Category: Patient Education

Ibrutinib and the Improvement in CLL Patient Care

Furman Face By Dr. Richard Furman MD

Ibrutinib is a first in line of new treatments, known as tyrosine kinase inhibitors that display promise in promoting improved response rates in refractory CLL patients. Unlike chemotherapy which cannot differentiate between healthy and cancerous cells, ibrutinib specifically inhibits the Bruton’s tyrosine kinase (BTK) enzyme in the body’s cancerous B-cells. By inhibiting the enzyme, ibrutinib deprives B-cells of their activating chemical signal. This enzyme is expressed only in B-cells, allowing ibrutinib to exclusively target B-cells, affording a tremendous amount of specificity. This specificity allows for an excellent tolerability of ibrutinib in CLL patients, thus increasing quality of life.

This is significant for CLL patients as chemotherapy treatment often comes with disadvantages. A patient achieving a complete recovery will experience marrow toxicity, and be at risk of developing secondary acute myeloid leukemia and/or myelodysplastic syndrome. Even common CLL regimens like FCR (fludarabine + cyclophosphamide + rituximab), expose patients to major risks.

These initial disadvantages are exacerbated by patient relapse and further chemotherapy. For example a patient, who at diagnosis exhibits a very good response to their first line of chemotherapy treatment and another positive response in their second line of chemotherapy, would ultimately be given a 7-9 year median survival rate from their initial chemotherapy. Unfortunately, survival past that 9 year rate is unlikely, as increased chemotherapy leads to a corresponding decrease in longevity. Any increase in longevity beyond that 9 year mark would require treatment besides standard chemotherapy agents. Accordingly, length of survival is the long term promise and improvement held by tyrosine kinase inhibitors like ibrutinib. The side effects associated with chemotherapy regimens are non-existent for ibrutinib.

Due to the nature of currently available chemotherapy treatment, successful benchmarks are increasingly focused on complete response and partial response rates with chemotherapy, and not on overall survival. Chemotherapy focuses on the complete response, partial response, and minimal residual disease status of patients. Conversely, ibrutinib and other similar treatments display significant improvements towards progression free survival and overall survival, even when accounting for patients who develop resistance and require additional therapy.

Increasingly, the avoidance of chemotherapy is the most important aspect of CLL therapy. My hope is to begin using tyrosine kinase inhibitors like ibrutinib earlier in treatment, and avoid chemotherapy. This would lead to vast improvements in patient quality of life and the important metrics of long term survival.

Dr. Ari Melnick Discusses EZH2 as a Potential Target in Diffuse Large B Cell Lymphoma

Last week Weill Cornell researcher Dr. Ari Melnick sat down with Targeted Oncology to briefly summarize the potential of EZH2 in treating diffuse large B-cell lymphoma.

 

Two Modes of DLBCL Relapse

Yanwen JiangBy Yanwen Jiang PhD 

Despite improvements in care for patients with diffuse large B-cell lymphoma (DLBCL), roughly one-third of patients do not respond to initial therapy or relapse within the first 2-3 years after treatment. Unfortunately, our current understanding of the molecular mechanisms of relapse is extremely poor.

During the recent 2013 American Society of Hematology meeting, we reported for the first time that there exist at least two distinct scenarios of DLBCL relapse.  In the first scenario, the tumor cells at diagnosis are almost genetically identical to tumor cells at relapse. Both tumors harbor the same set of mutations with the relapsed tumor possessing a few additional mutations, suggesting that the relapsed tumor evolved continuously from the tumor present at diagnosis. We termed this scenario “linear” mode.  In the second scenario, the tumors at diagnosis and relapse carry different mutations, suggesting that an early divergent event occurred and that the tumors developed in parallel.  Therefore, we named this scenario the “divergent” mode.  Moreover, we observed that tumors with higher genetic heterogeneity at diagnosis were more likely to relapse through the divergent mode. This may provide a foundation for evaluation of different treatment strategies for different relapse modes.

Currently, we are expanding our study to investigate the role of epigenetics, particularly DNA methylation, in DLBCL relapse.  For more research information on DLBCL, and relapsed DLBCL, please visit our websites at the Elemento Lab and the Melnick lab.