Tag: mantle cell lymphoma

ASCO Update:Bendamustine plus rituximab beats CHOP plus rituximab as first-line treatment for indolent and mantle cell lymphoma

By Peter Martin, MD

At the plenary session of the American Society of Clinical Oncology (ASCO) on Sunday, June 3, Dr. Mattias Rummel from Germany presented updated results from a phase 3 trial initially presented at the American Society of Hematology (ASH) in 2009. The study compared bendamustine plus rituximab (BR) to CHOP chemotherapy plus rituximab (R-CHOP) in over 500 patients with indolent and mantle cell lymphoma.

Now with a median follow-up period of 45 months, the updated data were consistent with the previously reported findings. Bendamustine plus rituximab (BR) was better tolerated than R-CHOP, with significantly less neutropenia, fewer infections, and no alopecia (hair loss), and was also more effective, reducing the risk of progression roughly two-fold.

Importantly, there was no difference in the rate of transformation to aggressive lymphoma, the rate of secondary malignancies, and the ability to collect stem cells. These data support the design of ongoing and planned cooperative group trials further evaluating the first-line use of BR and BR-based combinations.

In his discussion of the abstract, Dr. Michael Williams from the University of Virginia agreed that the data were promising but cautioned that a peer-reviewed publication of the data remains to be seen.

PD0332991 Shows Promising Signs of Activity in Mantle Cell Lymphoma in Phase 1 Trial at Weill Cornell

By Peter Martin, MD

Cancer cells in mantle cell lymphoma (MCL) undergo uncontrolled proliferation due to overproduction of the protein Cyclin D1. The family of proteins called Cyclins combine with enzymes called Cyclin dependent kinases (Cdk) in a way that is analgous to gas in an engine. The Cdks are the engine but they rely on the Cyclins to make them work.

PD0332991 is an orally bioavailable (i.e., a pill) inhibitor of Cdk4/6, the Cdks that combine with Cyclin D1 in MCL. A recently published clinical trial  performed at Weill Cornell Medical College and other sites around the United States demonstrated that PD0332991 could successfully stop MCL tumors from growing in several patients, including one response that lasted for more than 30 months. Biopsies taken from patients while receiving PD0332991 revealed that Cdk4/6 was effectively inhibited while a specialized kind of imaging, called FLT-PET, demonstrated that MCL cells had stopped proliferating. Although these results were promising, not every patient benefited, and the responses were not permanent.

Additional studies combining PD0332991 with other drugs based on promising laboratory data are currently underway at Weill Cornell. Click here for more information.

Update from ASH 2011: New treatments for mantle cell lymphoma are on the horizon

By Peter Martin, MD

Update: this study is closed to enrollment. 

Arguably the most exciting news to come from the American Society of Hematology (ASH) meeting this year was the presentation by Dr. Michael Wang of preliminary results from the phase 2 trial of PCI-32765 for patients with previously treated mantle cell lymphoma (MCL). PCI-32765 is an oral (pill form) inhibitor of an enzyme called Bruton’s Tyrosine Kinase (BTK). BTK plays an important role in communicating pro-survival signals from the cell microenvironment to the nucleus of the cell. Inhibition of BTK by PCI-32765 demonstrated promise in patients with MCL in a national phase 1 that was open at Weill Cornell Medical College. This phase 2 study, also open at Weill Cornell, demonstrated a response rate of approximately 60-70% with little toxicity (mostly mild gastrointestinal side-effects). It is too early to determine how long these effects will last or whether there are any side effects that will become apparent with longer treatment. Click here for more information about this trial.

Dr. Beata Holkova presented the results of a National Cancer Institute (NCI) phase 2 study that was open at several institutions across the country, including Weill Cornell. The trial evaluated the combination of bortezomib (FDA-approved for treatment of patients with previously treated MCL) plus the histone deacetylase inhibitor vorinostat. The combination demonstrated synergistic activity in preclinical studies and showed promised in earlier trials in patients with multiple myeloma. Preliminary results from this NCI trial were encouraging, particularly in the group of patients with MCL that had never been treated with bortezomib. The trial is ongoing. Click here for more information about this study.