Moderator: Steven M. Horwitz, MD1
Discussants: Alison Moskowitz, MD1; Michelle Fanale, MD2; Andrei Shustov, MD3
From Memorial Sloan Kettering Cancer Center, New York, NY1; MD Anderson Cancer Center, Houston, TX2; University of Washington Medical Center, Seattle, WA3
Address for correspondence: Steven M. Horwitz, MD, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065
E-mail: horwitzs@mskcc.org
DR. HORWITZ: My name is Dr. Steven Horwitz from Memorial Sloan-Kettering Cancer Center. I’m joined today by Drs. Alison Moskowitz, Memorial Sloan-Kettering, Michelle Fanale of MD Anderson, and Andrei Shustov, University of Washington in Seattle. Thank you all for joining us for this conversation on T-cell lymphoma. My colleagues are all well known as experts in T-cell lymphomas. Those of you who treat these diseases recognize the systemic T-cell lymphomas as one of our greater challenges in hematologic malignancies in terms of the treatment options for patients and the frequent lack of definitive data to guide our decisions.
I thought what we would do today is have a very practical discussion about the way we think about these diseases, the decisions we make, and the way we make those decisions. I'll start off by asking when you get a referral of a patient with a new diagnosis of peripheral T-cell lymphoma (PTCL), what are some of the basic things that you first think about in terms of approaching a new patient?
DR. SHUSTOV: I think one of the biggest challenges in T-cell lymphomas still remains making the proper diagnosis. In general, pathologists in the United States have a pretty good idea when they see T-cell lymphomas, however, subclassification remains a challenge even for expert hematopathologists due to frequent histologic overlap between the subtypes of PTCL, and even with non-malignant autoimmune disorders. I frequently see patients who are diagnosed with or misdiagnosed with a different subtype of T-cell lymphoma. The most challenging is differentiation between angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell T-cell lymphoma (ALCL), and PTCL not otherwise specified (PTCL-NOS), especially when the latter patients have high expression of CD30 and/or bear features resembling AITL.
Sometimes they are a slam-dunk diagnosis, but frequently our hematopathologists reverse the diagnosis after doing additional studies on the biopsy material. The most recent case I've seen in my clinic for consultation was a patient with a diagnosis of extranodal NK-cell lymphoma that was reclassified as a gamma-delta T-cell lymphoma after additional work-up. I truly believe that it is advisable that majority, if not all PTCL cases are reviewed by expert hematopathology teams at academic centers that see large volumes of these cases.
I think it's very important to educate community physicians and patients about a proper PTCL diagnosis, especially now that more targeted therapies are being developed and the gene expression profiling techniques will probably lead to identification of specific pathways that are amenable to therapy with specific biologic agents.
DR. FANALE: I'd like to expand upon what Andrei just said. For me the next step after confirming the pathology diagnosis is to think about two things. To think about whether or not this patient is a patient who might be eligible for an ongoing front-line trial, typically if the patient meets eligibility criteria for one of our ongoing front-line trials I would really recommend to the patient to consider being enrolled in that trial, and I also think about whether the patient, if he or she enters into remission with front-line therapy, can be considered for a consolidative autologous stem cell transplant.
I think it's very important to educate community physicians and patients about a proper PTCL diagnosis. Right now, our ongoing front-line trial is the ECHELON-2 trial which is evaluating brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, prednisone (CHP [BV-CHP]) chemotherapy compared to standard of care cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) chemotherapy, and that trial is based on the promising data that we've seen in the initial phase I trial that combined BV plus CHP chemotherapy followed by maintenance BV which demonstrated both high and durable complete remission (CR) rates.1 BV is an antibody drug conjugate that's targeted at CD30 and carries initial US Food and Drug Administration approval for patients who have relapsed or refractory ALCL which has a 100% level of CD30 positivity and then also has a National Comprehensive Cancer Network listing for treating other types of relapsed or refractory CD30 positive PTCL as well.
Also there is another upcoming front-line trial, which is to combine pralatrexate plus CHOP. If a patient isn't eligible for a clinical trial or it's just not feasible for that patient to enroll in a clinical trial, I will then look further at what would be potentially the best standard of care option for that patient.
I'll look at the patient's age and performance status and if they are generally less than age 65 or so and if otherwise well, I'll preferentially treat that patient with CHOEP which is CHOP plus etoposide. And then, for a patient who's either older than this or has multiple other comorbidities, I would treat that patient typically with CHOP alone.