Yesterday, the FDA announced approval for ibrutinib, or Imbruvica in the treatment of patients with mantle cell lymphoma (MCL), who have previously received at least one other therapy. According to the FDA press release:
“Imbruvica is intended for patients with MCL who have received at least one prior therapy. It works by inhibiting the enzyme needed by the cancer to multiply and spread. Imbruvica is the third drug approved to treat MCL. Velcade (2006) and Revlimid (2013) are also approved to treat the disease.”
“Imbruvica’s approval demonstrates the FDA’s commitment to making treatments available to patients with rare diseases,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The agency worked cooperatively with the companies to expedite the drug’s development, review and approval, reflecting the promise of the Breakthrough Therapy Designation program.”
“Imbruvica is the second drug with breakthrough therapy designation to receive FDA approval. The Food and Drug Administration Safety and Innovation Act, passed in July 2012, gave the FDA the ability to designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases.”
“The FDA is approving Imbruvica under the agency’s accelerated approval program, which allows the FDA to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. The FDA also granted Imbruvica priority review and orphan-product designation because the drug demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition and is intended to treat a rare disease, respectively.”
The physicians in the Lymphoma Program at Weill Cornell Medical College are happy to have had the opportunity to be part of this important study, and would like to thank all the patients who participated in the trials. Further information on trials involving MCL and/or ibrutinib can be found on our listings of non-Hodgkin lymphoma clinical trials.
While attending iwCLL 2013, Dr. Richard Furman, a nationally recognized CLL clinician and researcher here in the Lymphoma Program, sat down and gave his thoughts on the latest advances in CLL treatment, and how this will effect future patient outcomes.
The discussion can be found here.
BTK is an essential mediator of B-cell receptor signaling in normal and malignant B-cells. Ibrutinib (PCI-32765), an oral inhibitor of BTK, promotes apoptosis and inhibits proliferation, migration and adhesion in CLL cells. Chemoimmunotherapy (CIT) treatment approaches such as fludarabine, cyclophosphamide and rituximab have markedly improved outcomes of younger, fit patients as initial or second-line therapy. Unfortunately, fludarabine-based therapy is less well tolerated in the elderly and carries significant risk of cellular immune suppression, myelosupression, and subsequent myeloid neoplasia. Additionally, virtually all patients eventually relapse after fludarabine-based CIT, leading to the need for effective salvage regimens that induce durable remissions.
Recently, at the biennial international workshop on CLL (iwCLL), in Cologne, Germany, Dr. Richard Furman presented final results from a large (n=116 patients) multi-cohort Phase Ib/II trial of ibrutinib in treatment-naive (TN) or relapsed/refractory (RR) CLL/SLL. Patients demonstrated a high frequency of durable responses extending beyond 24 months in both TN and RR CLL/SLL including those with high-risk genomic features.
Patients who were TN (all age ≥65 years) or RR (≥ 2 prior therapies including a purine analog and with high-risk (HR) (relapsed within 2 years from combination CIT) were treated with ibrutinib at fixed doses of 420mg or 840mg daily until disease progression (PD). The study’s primary objective was to determine the safety and response rates of both dosing regimens. The overall response rates for the TN and RR patients were 84% and 88% respectively. The progression free survival (PFS) estimated at 26 months for the 85 RR patients is 74% and for the 31 TN patients is 96%. Estimated 26 month overall survival (OS) for 85 RR patients is 78% and for the 31 TN patients is 97%. Median duration of response, PFS, and OS have not been reached at the time of this analysis.
In conclusion, Ibrutinib monotherapy was found to be highly active, well tolerated, and induced durable responses in CLL patients with high-risk disease, R/R patients, and older TN patients. At present there are ongoing randomized trials comparing the safety profile of ibrutinib with other CLL therapeutic agents. Ongoing CLL trials at Weill Cornell Medical College can be found here.