June 16, 2009 - Emerging Therapies in Leukemia, Lymphoma and Myeloma
- Emerging treatment strategies for adult leukemia, lymphoma and myeloma
- The role of clinical trials in the development of treatments
- How to decide if a clinical trial is right for you
Gail J. Roboz, M.D.
Associate Professor of Medicine
Director, Leukemia Program
Weill Medical College of Cornell
University/New York-Presbyterian Hospital
New York, NY
John P. Leonard, M.D.
Richard T. Silver Distinguished Professor of Hematology and Medical Oncology
Professor of Medicine, Weill Medical College of Cornell University/New York-Presbyterian Hospital
Clinical Director, New York-Cornell Center for Lymphoma and Myeloma
New York, NY
Robert Z. Orlowski, M.D., Ph.D.
Director, Myeloma Section
Associate Professor, Departments of Lymphoma/Myeloma and Experimental Therapeutics
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Drs. Roboz, Leonard and Orlowski discuss the latest developments in the treatment of leukemia, lymphoma and myeloma.
They also talk about clinical trials for blood cancers, including common misconceptions, challenges and the importance of patient participation.
- Patients must be aware of the therapies being studied in clinical trials for their disease. Individuals with a diagnosis of leukemia are advised to discuss the option of participating in a clinical trial with their doctor.
- Participating in a clinical trial doesn't necessarily involve taking an investigational drug or therapy. A clinical trial can include a combination of medications already approved; it can include dose changes and stem cell transplantation. Trials are available for patients who are newly diagnosed, who are already in remission and who have relapsed.
- In the past, the patient's age has been an important eligibility consideration for clinical trial participation. For instance, clinical trials for acute myeloid leukemia (AML) have been generally divided between trials for patients older than 60 years and trials for patients younger than 60 years. Currently, patients' overall health and whether they have other medical problems are considered instead of age alone.
- For acute lymphoblastic leukemia (ALL), great progress has been made in treatment outcomes for children. Unfortunately, the same degree of progress hasn't been made in treatment outcomes for adults with ALL. Some questions doctors are trying to answer in clinical trials for adults with ALL are: Which patients would benefit from a stem cell transplant as part of initial treatment? What types of therapy would prevent the disease from coming back?
- Tremendous progress has been made in the treatment of CML. Still, there are many unanswered questions and many clinical trials trying to address them. For instance, do patients need to stay on oral therapy indefinitely? Which of the three newly approved drugs (Gleevec®, Sprycel® or Tasigna®) should be given first? Is there a benefit in alternating between them during treatment? For patients who aren't responding to one specific therapy, how do doctors decide which one to give next?
- One important question for newly diagnosed patients with chronic lymphocytic leukemia (CLL) and no symptoms is whether to receive treatment right away or wait until symptoms appear. Clinical trials are attempting to answer this question. (Note: Many studies have compared the watch-and-wait approach with an early-treatment approach for people who have low-risk CLL. To date, no benefits of early treatment for people with low-risk CLL have been shown and, as stated, this continues to be an area of study in clinical trials.)
- Doctors are learning how to classify lymphomas more precisely as they learn more about the disease's biology. About 60 different types of lymphoma have been identified to date.
- For indolent (slow-growing) types of lymphoma, such as follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma and chronic lymphocytic leukemia, the standard treatment approach is to try to control the disease for as long as possible with a good quality of life for patients. Much focus in clinical trials is for treatments that can extend remission length and are less toxic than standard therapies. Several drugs are under study in clinical trials for the treatment of indolent and aggressive lymphomas.
- Treanda® (bendamustine) is FDA approved for both the treatment of chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma that has progressed after treatment with Rituxan® (rituximab). This drug is being studied in clinical trials as part of initial treatment for indolent non-Hodgkin lymphomas.
- Velcade® (bortezomib), which is FDA approved for myeloma, is also FDA approved for treating mantle cell lymphoma. It's also being studied in clinical trials for some other types of non-Hodgkin lymphoma. In different studies, Velcade and Treanda are being combined with each other, with Rituxan or with other drugs to see whether they can improve outcomes for patients.
- Revlimid® (lenalidomide) has been studied for treating follicular lymphoma. It's also being studied for treating mantle cell lymphoma and large B-cell lymphoma, both alone and in combination with other drugs.
- Bexxar® (iodine 131-tositumomab) and Zevalin® (yttrium-90-ibritumomab) are radioactive versions of monoclonal antibodies that deliver radiation along with the antibody treatment. These drugs are FDA approved for relapsed or refractory, indolent, follicular or transformed B-cell lymphomas. They're being studied as part of initial therapy for newly diagnosed patients. They're also under study, in combination with other drugs, for treating relapsed disease.
- SGN-35 is a special new monoclonal antibody, like Rituxan, that binds to a different target in the tumor cells. This potential therapy is being studied in clinical trials for the treatment of Hodgkin lymphoma.
- Several clinical trials are under way for vaccine therapies. The idea is to train the patient's immune system to fight the lymphoma by giving a vaccine made from the patient's lymphoma cells. More studies in clinical trials are needed to determine this type of therapy's effectiveness.
- People who have been diagnosed with lymphoma--regardless of the type of lymphoma and whether the disease is newly diagnosed or relapsed--should ask their doctors and become informed about the many clinical trials under way for the disease.
- For patients who need initial therapy, there are many effective combinations, such as Alkeran® (melphalan), prednisone and Thalomid® (thalidomide); Alkeran with prednisone, and Velcade (bortezomib); and Alkeran and prednisone with Revlimid (lenalidomide). For patients who might be transplant candidates, the most commonly used regimens include drug combinations such as Velcade with Thalomid and Decadron® (dexamethasone), and Velcade with Revlimid and Decadron. Some of these combinations have response rates approaching 100 percent. A number of drugs are currently under study or will soon be studied in clinical trials.
- Tanespimycin is a drug that inhibits a target called heat shock protein 90 (Hsp90). This drug is being studied in clinical trials for patients with relapsed and refractory disease.
- CNTO 328, a monoclonal antibody, blocks a protein called interleukin-6 (IL-6). IL-6 is an important factor responsible for the myeloma's growth and drug resistance. This drug is under study in clinical trials.
- Zolinza® (Vorinostat), already FDA approved for treatment of one type of T-cell non-Hodgkin lymphoma, is under study in clinical trials for treating multiple myeloma. This is a new class of drugs called histone deacetylase inhibitors. These drugs change the genes expressed by cancer cells and make them more sensitive to chemotherapy treatment.
- Pomalidomide, a type of immunomodulatory agent, is also under study in clinical trials. Some studies have shown that pomalidomide is effective when combined with low-dose Decadron for patients with relapsed disease, including patients who have received prior treatment with Thalomid or Revlimid.
- Treanda, already FDA approved for treating patients with CLL and relapsed indolent B-cell non-Hodgkin lymphoma, is under study for treatment of multiple myeloma. This drug seems to be effective in patients who have had prior stem cell transplant. It also doesn't cause neuropathy.
- Carfilzomib and NPI-0052F are two drugs under study for patients with relapsed or refractory disease who have been treated with Velcade. These drugs are both in phase I and phase II clinical trials, with very encouraging results.
- Treatments are improving for patients who have myeloma, and recent data suggest that the overall survival has doubled within just the past 10 years.
Questions Asked by the Leukemia, Lymphoma and Myeloma Communities
- How and at what point does the doctor decide to reduce the medication dose if a patient is doing well with a particular medication?
- What other options are available if a myeloma patient develops an allergy to Revlimid (lenalidomide) and cannot take Velcade (bortezomib)?
- What's the association between Rituxan (rituximab) and PML (progressive multifocal leukoencephalopathy)?
- For myeloma, at what point is the disease considered refractory (doesn't respond to treatment)?
- Has there been any recent progress in treating transformed follicular lymphoma?
- Is there a specific drug regimen for a relapsed CLL patient?
- Is the drug Vidaza® (azacitidine), given in combination with Zolinza (vorinostat) for relapsed AML patients, effective for AML patients who have the chromosome defect q7 deletion?
- Will a patient who is responding to treatment for MALT lymphoma need additional treatment or just monitoring?
This program was supported in part by Celgene.