How Important is Minimal Residual Disease Negativity in Measuring the Successful Treatment of Chronic Lymphocytic Leukemia

Dr. Richard Furman, M.D.
Dr. Richard Furman, M.D.

Recently the Oncology Times asked Dr. Richard Furman his opinion on whether a complete response (CR) and minimal residual disease (MRD) negativity are still requisites for the successful treatment of CLL patients. MRD refers to the small number of leukemic cells that remain in a patient after treatment and can only be detectable using sensitive techniques. In patients who achieve complete responses, MRD can remain and cause relapse. Dr. Furman believes that while MRD negativity is always preferred, it is not the most important measure of outcomes. He stated,

“The most important part of the debate surrounds survival. From a patient’s perspective,  overall survival is the single most important goal,” Furman said. “If achieving MRD negativity comes at a cost of toxicities, short term or long term, it may not translate into improved survival.”   

The combination of fludarabine, cyclophosphamide, and rituximab (FCR) generates deeper remissions and more MRD negativity than fludarabine and rituximab (FR), but can have an impact upon long term marrow health, leading to 8 percent of patients developing secondary myeloid neoplasias (MDS and AML). We may have 60 percent long-term survival with FCR in mutated CLL patients, but if we are losing 8 percent of patients to bone marrow failure, that has to be considered. Still the long-term effects of FCR chemotherapy are unknown. 

Fortunately, CLL patients have another option with BCR and Bcl2 antagonists that may markedly improve survival. The ideal circumstance for a CLL patient would be to obtain MRD negativity without having any additional toxicities. This is where the novel treatments, including BCR antagonists, BCL2 antagonists, and CAR T cells will hopefully take us. With BCR antagonists, the depth or remission continues to improve with continued therapy. While almost all of the initial responses were partial responses with very few complete responses, over time the number of complete responses has increased. This will hopefully translate into MRD negative responses one day. This is the importance of progression free survival, as these patients who have not progressed, and remain on therapy, have the potential to continue to improve their response.

Improved survival of CLL patients over the past few decades shows an apparent change in the natural history of the disease. But Furman claims the advance in overall survival is related to lead-time bias. “We are diagnosing patients earlier in Binet stage A. There has been an increase in overall survival for patients as a group. By stage, there is no benefit for Binet stage A and B. A benefit is seen for Binet stage C. This may be due to better supportive therapies and novel agents, or to a shift to earlier stage disease at diagnosis,” he said, noting there is a great need for prognostic markers.

The full debate and rest of Dr. Furman’s response can be read on the Oncology Times website.

Dr. Richard Furman on Evaluating the Role of Idelalisib in Treating CLL

In this panel discussion from OncLive, Dr. Richard Furman evaluates the role of idelalisib in the treatment of patients with CLL.

2016 Update in Lymphoma and Myeloma: A Collaboration Across the Americas

April Group Photo
Group photo of conference attendees.

Earlier this month Lymphoma Program clinical and research faculty hosted the 2016 Update in Lymphoma and Myeloma. The program is an interactive series including some didactic lectures on new data, discussion around challenging cases in the new era of targeted lymphoma therapies, and tours of our research labs to help stimulate opportunities for collaboration with a group of Latin American oncologists.

Organized by Dr. Peter Martin the meeting seeks to share experiences in managing complicated lymphomas from oncologists around the world and to form collaborative experiences that may be of mutual benefit to both the series hosts and attendees. During this year’s meeting 25 oncologists from South and Central America flew to New York City to attend. The ultimate goal is to help foster collaboration that will help to improve outcomes for patients all over the world.

Discussing the purpose of the event Dr. Peter Martin said, “We are holding this conference because lymphoma has no borders. Through our work we have developed contacts around the world and we have the opportunity to share our experiences with them to better improve patient care. We hope that they can benefit from our knowledge and experience, and help their patients. We hope to find ways to work with them to gather data and information on patient experiences in other countries, so we can help develop programs that might improve outcomes for all patients.”