Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are cancers that affect the lymphocytes in the immune system. Essentially the same disease they are differentiated by the location in the body where they occur. CLL is found in the bloodstream, bone marrow, and sometimes the lymph node and spleen of patients, while SLL occurs in the lymph nodes of patients.
On Wednesday, September 21st at 6pm Director of the CLL Research Center, Dr. Richard Furman will give a presentation on currently available treatment options for patients with CLL/SLL. The presentation will be followed by a Q&A session. This presentation is part of the Lymphoma Research Foundation’s (LRF) “Ask the Doctor” program designed specifically for people affected by lymphoma, and seeks to provide the latest information on treatment. Online registration is available here.
The program includes:
Overview and Treatment Options for Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma – ( CLL / SLL )
Research Updates
Question and Answer Session
This program is free-of-charge and dinner will be provided. Pre-registration is required.
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.
CLL patients who relapse after or are refractory to ibrutinib or idelalisib often have few treatment options and poor outcomes. In an ongoing phase II study, presented at the 2016 annual ASCO meeting, researchers investigated the activity of venetoclax in patients with CLL who have relapsed or become refractory to ibrutinib or idelalisib. Venetoclax (Venclexta, ABT-199), is the first FDA-approves treatment that inhibits the BCL-2 (B-cell lymphoma 2) protein. The BCL-2 protein plays an important role in enabling CLL cells to survive. CLL cells and other lymphomas over express and are more dependent upon BCL-2 protein than normal cells. Therefore, when venetoclax inhibits the protein, the CLL cells die, while the normal cells continue unharmed.
54 patients were enrolled into the two arms of the trial based upon whether they were relapsed or refractory to ibrutinib (Arm A, 38 patients) or idelalisib (Arm B, 10 patients). 48 patients were evaluable for responses. The overall response rate for ibrutinib treated patients was 61% (CR=8%; PR=53%) and for idelalisib was 50% (CR=0%; PR=50%). Side effects were found in less than 20% of patients with the most common including neutropenia, diarrhea, nausea, anemia, fatigue, and hypophosphatemia. These results show that venetoclax displays promising activity for CLL patients who have relapsed or are refractory to both ibrutinib and idelalisib and can be safely administered.
Further research is required to demonstrate the depth and duration of response, but these initial results are positive.
New Developments in Lymphoma 