% CI, 89%-94%), compared with 83% (95% CI, 79%-86%) with BV+AVD, yielding a hazard ratio of 0.45 (95% CI, 0.30-0.65).

Moreover, the benefit with N+AVD was consistent across diverse patient subgroups enrolled in the study. These included adolescents, older adults, patients with high- or low-risk disease, and patients with either stage III or stage IV disease, he notes. Observing this uniform improvement across all patient categories further reinforces the reliability of N+AVD, according to Herrera.

Additionally, investigators reported final toxicity outcomes, Herrera continues. Once therapy was completed, a noticeable difference emerged between the 2 arms: 22.2% of patients in the BV+AVD arm discontinued treatment with BV due to adverse effects (AEs), whereas 9.4% of patients in the N+AVD arm discontinued treatment with nivolumab, he says. Furthermore, 26.7% of patients receiving BV required BV dose reductions.

Importantly, no new safety signals were observed since the initial analysis, and the AEs remained consistent with prior observations, Herrera emphasizes. The use of radiation therapy remained minimal; 0.6% of patients in the N+AVD arm received radiation, underscoring the effectiveness of N+AVD, he concludes.

Videos

Alex Herrera, MD, discusses safety and efficacy outcomes with nivolumab plus AVD vs brentuximab vedotin plus AVD in advanced classic Hodgkin lymphoma.

, hosted by Matthew Lunning, DO, FACP, is a podcast that seeks to translate the latest hematologic oncology research findings into practical clinical implications for the treatment of patients with hematologic malignancies. Dr Lunning is an associate professor in the Division of Oncology & Hematology, associate vice chair of research in the Department of Internal Medicine, and assistant vice chancellor of clinical research at the University of Nebraska Medical Center in Omaha.

In this episode, Dr Lunning sat down with Alex Herrera, MD, to discuss the frontline management of Hodgkin lymphoma. Dr Herrera is an associate professor in and chief of the Division of Lymphoma in the Department of Hematology & Hematopoietic Cell Transplantation, as well as the associate medical director of the Briskin Center for Clinical Research at City of Hope in Duarte, California. 

Drs Lunning and Brander highlighted the rationale for and potential implications of the phase 3 SWOG 1826 trial (NCT03907488) of nivolumab (Opdivo) or brentuximab vedotin (Adcetris) plus combination chemotherapy in patients with newly diagnosed classic Hodgkin lymphoma, the collaborative efforts between pediatric and adult oncologists that led to the successful initiation of this trial, potential future directions for this research, and more.

Podcasts

Dr Lunning sits down with Alex Herrera, MD, to discuss the frontline management of Hodgkin lymphoma, including the SWOG 1826 trial.

Lunning and Herrera Highlight Frontline Hodgkin Lymphoma Management Strategies

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OncLive® will be LIVE with OncLive® News Network: On Location at the 2023 ASCO Annual Meeting. Each day, we will broadcast a series of interviews with top thought leaders, to learn their thoughts and reactions to data presented across hematologic oncology during the conference.

Gaining Ground in Gynecologic and Hematologic Cancers at ASCO 2023: Drs Herrera, Westin, and Jabbour

Alex Herrera, MD, a hematologist/oncologist, and an assistant professor in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, discusses the potential for CAR T-cell therapy in earlier lines of treatment for patients with diffuse large B-cell lymphoma (DLBCL).

Several ongoing trials are examining whether autologous CD19-directed CAR T cells can be utilized earlier than standard salvage chemotherapy or autologous stem cell transplant, which are often used to treat patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma, according to Herrera. If these ongoing trials, such as the phase 3 ZUMA-7 trial (NCT03391466) examining axicabtagene ciloleucel (axi-cel; Yescarta) vs standard of care as second-line therapy in patients with relapsed/refractory DLBCL, show positive results, CAR T-cell therapy may become the standard second-line treatment for this patient population, Herrera says.

Additionally, the phase 2 ZUMA-12 trial (NCT03761056), which is evaluating CAR T cells in patients receiving frontline therapy who have a positron emission tomography scan that is positive after 2 cycles of systemic chemotherapy, has shown promising results, Herrera adds. CAR T-cell therapy will continue to be evaluated in high-risk groups of patients who are progressing, or who show signs of early progression with their frontline therapy, Herrera concludes.

Alex Herrera, MD, discusses the potential for CAR T-cell therapy in earlier lines of treatment for patients with diffuse large B-cell lymphoma.

Dr. Herrera on the Potential for Frontline CAR T-Cell Therapy in DLBCL

Alex Herrera, MD, a hematologist/oncologist, and an assistant professor in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, discusses the utility of CAR T cells in patients with hematologic cancers.

Thus far, autologous CAR T cells have demonstrated that robust antitumor, as well as durable responses in a sizable minority of patients, can be generated with a cellular therapy, according to Herrera. Additionally, there has been an increase in allogeneic, or off-the-shelf CAR T cells, being studied in clinical trials to examine how they compare with CD19-directed treatments, Herrera says.

Looking forward, there is still more to be learned about the durability of CAR T-cell therapy in patients, and how that correlates with the robustness of the antitumor response, Herrera continues. Allogeneic CAR T cells represent a potential option for patients who are unable to wait for the production of autologous CAR T cells; however, more efforts are underway to further optimize this treatment, Herrera concludes.

Alex Herrera, MD, discusses the utility of CAR T cells in patients with hematologic cancers.

Dr. Herrera on the Utility of CAR T-Cell Therapy in Hematologic Cancers

Alex Herrera, MD, a hematologist/oncologist, and an assistant professor in the Department of Hematology and Hemtopoietic Cell Transplantation at City of Hope, discusses the potential role of camidanlumab tesirine (ADCT-301) in patients with relapsed/refractory Hodgkin Lymphoma, which is currently being examined in a phase 2 clinical trial (NCT04052997).

Patients with relapsed/refractory Hodgkin lymphoma who have developed resistance to brentuximab vedotin (Adcetris) and/or PD-1 blockade have limited treatment options, according to Herrera. The curative potential of these agents, especially when administered once a patient is relapsed/refractory or given a monotherapy, is fairly low, Herrera says. Due to this, there is an urgent need for novel agents utilizing new targets that can demonstrate efficacy in patients who have resistant disease.

Camidanlumab tesirine can potentially address the challenge faced in this patient population, Herrera says. The phase 2 trial enrolled patients who had previously been treated with brentuximab vedotin; therefore, camidanlumab tesirine can be applied to this patient population, Herrera says. The safety and efficacy data from the trial will help determine the role of the agent in patients with relapsed/refractory Hodgkin lymphoma, Herrera concludes.

Alex Herrera, MD, discusses the potential role of camidanlumab tesirine in patients with relapsed/refractory Hodgkin Lymphoma, which is currently being examined in a phase 2 clinical trial.

Dr. Herrera on Camidanlumab Tesirine in Relapsed/Refractory Hodgkin Lymphoma

Alex Herrera, MD, assistant professor, Department of Hematology and Hematologic Cell Transplantation, City of Hope, discusses polatuzumab vedotin in diffuse large B-cell lymphoma (DLBCL).

In phase I studies, single-agent polatuzumab vedotin has proved to be safe to use in this patient population. Investigators wanted to build upon this potential by studying this agent in combination trials.

The addition of polatuzumab vedotin to bendamustine and rituximab (Rituxan) was shown to be tolerable in a phase I study. A phase II randomized study was then conducted and with the addition of polatuzumab vedotin to bendamustine and rituxmab, more patients were able to complete the 6-week cycle than those who did not receive polatuzumab vedotin.

Herrera says that these studies suggest this is an active triplet that is worth studying in this population.

Alex Herrera, MD, assistant professor, Department of Hematology and Hematologic Cell Transplantation, City of Hope, discusses polatuzumab vedotin in diffuse large B-cell lymphoma.

Dr. Herrera Discusses Polatuzumab Vedotin in DLBCL

Alex Herrera, MD, assistant professor, Department of Hematology and Hematologic Cell Transplantation, City of Hope, discusses next steps for a phase I/II study of brentuximab vedotin (Adcetris) in combination with nivolumab (Opdivo) in patients with relapsed or refractory Hodgkin lymphoma.

 The next steps concerning this study are to combine the drugs, brentuximab vedotin and nivolumab,  on the first day of treatment to see if it changes the rate of infusion reactions. All of the infusion reactions were mild and manageable and any interruptions of the drug were not permanent, Herrera explains.

 The goal is to enroll more patients to gather additional information about the effectiveness of these drugs, but also to limit infusion-related reactions by changing how the drugs are given, Herrera says.

Alex Herrera, MD

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