Georgina V. Long, MD, PhD, on Resected Melanoma: Biomarkers for and Efficacy of Adjuvant Nivolumab vs Placebo
2023 ASCO Annual Meeting
Georgina V. Long, MD, PhD, of Melanoma Institute Australia and The University of Sydney, discusses new data showing that patients with resected stage IIB/C melanoma who were treated with adjuvant nivolumab had prolonged recurrence-free survival compared with placebo across all biomarker subgroups. The baseline biomarkers most predictive of prolonged recurrence-free survival with nivolumab were high interferon gamma score, high tumor mutational burden, CD8 T-cell infiltration, and low C-reactive protein (Abstract 9504).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Georgina V. Long:
Resected Stage 2B and 2C melanoma has a very poor prognosis. In fact, at five years, patients with stage 2C melanoma have a 45% risk of recurrence. And for stage 2B melanoma, 35% risk of recurrence. The survival of this group of patients is worse than that of stage 3A melanoma and the survival of stage 2C melanoma is equivalent to the survival of stage 3B melanoma. This is a poor prognostic group. Checkmate 76K explored adjuvant nivolumab versus placebo in resected stage 2B and 2C melanoma in patients who had undergone a wide local excision and a sentinel node biopsy, which was negative.
790 patients were randomized two to one to nivolumab versus placebo. We've already seen the relapse-free survival primary analysis last year, and there was a 58% reduction in the risk of recurrence with adjuvant nivolumab. We are now presenting the exploratory biomarker analysis from this trial. So baseline, primary melanoma tissue, and baseline CRP, serum CRP was correlated with outcome within each arm and versus each arm. And what we found was that for every biomarker subgroup, nivolumab improved the relapse-free survival over placebo.
And this included tumor mutation burden, interferon gamma, PD-L1 expression at baseline, CD8 infiltration at baseline, the CRP. So when we compared the prognostic biomarkers overall in the trial, we found that the two factors that were most important for prognosis, so predicting recurrence in the total trial population, that was the CRP and the stage. However, when we did our multivariate model to look at what was predictive of best outcome with adjuvant nivolumab over placebo, we found that the baseline biomarkers that were predictive or most predictive were the interferon gamma at baseline and the tumor mutation burden.
Our next steps are to make a multifactorial model, which includes both clinical and tissue biomarkers to predict outcome of patients with resected 2B and 2C melanoma treated with adjuvant nivolumab.
Jennifer L. Crombie, MD, of Dana-Farber Cancer Institute, discusses the historically poor outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Her study examined real-world data on the use of novel therapies in this population and found that outcomes with second- and third-line regimens of polatuzumab vedotin-piiq plus bendamustine and rituximab and tafasitamab plus lenalidomide remain suboptimal, with worse outcomes particularly after chimeric antigen receptor T-cell therapy (Abstract 7552).
Amer Methqal Zeidan, MBBS, MHS, of Yale University and Yale Cancer Center, discusses phase III findings on the first-in-class telomerase inhibitor imetelstat, which was given to patients with heavily transfusion-dependent non-del(5q) lower-risk myelodysplastic syndromes that are resistant to erythropoiesis-stimulating agents. Imetelstat resulted in a significant and sustained red blood cell (RBC) transfusion independence in 40% of these heavily transfused patients. The response was also durable and accompanied by an impressive median hemoglobin rise of 3.6 g/dL, and seen in patients with and without ring sideroblasts. Importantly, reduced variant allele frequency was observed in the most commonly mutated myeloid genes which correlated with duration of transfusion independence and hemoglobin rise, therefore suggesting a disease-modifying potential of this agent (Abstract 7004).
Aaron T. Gerds, MD, of Cleveland Clinic Taussig Cancer Institute, talks about treating the anemia many patients with myelofibrosis experience because of JAK inhibitor therapy. The ACE-536-MF-001 study showed that luspatercept improved anemia and transfusion burden in this population, with a safety profile consistent with that in previous studies (Abstract 7016).
Jason J. Luke, MD, of the University of Pittsburgh Medical Center Hillman Cancer Center, discusses adjuvant pembrolizumab, which, in previous results, improved distant metastasis– and recurrence-free survival in patients with resected stage IIB or IIC melanoma vs placebo. After a median follow-up of 39.4 months, adjuvant pembrolizumab continued to show a benefit over placebo, with no new safety signals (Abstract LBA9505).
Bobbie J. Rimel, MD, of Cedars-Sinai Medical Center, and Kathleen N. Moore, MD, of the Stephenson Oklahoma Cancer Center at the University of Oklahoma, discuss phase III results from the MIRASOL trial, which showed that mirvetuximab soravtansine-gynx prolonged overall survival vs investigator’s choice chemotherapy in patients with platinum-resistant ovarian cancer with high folate receptor-alpha expression. The findings suggest a new standard of care for this disease (Abstract LBA5507).