Melanoma, Pediatric Oncology, Lymphoma & Plasma Cell Disorders Dominate Research Presentations from NYU Langone Medical Center at ASCO’s 2015 Conference
Epidemiology Studies Also Play a Prominent Role
NYU Langone Medical Center and its Laura and Isaac Perlmutter Cancer Center will have a high profile at the 51st Annual Meeting of the American Society for Clinical Oncology (ASCO), with researchers presenting close to 30 abstracts accepted for oral, poster, and publication presentations.
Leading the way are eight oral abstract and poster presentations on melanoma for which an NYU Langone researcher is either a senior, lead, or contributing author. While many of these studies are multi-institutional, five poster presentations are led by the Perlmutter Cancer Center’s Interdisciplinary Melanoma Cooperative Group. These include:
- Immunologic profile of melanoma brain metastases (MBM) in patients (pts) with prolonged survival
Conclusions: The data demonstrate that radiation therapy can induce lymphocyte activation, but also signals that suppress the immune system. Interestingly, patients with brain metastases who live lionger have an enhanced activation signature. Indentifying patients with this enhanced immune signature could aid in prognostication and prediction of response to immunotherapy.
- The expression quantitative trait loci (eQTLs) and their association with melanoma clinical outcomes
Conclusions: This study identifies several genetic markers that likely affect that immune response to melanoma and which are powerful predictors of melanoma prognosis. The findings indicate that not only mutations within the tumor, but also the patient’s genetic background, can affect prognosis in this disease.
- The effect of ipilimumab on natural killer cells identifies the subset of advanced melanoma patients with clinical response
Conclusions: CTLA-4 is expressed mainly on T cells, including regulatory T cells, with no expression on natural killer cells. Nevertheless, we have shown an effect of IPI on the phenotype of NK cells, with an increase of IL-2R expression. More importantly, the effect of IPI on NK cells (better response to IL-2 stimulation and cytotoxicity) is associated with a good clinical response. The mechanism behind this effect is not clear yet, however this may be indirect through the action of IPI on other immune cells.
- De novo versus nevus-associated melanomas: Differences in associations with prognostic indicators and survival
Conclusions: These data suggest that melanomas that appear to arise spontaneously might be more aggressive than those that are associated with prior moles, and might also differ in their molecular pathogenesis. These findings may also have implications for early detection programs.
- Extended follow-up results of phase Ib study (BRIM7) of vemurafenib (VEM) with cobimetinib (COBI) in BRAF-mutant melanoma
Conclusions: Vemurafenib and Cobimetinib continue to show robust efficacy in BRAF inhibitor-naive patients, with a manageable and tolerable safety profile without new safety signals. Median overall survival in BRAF inhibitor-naive patients was greater than two years. Late complete response conversions indicate persistent activity with continued therapy.
Spearheading NYU Langone’s presentations of melanoma clinical trials presented at ASCO 2015 are:
- Anna C. Pavlick, DO, Associate Professor, Department of Medicine, Division of Medical Oncology, and the Ronald O. Perelman Department of Dermatology, and Medical Director of the Clinical Trials Office at the Perlmutter Cancer Center;
- Iman Osman, MD, Associate Professor, Departments of Dermatology, Urology and Medicine, and Associate Director of the Perlmutter Cancer Center and Director of its Interdisciplinary Melanoma Cooperative Group (IMCG);
- David Polsky, MD, PhD, The Alfred W. Kopf, MD Professor of Dermatologic Oncology and the Director of the Pigmented lesion Service, Ronald O. Perelman Department of Dermatology, Professor in the Department of Pathology, and a member of the IMCG; and
- Tomas Kirchhoff, PhD, Assistant Professor, Department of Population Health, Division of Epidemiology, and a member of the IMCG.
NYU Langone also will be part of several oral abstract and poster presentations by the Children’s Oncology Group on the topics of B-lymphoblastic leukemia and acute lymphoblastic leukemia. William L. Carroll, MD, the Julie and Edward J. Minskoff Professor of Pediatrics and Director of the Stephen D. Hassenfeld Children’s Center for Cancer and Blood Disorders at NYU Langone, will be presenting as part of an education session entitled Real-Time Molecular Genetic Profiling: The Future is Now (Or is It?). Dr. Carroll will present a study entitled State-of-the-Art Discovery with Tumor Profiling in Pediatric Oncology.
In addition, Dr. Carroll is represented as a co-investigator in the following presentations:
- Outcomes of dasatinib plus intensive chemotherapy or stem cell transplant (SCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) on Children’s Oncology Group AALL0622
Conclusions: Combining the targeted therapy dasatinib with intensive chemotherapy was well tolerated. Subjects with rapid response had excellent outcomes without the need for bone marrow transplant. Further follow-up and additional trials are necessary to define the relative role of dasatinib and another targeted agent, imatinib, in promoting long-term survival in pediatric Ph+ ALL.
- Neurocognitive function of children treated for high-risk B-acute lymphoblastic leukemia (HR-ALL) randomized to Capizzi (CMTX) versus high-dose methotrexate (HDMTX): A report from the Children’s Oncology Group (COG)
Conclusions: This study shows that even in the absence of cranial radiation, young survivors of high risk acute lymphoblastic leukemia are at risk for deficits in global intellectual functioning and processing speed. Critically, insurance status was also strongly associated with neurocognitive outcomes.
Lymphoma and plasma cell disorders are the focus of other sessions, at which NYU Langone and its Perlmutter Cancer Center will be well represented. Catherine S. Diefenbach, MD, Assistant Professor of Medicine, Division of Medical Oncology, will lead the following poster presentation:
- A phase I study with an expansion cohort of the combination of ipilimumab and brentuximab vedotin in patients with relapsed/refractory Hodgkin lymphoma: A trial of the ECOG-ACRIN Cancer Research Group (E4412)
Background: This phase I (or early phase study) aims to simulutaneously target both tumor cells and the “tumor-microenvironment” in patients with relapsed Hodgkin’s disease.
In addition, Dr. Diefenbach has contributed to other oral abstract and poster presentations, including:
- Two doses of polatuzumab vedotin (PoV, anti-CD79b antibody-drug conjugate) in patients (pts) with relapsed/refractory (RR) follicular lymphoma (FL): Durable responses at lower dose level
Conclusions: PoV+R in RR FL showed high ORR at both doses, with higher CR at 2.4 mg/kg. AEs and d/c rates were reduced at both doses if only the first 8 cycles are considered vs. those reported through study completion. The safety of PoV can be improved by shorter treatment and/or lower dose.
- Interim analysis of a phase I study of INCB040093, a PI3Kδ inhibitor, alone or in combination with INCB039110, a selective JAK1 inhibitor, in patients (pts) with relapsed or refractory (r/r) B-cell malignancies
Conclusions: These two early phase studies show that two “targeted therapies,” INCB0400093 and INCB039110 alone or in combination, could be tolerarted in heavily pre-treated patients with Hodgkin’s disease or other relapsed or refractory B cell lymphomas, and show promising efficacy. Larger studies are underway to evaluate their utility in greater detail.
Two NYU Langone-led epidemiologic studies, for which Stephanie V. Blank, MD, Associate Professor, Department of Obstetrics & Gynecology, serves as senior author, also will be presented at ASCO 2015:
- Is there a role for multi-gene screening panels in patients who previously underwent noninformative genetic testing?
Conclusions: This study indicates that the use of larger panels of “risk genes” can identify patients with genetic predispositon to cancer, who were not deemed “positive” using conventional genetic testing.
- The influence of BRCA variants of uncertain significance in cancer risk management decision-making
Conclusions: This study points to the need to individualize screening and prevention strategies for patients who undergo genetic testing and are found to have “variants” in the BRCA genes that whose causal significance is unknown. Such “variants of unknown significance” are likely to appear more and more frequently with the advent of larger gene panels and next generation sequencing.
“Our clinical and research community is proud that so many of our colleagues will be presenting and involved in ASCO 2015,” said Benjamin G. Neel, MD, PhD, Director of the Perlmutter Cancer Center at NYU Langone. “What is most impressive is that our research covers a diverse array of topics, all of them critical areas in which we hope to lead further research into improving diagnosis, treatment and outcomes.”