Tag: lymphoma

Obinutuzumab (GA101), a New Generation Rituximab

By Peter Martin, MD

Rituximab is a chimeric (human-mouse) monoclonal antibody directed against the protein CD20 on the surface of B-lymphocytes and most B-cell lymphomas. Several clinical trials have demonstrated that rituximab can increase response rates, prolong remissions, and improve survival among patients with various B-cell lymphomas and is an FDA-approved drug. Interestingly, rituximab was developed during an era when our understanding of how monoclonal antibodies might work was relatively naïve. Obinutuzumab (GA101) is a newer generation anti-CD20 antibody that has undergone significant engineering to capitalize on new knowledge. In preclinical testing, GA101 appeared to work better than rituximab. Three clinical trials evaluating GA101 in patients with follicular lymphoma were presented at the American Society of Hematology (ASH) meeting this year.

Dr. Gilles Salles presented the results of a phase I/II study performed in France, in which patients with indolent non-Hodgkin lymphoma (mostly follicular lymphoma). In phase I of the study, patients were treated with escalating doses of GA101, while in phase 2, patients were randomized between two dose levels (high-dose and low-dose). Most patients had received prior rituximab. Overall, GA101 appeared to be well tolerated, with mild infusion reactions being the most common side effect. The results were encouraging, particularly in the high-dose group, but will need to be confirmed with a larger study and longer follow-up.

Dr. John Radford presented the results of the international GAUDI study, which evaluated the safety and efficacy of combining GA101 with CHOP or FC chemotherapy in patients with previously treated follicular lymphoma. Continue reading “Obinutuzumab (GA101), a New Generation Rituximab”

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.

Weill Cornell Researcher: A Personalized Approach for Targeting Cancer Tumors

Through a collaboration between researchers at Weill Cornell Medical College, Memorial Sloan-Kettering, and the National Cancer Institute, researchers have reported that a tumor-targeting compound called PU-H71 can reveal with great accuracy the set of altered pathways that contribute to malignancy, thus allowing physicians to “fish-out” entire networks of abnormal proteins in tumor cells.

One major obstacle in the fight against cancer is that anticancer drugs often affect normal cells in addition to tumor cells, resulting in significant side effects. Yet research into development of less harmful treatments geared toward the targeting of specific cancer-causing mechanisms is hampered by lack of knowledge of the molecular pathways that drive cancers in individual patients.

“A major goal of cancer research is to replace chemotherapy with drugs that correct specific molecular pathways disrupted by cancer,” said Weill Cornell’s  Dr. Ari Melnick, one of the study’s lead investigator. The research was published in Nature Chemical Biology.

The researchers have uncovered that PU-H71 can reveal, with great accuracy, the set of altered pathways contributing to malignancy, thus allowing physicians to “fish-out” entire networks of abnormal proteins in tumor cells. PU-H71 binds to these abnormal protein complexes which are part of protein networks supporting cancer cell growth, division and survival. This knowledge could lead to more targeted, effective and individualized therapies for the personalized treatment of cancer – a disease in which no two tumors are alike – while producing fewer side effects and ultimately sparing patients from undergoing chemotherapy.

Based on these findings Dr. Melnick and colleagues have received a multi-investigator collaborative grant from the National Cancer Institute in support of clinical trials for the treatment of cancer. Currently, patients are being recruited for the first clinical trial to test the safety of PU-H71 as a drug used for the treatment of a variety of tumors. Subsequent trials will include patients with cancers such as breast, lymphomas, and chemotherapy-resistant leukemia.