A recent study found the combination therapy of thalidomide (Thalomid) and dexamethasone (Decadron), commonly referred to as TD, to be safe and effective as induction therapy in newly diagnosed multiple myeloma patients with impaired kidney function. The study authors also found that 55 percent of participants achieved normal kidney function after TD treatment. The study results were published in the journal Biology of Blood and Marrow Transplantation.

Impaired kidney function is a serious complication that occurs in approximately 20 to 30 percent of myeloma patients at diagnosis and in more than 50 percent of patients with advanced disease. In addition, approximately 9 percent of newly diagnosed myeloma patients suffer from severe kidney failure and require dialysis treatment to remove excess water and waste products from the blood (see related Beacon news).

The selection of an induction therapy for newly diagnosed patients with impaired kidney function is a critical decision, as a rapidly effective treatment that does not impact the kidneys can improve kidney function in a significant number of cases. One of the most common induction therapies for newly diagnosed patients with impaired kidney function is vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD).

However, recent studies have indicated that TD induces superior response rates than VAD. Additionally, the body breaks down and removes thalidomide without involving the kidneys, which makes thalidomide an acceptable form of treatment for patients with impaired kidney function. Revlimid (lenalidomide), by comparison, is excreted in significant quantities by the kidneys. Patients with kidney failure are at an increased risk of toxic reactions if treated with Revlimid (see related Beacon news).

The study investigated the effectiveness of TD as an induction therapy before autologous stem cell transplantation in 31 patients with newly diagnosed myeloma and impaired kidney function. Kidney function is assessed by determining how quickly the kidneys filter creatinine, a waste product produced by the muscles. In this study, researchers defined impaired kidney function as creatinine clearance of less than 50 mL/minute.

Patients received 4 monthly cycles of thalidomide (100 mg/day for 2 weeks and 200 mg/day thereafter) and dexamethasone (40 mg/day on days 1-4, 9-12, and 17-20 on odd cycles and on days 1-4 on even cycles). Patients also received low-dose warfarin (Coumadin) to prevent deep vein blood clotting. Following induction therapy, patients received either a single or a double autologous stem cell transplant with high-dose melphalan (Alkeran).

The authors of the study reported that 23 patients (74 percent) achieved at least a partial response to the treatment, including three (10 percent) who achieved a complete response and five (16 percent) who achieved a very good partial response.

Researchers found that 17 patients (55 percent) achieved normal kidney function after TD treatment, defined as a creatinine clearance of more than 50 mL/minute. Five patients (16 percent) showed improved kidney function (creatinine clearance of 30 - 50 mL/minute); however, for nine patients, kidney function remained seriously impaired (creatinine clearance of less than 30 mL/minute). Researchers observed that patients who recovered from impaired kidney function had less severe kidney failure at diagnosis.

Researchers also found that a better response to TD therapy was related to a higher probability of obtaining normal kidney function. Of the 23 patients who showed at least a partial response to TD, 19 (83 percent) experienced improved kidney function, with 15 (65 percent) achieving normal kidney function. Of the eight patients whose myeloma did not partially respond, only three (38 percent) showed improved kidney function, with two patients (25 percent) achieving normal kidney function.

The most common side effects reported in the study included deep vein blood clotting (10 percent), extensive skin rash (3 percent), mild pain and numbness in the hands and feet (10 percent), constipation (6 percent), and fatigue (3 percent). These side effects were comparable to those observed in patients with normal kidney function.

Of the 22 patients who successfully underwent stem cell collection in preparation for stem cell transplantation, 15 received a double transplant and seven received a single transplant. Patients only received a single transplant because of either inadequate stem cell collection (five patients) or delayed recovery from the first transplant (two patients).

At a median follow-up time of 32 months, the overall median event-free survival was 30 months. There was no significant difference in response rates or median event-free survival between patients undergoing single and double transplants because of the small number of patients.

Based on the results, the authors of the study concluded that TD is an effective and safe induction treatment for patients with newly diagnosed myeloma and impaired kidney function. The observed response rates were comparable to those previously reported in patients with normal kidney function.

The researchers acknowledged that the addition of Velcade (bortezomib) [VTD] might improve treatment by increasing the speed and the rate of response. Although preliminary results from a randomized clinical trial have suggested that the VTD is more effective at inducing complete responses than TD, it is possible that the side effects of pain and numbness in the hands and feet (known as peripheral neuropathy) may worsen with the addition of Velcade.

For more information, please see the study in Biology of Blood and Marrow Transplantation (abstract).