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HCL Combination Therapy: Rituximab and Purine Analog

Panelists: Farhad Ravandi-Kashani, MD, The University of Texas MD Anderson Cancer Center; Robert J. Kreitman, MD, National Institutes of Health
Published: Tuesday, Jul 16, 2019



Transcript:

Robert J. Kreitman, MD: Let’s talk about combination therapy. When would you consider combination therapy using rituximab plus a purine analog? You have worked on this…for…over 10 years.

Farhad Ravandi-Kashani, MD: Rituximab is a humanized monoclonal antibody targeting CD20, and hairy cell leukemia cells do have the highest expression of CD20 among various lymphoid malignancies. Rituximab is now commonly used in various lymphoid neoplasms, including lymphomas and lymphoid leukemias. It was evaluated particularly in the relapsed setting as a single agent in hairy cell leukemia in the early 2000s. There were a few studies that showed the drug—even as a single agent—is active in this disease, can produce responses, including occasionally complete responses. It clearly makes sense to use rituximab in hairy cell. I would like to also add that in many lymphoid leukemias and lymphomas, the single-agent activity of rituximab is almost minimal. But the addition of rituximab to the chemotherapy regimen that’s used for that specific lymphoma or lymphoid malignancy, does improve outcomes significantly. This is what has led to the approval for rituximab for various lymphomas and lymphoid leukemias.

Because of this we decided, as you mentioned, many years ago to combine these 2 drugs, and that’s rituximab and cladribine. We first decided not to do this concurrently, mainly because we felt that cladribine per se on its own can produce very high responses, and in a significant proportion of patients, this would be highly durable. We felt that we did not want to have any form of complications. Because of this, we did sequential therapy, and we gave cladribine. This was followed by 8 weekly doses of rituximab. With that, we have seen and reported that their response rate—complete morphological response rate—is essentially 100%.
 
With the long-term follow-up of these patients, we have had almost no relapses, which clearly is exciting but also somewhat predictable in my opinion. This is because, for example, in a similar disease, chronic lymphocytic leukemia, when rituximab is added to nucleoside analogs, it produces an improvement of responses and duration of responses. Obviously, the question that comes is if concomitant administration of rituximab is better than sequential administration. That means that starting the rituximab while or close to the time you have given the nucleoside analog. The concomitant approach in a case series of patients was published in a study a few years ago, in patients who had relapsed hairy cell, and they showed a very remarkable response rate.

Transcript Edited for Clarity

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Transcript:

Robert J. Kreitman, MD: Let’s talk about combination therapy. When would you consider combination therapy using rituximab plus a purine analog? You have worked on this…for…over 10 years.

Farhad Ravandi-Kashani, MD: Rituximab is a humanized monoclonal antibody targeting CD20, and hairy cell leukemia cells do have the highest expression of CD20 among various lymphoid malignancies. Rituximab is now commonly used in various lymphoid neoplasms, including lymphomas and lymphoid leukemias. It was evaluated particularly in the relapsed setting as a single agent in hairy cell leukemia in the early 2000s. There were a few studies that showed the drug—even as a single agent—is active in this disease, can produce responses, including occasionally complete responses. It clearly makes sense to use rituximab in hairy cell. I would like to also add that in many lymphoid leukemias and lymphomas, the single-agent activity of rituximab is almost minimal. But the addition of rituximab to the chemotherapy regimen that’s used for that specific lymphoma or lymphoid malignancy, does improve outcomes significantly. This is what has led to the approval for rituximab for various lymphomas and lymphoid leukemias.

Because of this we decided, as you mentioned, many years ago to combine these 2 drugs, and that’s rituximab and cladribine. We first decided not to do this concurrently, mainly because we felt that cladribine per se on its own can produce very high responses, and in a significant proportion of patients, this would be highly durable. We felt that we did not want to have any form of complications. Because of this, we did sequential therapy, and we gave cladribine. This was followed by 8 weekly doses of rituximab. With that, we have seen and reported that their response rate—complete morphological response rate—is essentially 100%.
 
With the long-term follow-up of these patients, we have had almost no relapses, which clearly is exciting but also somewhat predictable in my opinion. This is because, for example, in a similar disease, chronic lymphocytic leukemia, when rituximab is added to nucleoside analogs, it produces an improvement of responses and duration of responses. Obviously, the question that comes is if concomitant administration of rituximab is better than sequential administration. That means that starting the rituximab while or close to the time you have given the nucleoside analog. The concomitant approach in a case series of patients was published in a study a few years ago, in patients who had relapsed hairy cell, and they showed a very remarkable response rate.

Transcript Edited for Clarity
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