The Lymphoma Program has published the inaugural issue of the New Developments in Lymphoma Newsletter.
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Tag: Richard Furman MD
Palbociclib Displays Promising Results
Palbociclib (PD 0332991) is generating significant excitement according to an April 6th online article from the New York Times. The article cites the results of a recently reported phase II trial in which women with metastatic breast cancer were randomized to receive letrozole plus palbociclib or letrozole alone. Women receiving the combination had their risk of progression cut in half compared to the group that received letrozole alone. These results come roughly one year after the FDA granted Breakthrough Therapy designation to palbociclib, which may help speed up the drug approval process.
Palbociclib is a highly specific oral drug that binds to and inhibits a specific subtype of enzymes called cyclin-dependent kinases (CDK). The same enzymes are critical to the development and progression of mantle cell lymphoma (MCL). Investigators at Weill Cornell Medical College have been leading the evaluation of palbociclib in MCL. Within the next month, we will open a phase I trial evaluating the combination of palbociclib plus ibrutinib in patients with previously treated MCL. For additional information regarding the upcoming trial or other trials in lymphoma, call Amelyn Rodriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.
Ibrutinib and the Improvement in CLL Patient Care
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.
New Developments in Lymphoma 