Dr. John Leonard Discusses Chimeric Antigen Receptor (CAR) T-cell Therapy for Patients with Advanced B-Cell Lymphoma

In an article from Healio HemOnc Today, Lymphoma Program Director Dr. John Leonard commented on a study presented at the 2016 ASCO meeting, which reported that for patients with advanced B-cell lymphoma, remission could be induced through a combination of low-dose chemotherapy and genetically modified T-cells. These genetically modified T-cells are known as chimeric antigen receptor (CAR) T-cells. They are modified to specifically target the CD-19 proteins found on the surface of B-cells. On the findings of the study he said,

“These represent additional data that show that this treatment regimen has potential in the treatment of patients with resistant, aggressive lymphoma. As far as follow-up is concerned, we need additional studies with larger groups of patients, with longer follow-up periods, to see if these responses are going to be durable.”

Look to this space for additional information on CAR T-cell therapy at Weill Cornell Medicine.

Venetoclax for the Treatment of CLL Patients who have Relapsed after or are Refractory to Ibrutinib/Idelalisib

Picture3

By Richard Furman, M.D.

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.

Acalabrutinib for Patients with Previously Untreated Chronic Lymphocytic Leukemia

Picture3

By Richard Furman, M.D.

Acalabrutinib is a second generation Bruton’s tyrosine kinase (BTK) inhibitor that targets the B-cell receptor signaling and is considered a prime target for the treatment of CLL. Acalabrutinib inhibits BTK activity preventing the activation of the B-cell antigen receptor pathway, and leads to CLL cell death. Recently at the 2016 ASCO annual meeting researchers presented preliminary results from an ongoing phase 1-2 study using acalabrutinib to treat patients with previously untreated CLL. Of the 74 patients enrolled in the trial 72 were evaluable for response. Acalabrutinib was well tolerated, with 72 of 74 patients remaining on treatment at time of analysis and evaluable for response. Neither of the two patients discontinued treatment for drug related adverse events.

The most common side effects were headaches, diarrhea, arthralgia, contusion, nausea, and weight increase, all characterized as mild. Treatment related lymphocytosis occurred in 53% of patients and was resolved in 97% of the affected patients at a median of 7 weeks. Patients who took acalabrutinib experienced a 96% overall response rate (PR=86%, PR-L=10%) with the median time to response being 2-8 months. For patients with untreated CLL the initial safety profile and high response rates are promising. Based on these results a phase 3 trial of acalabrutinib versus ibrutinib has commenced to further study the use of acalabrutinib in the treatment of patients with CLL.