Bruce D. Cheson, MD, Professor of Medicine, Head of Hematology, Deputy Chief, Division of Hematology/Oncology, Georgetown University Hospital, Lombardi Comprehensive Cancer Center, discusses the phase III GADOLIN study, which looks at the anti-CD20 agent obinutuzumab (Gazyva) and bendamustine compared with bendamustine alone in patients with relapsed indolent non-Hodgkin lymphoma (iNHL).

The combination of obinutuzumab and bendamustine did not improve response compared to bendamustine-alone in iNHL patients, said Cheson. However, progression-free survival (PFS) was significantly prolonged with the addition of obinutuzumab, with approximately 15 months median PFS in the bendamustine-only arm and not yet reached medium PFS after just over 20 months in the combination arm.

There were some dosing imbalances between the two arms, which are important to consider, said Cheson. In the combination arm bendamustine was given at 90 mg/m2 days one and two, while versus 120 mg/m2 days one and two in the single-agent arm. It is not clear whether this dosing variation made a difference in the response rates, but it could be responsible for the lack of improved response in the combination arm, said Cheson.

Videos

Dr. Bruce D. Cheson on Obinutuzumab/ Bendamustine Survival Benefit in iNHL

Bruce D. Cheson, MD, Professor of Medicine, Head of Hematology, Director of Hematology Research, Georgetown Lombardi Comprehensive Cancer Center, describes the Lymphoma Research Foundation (LRF).

The LRF is the largest not-for-profit organization in the U.S. that focuses exclusively on lymphoma and chronic lymphocytic leukemia (CLL) and has raised millions of dollars, Cheson says, to fund research. Cheson often encourages his patients to visit lymphoma.org for all research, educational, and advocacy programs on CLL, follicular lymphoma, Hodgkin lymphoma, and large cell lymphoma.

Bruce D. Cheson, MD, Professor of Medicine, Head of Hematology, Director of Hematology Research, Georgetown Lombardi Comprehensive Cancer Center, describes the Lymphoma Research Foundation.

Dr. Cheson on the Lymphoma Research Foundation

Bruce D. Cheson, MD, Professor of Medicine, Head of Hematology, Director of Hematology Research, Georgetown Lombardi Comprehensive Cancer Center, discusses the investigation of PD-1 targeted agents as treatments for patients with hematologic malignancies.

Antibodies that target PD-1 and PD-L1 are currently being explored in various cancer types. In general, PD-1 operates as a T cell regulator that suppresses T cell function. Inhibiting PD-1 causes augmentation in the T cells, causing them to attack cancer cells.

Several pharmaceutical companies are developing agents that target PD-1 and PD-L1, particularly for patients with Hodgkin's lymphoma, acute leukemia, myelodysplasia, and multiple myeloma. However, at this time Cheson notes, the data in follicular lymphoma are difficult to interpret and clearer evidence of benefit needs to be seen.

Bruce D. Cheson, MD, from the Georgetown Lombardi Comprehensive Cancer Center, discusses the investigation of PD-1 targeted agents as treatments for patients with lymphoma. 

Dr. Cheson on Targeting PD-1 in Hematologic Malignancies

Bruce D. Cheson, MD, Professor of Medicine, Head of Hematology, Director of Hematology Research, Georgetown Lombardi Comprehensive Cancer Center, discusses the diagnosis of patients with follicular lymphoma.

A follicular lymphoma diagnosis often occurs incidentally, Cheson says. Too often, physicians perform a fine-needle aspiration biopsy, an inadequate way of making the diagnosis compared to an incisional or excisional biopsy. Once the diagnosis is made, patients undergo a number of staging procedures: CAT and PET scans as well as bone marrow biopsies to determine disease is in its advanced stage. Cheson says that about 80 to 90% of patients do in fact have advanced stage disease.

A physician will then assign a Follicular Lymphoma International Prognostic Index (FLIPI)&lrm; score by analyzing a patient's nodal areas, LDH, age, stage, and hemoglobin level to determine risk.

Dr. Cheson on the Diagnosis of Follicular Lymphoma

Bruce D. Cheson, MD, Professor of Medicine, Head of Hematology, Director of Hematology Research, Georgetown Lombardi Comprehensive Cancer Center, discusses the prospect of using antibody drug conjugates (ADCs) in non-Hodgkin's lymphomas, including follicular lymphoma.

In phase I trials presented at the 2012 American Society of Hematology Annual Meeting, two ADCs targeting CD22 and CD79b, respectfully, showed single-agent activity in follicular and large cell lymphoma.

An ongoing randomized trial is analyzing the activity of these two agents in combination with rituximab. The study has crossover opportunities, providing information about cross resistance or lack thereof between the two agents, Cheson says. These trials have exciting possibilities and could be the first step to developing a drug similar to the ADC brentuximab in Hodgkin lymphoma.

Bruce D. Cheson, MD, from Georgetown Lombardi Comprehensive Cancer Center, discusses the prospect of using antibody drug conjugates in non-Hodgkin lymphomas, including follicular lymphoma.

Bruce D. Cheson, MD

Articles

Dr. Bruce D. Cheson on Obinutuzumab/ Bendamustine Survival Benefit in iNHL

Dr. Cheson on the Lymphoma Research Foundation

Dr. Cheson on Targeting PD-1 in Hematologic Malignancies

Dr. Cheson on the Diagnosis of Follicular Lymphoma

Dr. Cheson on Novel ADCs in Non-Hodgkin Lymphoma