Lymphoma and Myeloma Newsletter - Roswell Park Cancer Institute

NEWSFROMRoswell Park’sLYMPHOMA ANDMYELOMA SERVICE

MEET THE LYMPHOMA & MYELOMA TEAMThe Lymphoma and Myeloma Service at Roswell Park Cancer Institute (RPCI)is dedicated to providing outstanding clinical care, participating in cutting-edgeclinical and laboratory research, and developing more effective treatments for allpatients with the following hematologic malignancies:Non-Hodgkin lymphoma (NHL)Hodgkin lymphoma (HL)Chronic lymphocytic leukemia (CLL)Multiple myeloma (MM) andother plasma cell disorders(e.g., Waldenstron’smacroglobulinemia)The lymphoma andmyeloma team at our Instituteincludes physicians, scientists,hematopathologists, radiologists, radiationoncologists, fellows, nurse practitioners,physician assistants, pharmacists, socialworkers, clinical nurses, research coordinatorsand psychologists working as a cohesive group ofprofessionals dedicated to providingcompassionate and high-quality care for ourpatients and to advancing our understandingand treatment of hematologicmalignancies.Our physicians are active memberson committees in such nationalorganizations as:• The National ComprehensiveCancer Network (NCCN): longtermmonitoring of lymphomapatients participating in theLymphoma Outcomes Database;memberships on individual NHL,HL, and Myeloma TherapyGuidelines Committees• The Alliance for Clinical Trials inOncology (formerly the Cancerand Leukemia Group B (CALGB)national cooperative group)Myron S. Czuczman, MDChief, Lymphoma and Myeloma Service(Department of Medicine)Head, Lymphoma Translational ResearchLaboratory (Departmentof Immunology)Professor, MedicalOncology andHematologyFrancisco J. Hernandez-Ilizaliturri, MDAssociate Professor, Medical Oncologyand Tumor ImmunologySeema Bhat, MDAssistant Professor, Medical Oncologyand HematologyKelvin Lee, MDProfessor, Medical Oncology, Hematologyand Tumor Immunology; Jacobs Family Chairin ImmunologyVishala Neppalli, MDAssistant Professor, PathologyGeorge Deeb, MDAssistant Professor, Pathology and Laboratory MedicineDirector, Hematopathology LaboratoryAssociate Director, Flowand Image CytometryPetr Starostik, MDAssociate Professor, PathologyBora Baysal, MD, PhDAssociate Professor, PathologyAnneMarie Block, PhDAssociate Professor, OncologyDirector, CytogeneticsSheila Jani Sait, PhDAssistant Professor, OncologyPaul Wallace, PhDDirector, Flow & Image CytometryAssociate Professor, PathologyMihai Merzianu, MDAssistant Professor, Pathology2 | 1-800-ROSWELL (1-800-767-9355)

PATHOLOGYA KEY PRIORITYTaking diagnosis to a new levelAt RPCI, a dedicated team of board-certified hematopathologists performs stateof-the-artintegrated diagnostic hematopathology—essential to diagnosing andclassifying hematolymphoid neoplasms according to the most recent WHOclassification.“Pathology is not just looking at cells under the microscope anymore,” saysGeorge Deeb, MD, Assistant Professor, Director of Hematopathology,Department of Pathology & Laboratory Medicine; and Associate Director, Flowand Image Cytometry. “The integrated diagnostic approach is based oncomprehensive clinical, morphologic, immunophenotypic, cytogenetic andmolecular genetic studies of lymph node, bone marrow, blood and otherextranodal and extramedullary tissue samples.”Our hematopathologists work closely with the Lymphoma clinical team and withother ancillary laboratories at RPCI to expedite prompt, comprehensiveassessments. The ancillary laboratories incorporate the following:bone marrow laboratoryimmunohistochemistry laboratory withwide arrays of markers availableflow and image cytometry laboratory withspectrum of comprehensive panels of markersto thoroughly characterize hematolymphoidneoplasms immunophenotypicallycytogenetic laboratory with karyotypic analysisand large number of FISH probes for many typesof genetic abnormalitiesmolecular diagnostic laboratory with a plethoraof PCR and sequencing-based analysesGOING with the FLOWRPCI’s Flow and Image Cytometry Facility—recognizedas one of the nation’s first and finest—analyzes cellsamples for RPCI clinicians and researchers, leadinghealth centers and many National Institutes of Healthclinical studies. This unique facility specializes inleukemias and lymphomas, identifying specific cancertypes and subtypes by determining the specific antigenexpression of the tumor using analyses with antibodiesand sophisticated laser-activated flow cytometry.“This integrated diagnostic approach allows us tocharacterize the tumor’s fingerprint,” says Dr. Deeb,“and provides the most accurate classification that iscritical for planning treatment and predicting therapyresponse and survival.”www.roswellpark.org | 3

it’spersonal:targeting treatmentto each patientIt’s a new era for lymphoma treatment, and it’s an excitingtime to be a part of it, according to Myron Czuczman, MD,Chief, Lymphoma/Myeloma Service and Head, LymphomaTranslational Research Laboratory, Department ofImmunology. The advent of targeted therapies such asmonoclonal antibodies—for example, rituximab, whichtargets a surface protein, CD20, on B-cell lymphomas, CLLand related diseases—have revolutionized the manner inwhich we approach everything from initial diagnosis,pathology, and treatment planning to prognosisassessments. “What has happened,” explains Dr. Czuzcman,“is that we can now examine the cancer cell, not only at itssurface, but also at the molecular level, thanks to specializedPCR cytogenetics and flow cytometric techniques. We canidentify unique molecular characteristics (e.g., expression ofcertain surface proteins, specific pathways that may beupregulated, chromosomal rearrangements or otherdistinguishing molecular features). We are now developingagents that target or attack these particular features of thecancer cell, thereby directing therapy largely to the tumorcell and limiting effects on healthy tissue.”Personalizedmedicinebecomingthe standardIn the past, even with a diagnosis of a specific lymphomatype, a patient would receive the same therapy given for allsubtypes. “We don’t do that anymore,” says Dr. Czuczman.“Now we look at not only the diagnosis, but also themolecular profile of the cancer, which may be very different in two patients with the exact same diagnosis.”The team then determines whether the patient’s cancer has a profile that can be targeted with a drug thatthat works against certain very critical proteins, pathways or molecules in that specific lymphoma. Thesetargeted approaches are more effective against the cancer, and they are less toxic, with fewer side effectsthan standard systemic chemotherapy regimens.For certain patients, adding rituximab to, or substituting it for, some of the more toxic therapies has madea huge impact. RPCI is involved in developing the next generation of these antibodies, like an anti-CD19and/or an anti-CD22. A new anti-CD30 has just been approved. In addition to binding to the intendedtargets, these new agents are also internalized by the cancer cells, making them optimal delivery systemsfor additional cancer-killing agents such as chemotherapy, toxins, or radioactive isotopes.4 | 1-800-ROSWELL (1-800-767-9355)

PROGNOSIS IS PART OFTREATMENT PL ANNINGBloodMarrowANDTransplantTHEP R O G R A MA CENTER OFEXCELLENCEAt RPCI, the Lymphoma and Myeloma team looks at the whole picture whenassessing a patient’s prognosis, including pathology, radiology, staging, symptomsand laboratory values, to predict whether a patient will do well with standard therapyor need more aggressive treatment—from the start. “The best chance of curing apatient is choosing the best and optimal therapy as the first treatment, rather thantrying to salvage with second or subsequent therapies later on,” says Dr. Czuczman.THE RPCI EDGEThe challenge is to choose the appropriate combination of therapies for the specificpatient—a choice based on sound, logical evidence. As a comprehensive cancercenter that’s intimately involved in the research and development of these newtherapies—and determining how best to optimize their benefits—RPCI is uniquelyequipped to meet that challenge for each patient. The aim of understanding eachpatient’s disease is a concerted effort involving surgeons (who do the biopsies) andexperienced hematopathologists, was work with colleagues from Cytogenetics, theLaboratory of Molecular Diagnostics, and the Department of Flow Cytometry, withinvaluable input from the Diagnostic Radiology and Nuclear Medicine departments.The Blood and Marrow Transplant (BMT) Programat RPCI performs approximately 100 to 120blood and marrow transplants each year, treatingpatients with hematologic disorders includingacute and chronic leukemias, aplastic anemia,Hodgkin and non-Hodgkin lymphoma, multiplemyeloma, myelodysplastic syndrome andselected solid tumors.RPCI’s BMT unit was designed for patient safetyand comfort. The unit, and its 14 private patientrooms, are HEPA-filtered to maintain the highestprotection against airborne pathogens. Thenursing staff is specially trained in themanagement and care of immunocompromisedBMT patients and their special needs.www.roswellpark.org | 5

thewayforwardLYMPHOMA AND MYELOMA INTERDISCIPLINARY AND TRANSLATIONAL RESEARCH PROGRAMOur group of clinicians and scientists focuses on studying thebiology of B-cell and T-cell malignancies in an attempt todevelop novel therapeutic strategies and/or biomarkersthat can be used as surrogate markers of response. Usinglaboratory models, we aim to understand how the patient’s immunesystem and biologically designed therapies—monoclonal antibodies,immunomodulatory drugs or small molecules—interact with lymphomacells. The ultimate intent is to design and carry out clinical trials forpatients with lymphoma and multiple myeloma. “Several clinical studiesat our institute are evaluating and testing novel therapeutic strategies inpatients with B-cell or T-cell lymphoma,” says Francisco Hernandez-Ilizaliturri, MD, Associate Professor of Oncology in theLymphoma/Myeloma Service and the Department of Immunology.The Lymphoma Translational Research Laboratory focuses onthree major areas:• Understanding the molecular basis for developing resistance torituximab in patients with B-cell lymphoma• Developing strategies to enhance the anti-tumor activityof rituximab and other monoclonal antibodies against lymphoma,using targeted specific molecules• Identifying of biomarkers of response to currentavailable therapies in patients with B-cell lymphomaAs treatment options for patients with lymphomas and relatedneoplasms become more diverse and complex, it is imperative toidentify and validate biomarkers that can be utilized to predict responseto a given specific therapy. Tailoring the selection of a specific treatmentbased on biomarkers has the potential to increase the percentage ofpatients who will respond to that treatment and who are most likely togain clinical benefit. To date, we have investigated the followingpredictive markers:• Using Han’s algorithm to identify patients with relapsed/refractoryDLBCL most likely to benefit from lenalidomide therapy• MUM-1 expression in patients with newly diagnosed DLBCLtreated with chemo-immunotherapy at our Institute• The prognostic predictive value of functional imaging at the time ofinitial diagnosis in the outcome of patients with follicular lymphoma• CD5 expression as a biomarker of clinical outcome in patients withnewly diagnosed mantle cell lymphoma (MCL) treated at RPCI• IRF-8 expression in DLBCLIn collaboration with the members of the Lymphoma Section and theDepartments of Medicine and Immunology we have been able toestablish a prestigious and scientifically respected LymphomaTranslational Research Program that is actively contributing to the fieldof novel “targeted” therapies of hematologic malignancies and iscapable of advancing “bench” findings into rationally designed clinicaltrials for patients suffering from lymphoma and related neoplasms.Several clinical studies at our Institute areevaluating and testing novel therapeutic strategiesin patients with B-cell or T-cell lymphoma.—Francisco Hernandez-Ilizaliturri, MD6 | 1-800-ROSWELL (1-800-767-9355)

DevelopingstrategiesagainstnewMULTIPLE MYELOMAMultiple myeloma (MM), a cancer ofplasma cells (PC), normally the source ofantibodies that protect against infection, is thesecond most prevalent hematologic malignancy afternon-Hodgkin lymphoma in the United States. Just like their normal PCcounterparts, MM cells are critically dependent on their interactions with normal cells within the bonemarrow (called bone marrow stromal cells (BMSC)) for their survival. Kelvin Lee, MD, Professor ofOncology and Chair, Department of Immunology, and his lab team are investigating the molecular andbiochemical nature of the interaction between myeloma cells and the BMSC, in order to develop a newapproach to attacking myeloma cells—not directly, but through the “soil” in which they grow.The Lee lab was one of the first to recognize that a specific cell surface receptor, called CD28, bestcharacterized in T cells, is essential for myeloma cell survival. The lab’s investigators are now studyingnovel treatment strategies that block the interaction between the CD28 receptor on multiple myelomacells and CD80/CD86 ligands on the pro-survival stromal cells in the bone marrow microenvironment.This approach aims to kill myeloma cells and sensitize the remaining cells to chemotherapy.Dr. Lee is also developing new vaccine strategies against myeloma, using novel vaccines developed andclinically tested by the RPCI Center for Immunotherapy. These are combined with small-molecule agentsthat can reverse the immune system suppression caused by multiple myeloma. “There is evidence thatthe immune system can control multiple myeloma,” says Dr. Lee. “Anti-myeloma vaccines may haveconsiderable promise in early-stage patients, or in patients with a minimal amount of residual disease.”ClinicalPharmacySupportRPCI’s clinical pharmacy specialists work closely with physicians, nurse practitioners andphysician assistants in both inpatient and ambulatory care settings to provide optimalpharmaceutical care to patients. Two clinical pharmacists are dedicated to theLymphoma/Myeloma Service to monitor all therapeutic drugs, provide recommendationsfor growth factor support, antiemetics and pain control, offer medication reviews andpatient discharge counseling, and staff a 24-hour hotline to offer drug information,interaction checks, dosing recommendations for renal and hepatic insufficiencies, and more.www.roswellpark.org | 7