by Dr. C.H. Weaver M.D. 6/2023
The cancer immunotherapy strategy known as programmed cell death 1 (PD-1) has generated great excitement for its ability to help the immune system recognize and attack lung, melanoma and other cancers. According to study results released at the 2023 ASCO Annual Meeting Opdivo may be a new standard of care for the initial treatment of Hodgkin lymphoma (HL).
Hodgkin’s lymphoma is a cancer of the lymph system. It typically begins in the lymph nodes in one region of the body and then spreads throughout the lymph system. Hodgkin’s lymphoma is one of the more curable cancers with effective treatments available at several stages of disease. First-line treatment of HL was with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy for many years. The U.S. Food and Drug Administration (FDA) approved Adcetris (brentuximab vedotin) in combination with AVD (Adriamycin, vinblastine and dacarbazine) chemotherapy to replace ABVD because Adcetris reduced the risk of relapse, improve survival and avoided lung toxicity from the drug bleomycin.
Opdivo (Nivolumab) belongs to a class of medicines called PD-1 inhibitors that help the immune system recognize and attack cancer. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 may enhance the ability of the immune system to fight cancer. Opdivo works by blocking PD-1. This treatment strategy has previously produced impressive results in melanoma and other cancer types.1-3 The US FDA granted Opdivo breakthrough therapy designation and ultimately full FDA approval for treatment of advanced HL.5
Opdivo in combination with AVD has now been compared to Adcetris plus AVD and is reported to delay cancer progression when directly compared with Adcetris in patients with advanced-stage classical Hodgkin lymphoma according to findings from a clinical trial presented during the 2023 ASCO Annual Meeting. With a median follow-up of 12 months, 94% of patients in the clinical trial treated with Opdivo plus AVD survived without lymphoma progression compared with 86% of patients treated with Adcetris plus AVD.7
The most common side effects with Opdivo plus AVD included neutropenia, anemia, and sensory neuropathy and the rates of their occurrence were similar to Adcetris plus AVD. Opdivo plus AVD should now be considered a standard treatment option for newly diagnosed HL.
Opdivo Immunotherapy Effective “Bridge” to ASCT
In a large proportion of patients with relapsed or refractory Hodgkin lymphoma (HL), the use of Opdivo immunotherapy is an effective “bridge therapy” to autologous stem cell transplantation (ASCT), according to interim results from a phase II trial presented at the 2019 ASH Annual Meeting.
Doctors routinely use chemotherapy to control HL while preparing for ASCT. Chemotherapy is associated with significant side effects and additional damage to the blood producing stem cells in the bone marrow required for ASCT. An immunotherapy approach could help to reduce side effects and not be detrimental to blood stem cell collection.
Researchers evaluated a positron emission tomography (PET)-adapted treatment strategy. Patients with relapsed or refractory HL received salvage therapy with Opdivo every two weeks for up to six cycles. Participants underwent PET-computed tomography (PET-CT) at cycle 3 and cycle 6. If patients were in complete remission (CR) at cycle 6, they proceeded to ASCT; if patients had not achieved a remission, they received Opdivo plus ICE chemotherapy (ifosfamide, carboplatin, and etoposide; NICE) for two additional cycles.
At the end of cycle 3, the overall response to Opdivo was 89% with 60% of patients attaining a complete disappearance of their cancer. After cycle 6 of Opdivo rate the complete remission rate increased to 77%. The patients who had either stable or progressive disease per PET-CT during and after salvage Opdivo responded to treatment with NICE.
Twenty-seven participants who completed six cycles of Opdivo proceeded to ASCT directly after salvage therapy. At one year 74% of these patients survived without cancer progression and 97% survived overall.
According to the researchers the side effects of this approach was minimal and the patients proceeding to ASCT were in better shape overall than would be expected historically. Opdivo “bridging therapy” to ASCT appears effective, is associated with fewer side effects than chemotherapy and unlike chemotherapy can be administered on an outpatient bases at lower costs. Longer follow up of patients treated with Opdivo and ASCT is required to better understand effectiveness and whether the combined approach is associated with immune or other side effects.6
References:
- Robert C, Long GV, Brady B, et al. Nivolumab in Previously Untreated Melanoma without BRAF Mutation. New England Journal of Medicine [early online publication]. November 16, 2014.
- Topalian SL, Sznol M, McDermott DF, et al. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal of Clinical Oncology [early online publication]. March 3, 2014. doi: 10.1200/JCO.2013.53.0105.
- Study Comparing Opdivo (nivolumab) to Chemotherapy in Treatment Naïve Advanced Melanoma Patients Marks First PD-1 Immune Checkpoint Inhibitor to Demonstrate a Survival Benefit in a Phase 3 Trial [press release]. Bristol-Myers Squibb website. Available here.
- Ansell S, Lesokhin A, Borrello I, et al. PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin’s Lymphoma. The New England Journal of Medicine. December 6, 2014DOI: 10.1056/NEJMoa1411087
- Nivolumab (Opdivo) for Hodgkin Lymphoma
- Herrera AF, Chen RW, Palmer J, et al. PET-adapted nivolumab or nivolumab plus ICE as first salvage therapy in relapsed or refractory Hodgkin lymphoma. Abstract #239. Presented at the 2019 ASH Annual Meeting, December 7, 2019; Orlando, FL.
- Herrera AF, LeBlanc ML, Castellino SM, et al. SWOG S1826, a randomized study of nivolumab(N)-AVD versus brentuximab vedotin(BV)-AVD in advanced stage (AS) classic Hodgkin lymphoma (HL). J Clin Oncol. 2023;41(suppl 17):LBA4. doi:10.1200/JCO.2023.41.16_suppl.LBA4
