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Fall 2005 Volume 6, Issue 6:
Insights into New Myeloma Tx: Revlimid Study Tops List of Investigations that may Benefit Patients
By Ruben Niesvizky, MD
Recently, the Myeloma Program at New York-Presbyterian Hospital/Weill Cornell Medical Center has generated a considerable amount of excitement by launching a study evaluating a combination regimen, known as BiRD, that includes the antibiotic Biaxin&r

The Multiple Myeloma Program at New York-Presbyterian Hospital/Weill Cornell Medical Center, one of the largest myeloma programs in the United States, is forging ahead with a number of clinical and basic science investigations that may yield promising new treatments for patients. The Multiple Myeloma Program includes a clinical trial of a unique combination regimen including Revlimid® (lenalidomide), a new thalidomide analogue that has already shown promising activity in a variety of hematologic malignancies.

Promising New Treatments

Recently, the Multiple Myeloma Program has generated a considerable amount of excitement by launching a study evaluating a combination regimen, known as BiRD, that includes the antibiotic Biaxin® (clarithromycin), Revlimid, and dexamethasone. The BiRD regimen represents an important next step in the development of new therapeutic regimens for multiple myeloma.

While dexamethasone alone has a response rate of approximately 50%, a protocol called BLTD (Biaxin, low-dose thalidomide, and dexamethasone) has yielded a response rate of 93% and a complete remission rate of 13% in recent clinical studies. The BLTD protocol was pioneered by Dr. Morton Coleman.

These studies, presented at the ASH and ASCO meetings, confirmed the initial observation by Dr. Brian Durie and others that Biaxin contributes to tumor mass reduction in patients with myeloma and Waldenström's macroglobulinemia.

In order to further our understanding of these findings, we recently randomized patients to receive either low-dose thalidomide plus dexamethasone or dexamethasone alone. Patients without a satisfactory response (<50% drop in tumor mass) were started on Biaxin. The figure above illustrates several patients resistant to either T or LTD and how tumor mass significantly declines immediately after the initiation of Biaxin. The addition of Biaxin to this regimen seems to dramatically improve both response rate and time to response, even in patients who were previously unresponsive to D or LTD. Whether this effect is solely a pharmacokinetic effect, or involves other cellular targets, remains to be determined.

While acknowledged to be much more potent than its parent drug, thalidomide, Revlimid avoids many of thalidomide's side effects. We hope that the BiRD combination, by replacing thalidomide with Revlimid, will improve patient safety while maintaining the favorable patient outcomes seen with BLTD. We fully anticipate that Revlimid will achieve an impressive complete remission rate, therefore allowing patients to achieve long-term survival. We have recognized the challenges of the use of this drug alone or in combination and we have observed the benefits of aspirin in preventing serious thrombotic events. We have submitted our data to the upcoming ASH meeting and we will be presenting in a dedicated session.

Multidisciplinary Research Effort

The BiRD study is just one of several ongoing clinical trials in which Multiple Myeloma Program investigators are playing a major role. In particular, our investigators have already initiated a clinical trial of consolidation therapy or second-line treatment for myeloma with dexamethasone plus VELCADE® (bortezomib) for Injection, as preamble for an autologous stem cell transplant. The program at Cornell is one of the first to launch the expanded access protocol for Revlimid in the relapsed setting. Investigators are also evaluating SGN-40, a humanized anti-CD40 monoclonal antibody, and are evaluating a new class of drugs called histone deacetylase inhibitors in three separate protocols. Together, these six protocols cover a wide range of patients.

Our goal is to expand our understanding of myeloma, to improve treatment and, ultimately, to find a cure. In order to do that, we must translate research from the bench to the bedside, and likewise, from the bedside to the bench. We need to investigate treatments for myeloma patients in every stage of the disease. My colleagues include Dr. Selina Chen-Kiang, an immunology and cell cycle expert who is currently focused on elucidating the molecular basis of myeloma, Dr. Roger N. Pearse, expert in the field of cell biology, Dr. Hearn J. Cho, an immunology expert, and Dr. Scott Ely, an expert in pathology. We collaborate with a full team of expert scientists and physicians who meet regularly to share new ideas and communicate findings in multiple myeloma.

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