In a recently published article, two myeloma experts discussed the role of autologous stem cell transplantation as an initial line of therapy in myeloma patients. The debate centered on the limited evidence supporting stem cell transplants in the context of newer, alternative treatment options.
An autologous stem cell transplant is a procedure in which stem cells are collected from a patient prior to high-dose chemotherapy and later re-infused into the body to replace the cells that were destroyed by chemotherapy.
The results of two randomized trials show that patients who underwent stem cell transplantation had a median improved survival time of 12 months to 18 months compared to patients who received conventional chemotherapy. Based on these findings, stem cell transplantation has become a standard treatment for eligible patients.
However, the role of stem cell transplantation as an initial treatment for multiple myeloma is now in question due to the introduction of novel and commonly used anti-myeloma agents including Revlimid (lenalidomide), thalidomide (Thalomid), and Velcade (bortezomib). Studies have shown that most patients who receive conventional chemotherapy along with combinations of these novel agents demonstrate high responses within a short period of time.
According to Dr. Vincent Rajkumar of the Mayo Clinic in Rochester, Minnesota, stem cell transplantation is one of several available treatment options and the decision to undergo the procedure should be based on the specific needs of the patient.
“Autologous stem cell transplantation is just one of many available [treatment] options, and the decision on the need for stem cell transplantation and its timing must be tailored to meet the needs of the patient. A one-size-fits-all approach is no longer applicable in the disease,” wrote Dr. Rajkumar.
In his opinion, the current data on the outcomes following early stem cell transplantation are not enough to support stem cell transplantation as a default method of initial therapy (see related Beacon news).
On the opposite side of the debate, Dr. Philippe Moreau of University Hospital Hotel-Dieu in Nantes, France, contends that the data currently available support the routine use of stem cell transplantation in the treatment of eligible myeloma patients.
“Autologous stem cell transplantation is a routine procedure and is associated with a mortality rate of less than 2 percent, which is lower than that reported by physicians favoring continuous upfront therapy without stem cell transplantation,” wrote Dr. Moreau.
In his opinion, future studies should concentrate on identifying the patients who would benefit most from this treatment option.
Dr. Rajkumar believes that the evidence conferring a clinical benefit of any procedure is defined by an improvement in overall survival or improved quality of life. Currently, there are many studies that claim results in favor of one method over another based on measures such as complete response or progression-free survival. However, in Dr. Rajkumar’s opinion, these measures are not necessarily indicative of better outcomes as far as the patient and quality of life are concerned.
“As long as overall survival has not been shown to be better with one [treatment] approach over the other, and no validate patient-reported quality of life studies have been done, the decision on what the appropriate timing is should be made based primarily on patient preference, not physician preference,” wrote Dr. Rajkumar.
Dr. Brendan Weiss of the Abramson Cancer Center in Philadelphia who was not involved in the debate, agrees with Dr. Rajkumar’s assessment of measures relevant for outcomes.
“Complete response has not been consistently correlated with overall survival in multiple myeloma. Until we have better biomarkers, clinical benefit should be based on improvements in overall survival and/or quality of life,” said Dr. Weiss.
While Dr. Rajkumar supports the use of stem cell transplantation in clinical trials designed to find an eventual cure for myeloma, he does not believe that the procedure should be used as a default initial treatment for all eligible patients in a clinical setting. This is based on his claim that there is limited work investigating the optimal sequence of therapy involving stem cell transplantation.
According to Dr. Rajkumar, results from the few recent studies comparing early stem cell transplantation to delayed stem cell transplantation show no overall survival benefits that favor either option. However, by delaying stem cell transplantation, he believes patients can extend their time spent leading normal lives.
“A delayed stem cell transplant approach allows a person with newly diagnosed myeloma to live the younger years of their life without feeling like a cancer patient,” wrote Dr. Rajkumar.
Additionally, Dr. Rajkumar believes in tailoring each patient’s course of treatment according to his or her risk factors and needs. While he routinely supports early stem cell transplantation in intermediate-risk patients (characterized by particular chromosomal abnormalities), he offers standard-risk patients a choice between early and delayed stem cell transplantation.
Dr. Moreau, on the other hand, views stem cell transplantation as a routine, cost-effective procedure that will likely remain the standard of care for eligible myeloma patients.
“The argument of cost does not support the use of continuous novel agent-based therapy upfront in comparison with early stem cell transplantation, which is less expensive than two years of therapy,” he wrote.
He notes preliminary data from a recent study that appears to favor early stem cell transplantation over standard chemotherapy in combination with novel agents. However, the overall survival was not significantly different between the patient groups, and final results have not yet been published.
While not against the idea of limiting stem cell transplantation to a specified group of patients, Dr. Moreau asserts that the relationship between individual risk factors and the most beneficial treatment options have not yet been adequately identified. Thus, the best approach would be to offer the most effective treatment for all patients, regardless of their risk level.
“Although we are progressing towards a consensus regarding the definition of high-risk disease, no cooperative group is currently able to propose a risk-adapted strategy based on well-defined biological and/or clinical characteristics,” wrote Dr. Moreau.
Dr. Weiss agrees with Dr. Moreau that risk-adapted approaches have not yet been confirmed in clinical trials.
“Unlike the case in acute leukemias, we have not performed appropriate clinical trials to validate risk-adapted approaches, as suggested by the Mayo Clinic. Until these studies are performed, these biomarkers of risk are important in informing discussions of prognosis with patients, analyzing current clinical trials, and generating hypotheses to test in future trials,” added Dr. Weiss.
Additionally, Dr. Moreau argues that in delaying stem cell transplantation, a patient could run the risk of not being able to receive a transplant at all due to disease progression or additional health complications. He references a study in which only 77 percent of patients in a delayed stem cell transplantation group could actually receive a transplant by the time they relapsed.
Dr. Moreau added that ongoing trials evaluating the role of stem cell transplantation in the context of the current understanding of myeloma will hopefully surface with results in the near future.
For more information, please see the article in Leukemia Research (abstract).
By Virginia Li
Source: The Myeloma Beacon