The 65+ Lymphoma Research Team


One of our greatest challenges in oncology is to identify and administer effective therapy for lymphoma with the least amount of toxicity. Essential to this charge is the need for effective tools capable of both predicting and mitigating toxicity in our patients. These tools are most sorely needed for the majority of lymphoma patients who are older than 60 years at the time of diagnosis.

Our team recognizes that older patients with lymphoma have a complex set of needs, distinct in many ways from the younger patient, and that these patients can benefit from a comprehensive geriatric lymphoma program.

Our goals are to understand how lymphoma biology differs with the aging process, to develop risk-adapted and specific clinical trials with new therapies specifically for older patients, and to understand predictors of toxicity so that we may develop safer and less toxic treatment programs.

For these reasons, we have opened a phase II trial, Comprehensive Geriatric Assessment (GA) to Predict Toxic Events in Older Patients with non-Hodgkin Lymphoma with Imbedded Pilot Study of Pre-Phase Therapy. This research program will prospectively investigate the ability for a self-administered geriatric assessment to predict toxicity in non-Hodgkin lymphoma (NHL) patients ages 60 years or older who are receiving chemotherapy or chemoimmunotherapy.

Two Geriatric Assessment Instruments

The assessment tool encompasses two geriatric assessment (GA) instruments that predict chemotherapy-induced toxicity in solid tumors.

A GA was developed in conjunction with the Cancer and Aging Research Group and the Chemotherapy Risk Assessment Scale for High-Age Patients score.

Additionally, we will use Memorial Sloan Kettering’s Webcore technology, which allows for the seamless electronic capture of data in the MSKCC Innovation Center at 64th Street. This approach should facilitate data handling and analysis, and anticipates a future in which electronic data collection of this type is integrated into our standard of care.

The study will enroll 200 patients throughout the Memorial Sloan Kettering network and will serially capture toxicity data and dynamic changes in the patient’s multidimensional health status with the assessment tool. The goal is to identify factors most predictive of chemotherapy-associated toxicity. A successful tool will then be employed preemptively in future studies to modify therapy before toxicity occurs and improve safety and, ideally, effectiveness. It is anticipated that the study will accrue over the next two to three years.

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Pilot Phase

An important pilot study included in the larger study will evaluate the effect of a low-dose initial treatment (coined “pre-phase therapy”) with rituximab and prednisone prior to the initiation of standard combination chemoimmunotherapy in a subset of patients with diffuse large B cell lymphoma (DLBCL) who are at least 70 years old or who have impaired performance status.

The impact of this initial treatment on the GA and its impact on levels of certain inflammatory markers will both be measured. In a German DLBCL study, pre-phase therapy was able to reduce treatment-related mortality by 50 percent. The approach has not been prospectively studied in the United States, however.

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Part of the 65+ Lymphoma Clinical Trial Program

This effort is part of a robust 65+ lymphoma clinical trial program, which I lead as clinical director of the lymphoma outpatient unit. The program includes various clinical trials for older lymphoma patients with newly diagnosed diffuse large B cell lymphoma, Hodgkin lymphoma, or mantle cell lymphoma.

They include:

  • A Phase III, Open-label, Multicenter, Randomized Study of Sequential Zevalin (Y-90 ibritumomab tiuxetan) versus Observation in Patients at Least 60 Years of Age with Newly Diagnosed Diffuse Large B-cell Lymphoma in PET-negative Complete Remission After R-CHOP or R-CHOP-like Therapy (ZEAL)
    • Following complete response (CR) to front-line anthracycline-based therapy, DLBCL patients are typically observed without further treatment, as no treatment to date has shown overall survival (OS) or progression-free survival (PFS) benefit in a randomized study. Maintenance rituximab has been investigated in this setting but has failed to show PFS benefit in three randomized studies. More than 31 percent of patients in CR after R-CHOP will ultimately die of recurrent lymphoma. Hence, improvements in care are needed. Key endpoints of the study are overall and progression-free survival. Six phase II studies with Y-90 ibritumomab tiuxetan in this setting have shown promising PFS results with low levels of toxicity. The single-dose treatment is attractive to older patients for its short duration and simplicity.
    • The study at our center evaluates one dose of radioimmunotherapy (Y-90 ibritumomab tiuxetan) against the standard of care (observation). Eligible patients have newly diagnosed DLBCL or FL Grade 3B, are age 60 or older, and must have PET-negative CR after R-CHOP or comparable anthracycline-based chemotherapy. Study medication and procedures, as well as the PET scan required to qualify for study entry (if not already performed at your treating center), may be paid for by the study.
    • Following a six-month period during which study medication and any toxicities are evaluated, study patients may return to the referring clinic for standard surveillance of relapse and overall survival.

At the end of the day, all of these exciting developments are fueled by a passion and desire to improve the tolerability and curability of lymphoma for the older patient.

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